Publications by authors named "Corradi F"

157 Publications

Role of Negative Pressure Therapy as Damage Control in Soft Tissue Reconstruction for Open Tibial Fractures.

J Reconstr Microsurg 2017 Oct 6;33(S 01):S08-S13. Epub 2017 Oct 6.

Department of Plastic and Reconstructive Surgery, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom.

The concept of damage control orthopaedics (DCO) is a strategy that focuses on managing orthopaedic injuries in polytrauma patients who are in an unstable physiological state. The concept of DCO is an extension of damage control surgery or damage limitation surgery (DCS/DLS). Recently, it has become clear that certain patients, following extensive soft tissue trauma, could benefit from the idea of DCS. In the management of severe lower extremity trauma with exposed fracture sites, aggressive early wound excision debridement, early internal fixation, and vascularized wound coverage within a few days after trauma were proposed. A negative-pressure dressing can be easily and rapidly applied to obtain a temporary closure between surgical stages. While negative pressure wound therapy (NPWT) has clear indications in the management of chronic wounds, its applications in the acute setting in victims of polytrauma are uneven. We conducted a review of the current clinical literature to evaluate the role of NPWT in this field, which points out that the negative pressure, applied immediately after the first debridement, seems to be an optimal bridge to the final reconstruction up to 7 days.
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http://dx.doi.org/10.1055/s-0037-1606542DOI Listing
October 2017

CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells.

Gut 2018 05 7;67(5):903-917. Epub 2017 Apr 7.

Institute of General Pathology, Catholic University and A. Gemelli Polyclinic, Rome, Italy.

Objective: Cancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.

Design: To discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein microarray (RPPA) and cytogenetic analyses, and validated by immunostainings. DNA replication stress (RS) was increased by employing DNA replication-perturbing or polyploidising agents.

Results: The drug-library screening led to the identification of LY2606368 as a potent anti-CSC agent acting in vitro and in vivo in tumour cells from a considerable number of patients (∼36%). By inhibiting checkpoint kinase (CHK)1, LY2606368 affected DNA replication in most CRC-SCs, including RAS-mutated ones, forcing them into premature, lethal mitoses. Parallel genomic, RPPA and cytogenetic analyses indicated that CRC-SCs sensitive to LY2606368 displayed signs of ongoing RS response, including the phosphorylation of RPA32 and ataxia telangiectasia mutated serine/threonine kinase (ATM). This was associated with mutation(s) in and hyperdiploidy, and made these CRC-SCs exquisitely dependent on CHK1 function. Accordingly, experimental increase of RS sensitised resistant CRC-SCs to LY2606368.

Conclusions: LY2606368 selectively eliminates replication-stressed, p53-deficient and hyperdiploid CRC-SCs independently of mutational status. These results provide a strong rationale for biomarker-driven clinical trials with LY2606368 in patients with CRC.
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http://dx.doi.org/10.1136/gutjnl-2016-312623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890648PMC
May 2018

Ultra-low-dose sequential computed tomography for quantitative lung aeration assessment-a translational study.

Intensive Care Med Exp 2017 Dec 4;5(1):19. Epub 2017 Apr 4.

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Largo Rosanna Benzi 8, Genoa, Italy.

Background: Quantitative lung computed tomography (CT) provides fundamental information about lung aeration in critically ill patients. We tested a scanning protocol combining reduced number of CT slices and tube current, comparing quantitative analysis and radiation exposure to conventional CT.

Methods: In pigs, CT scans were performed during breath hold in a model of lung injury with three different protocols: standard spiral with 180 mAs tube current-time product (Spiral180), sequential with 20-mm distance between slices and either 180 mAs (Sequential180) or 50 mAs (Sequential50). Spiral scans of critically ill patients were collected retrospectively, and subsets of equally spaced slices were extracted. The agreement between CT protocols was assessed with Bland-Altman analysis.

Results: In 12 pigs, there was good concordance between the sequential protocols and the spiral scan (all biases ≤1.9%, agreements ≤±6.5%). In Spiral180, Sequential180 and Sequential50, estimated dose exposure was 2.3 (2.1-2.8), 0.21 (0.19-0.26), and 0.09 (0.07-0.10) mSv, respectively (p < 0.001 compared to Spiral180); number of acquired slices was 244 (227-252), 12 (11-13) and 12 (11-13); acquisition time was 7 (6-7), 23 (21-25) and 24 (22-26) s. In 32 critically ill patients, quantitative analysis extrapolated from 1-mm slices interleaved by 20 mm had a good concordance with the analysis performed on the entire spiral scan (all biases <1%, agreements ≤2.2%).

Conclusions: In animal CT data, combining sequential scan and low tube current did not affect significantly the quantitative analysis, with a radiation exposure reduction of 97%, reaching a dose comparable to chest X-ray, but with longer acquisition time. In human CT data, lung aeration analysis could be extrapolated from a subset of thin equally spaced slices.
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http://dx.doi.org/10.1186/s40635-017-0133-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380570PMC
December 2017

A randomized clinical trial of ultrasound-guided infra-clavicular cannulation of the subclavian vein in cardiac surgical patients: short-axis versus long-axis approach.

Intensive Care Med 2017 Nov 13;43(11):1594-1601. Epub 2017 Mar 13.

Anaesthesia and Intensive Care Unit, E.O. Ospedali Galliera, Mura Della Cappuccine 14, 16128, Genoa, Italy.

Purpose: The aim of this study was to compare the success rate and safety of short-axis versus long-axis approaches to ultrasound-guided subclavian vein cannulation.

Methods: A total of 190 patients requiring central venous cannulation following cardiac surgery were randomized to either short-axis or long-axis ultrasound-guided cannulation of the subclavian vein. Each cannulation was performed by anesthesiologists with at least 3 years' experience of ultrasound-guided central vein cannulation (>150 procedures/year, 50% short-axis and 50% long-axis). Success rate, insertion time, number of needle redirections, number of separate skin or vessel punctures, rate of mechanical complications, catheter misplacements, and incidence of central line-associated bloodstream infection were documented for each procedure.

Results: The subclavian vein was successfully cannulated in all 190 patients. The mean insertion time was significantly shorter (p = 0.040) in the short-axis group (69 ± 74 s) than in the long-axis group (98 ± 103 s). The short-axis group was also associated with a higher overall success rate (96 vs. 78%, p < 0.001), first-puncture success rate (86 vs. 67%, p = 0.003), and first-puncture single-pass success rate (72 vs. 48%, p = 0.002), and with fewer needle redirections (0.39 ± 0.88 vs. 0.88 ± 1.15, p = 0.001), skin punctures (1.12 ± 0.38 vs. 1.28 ± 0.54, p = 0.019), and complications (3 vs. 13%, p = 0.028).

Conclusions: The short-axis procedure for ultrasound-guided subclavian cannulation offers advantages over the long-axis approach in cardiac surgery patients.
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http://dx.doi.org/10.1007/s00134-017-4756-6DOI Listing
November 2017

Usefulness of procalcitonin in differentiating Candida and bacterial blood stream infections in critically ill septic patients outside the intensive care unit.

Intern Emerg Med 2017 Aug 4;12(5):629-635. Epub 2017 Feb 4.

Department of Medical Biotechnologies, University of Siena, Siena, Italy.

We aimed to explore the role of procalcitonin (PCT) for the diagnosis of Candida spp. bloodstream infections in a population of critically ill septic patients admitted to internal medicine units. This is a retrospective case-control study considering all cases of candidemia identified in three internal medicine units, from January 1st 2012 to May 31st 2016. For each case of candidemia, two patients with bacteremic sepsis were included in the study as control cases. The end point of the study was to evaluate the diagnostic performance of PCT for the diagnosis of Candida spp. blood stream infections in patients with objectively documented sepsis. Sixty-four patients with candidemia and 128 controls with bacteremia were enrolled. Median and interquartile range (IQR) PCT values are significantly lower in patients with candidemia (0.73; IQR 0.26-1.85 ng/mL) than in those with bacteremia (4.48; IQR 1.10-18.26 ng/mL). At ROC curve analysis, values of PCT greater than 2.5 ng/mL had a negative predictive value (NPV) of 98.3% with an AUC of 0.76 (0.68-0.84 95% CI) for the identification of Candida spp. from blood cultures. At multivariate analysis, a PCT value <2.5 ng/mL showed an odds ratio of 8.57 (95% CI 3.09-23.70; p < 0.0001) for candidemia. In septic patients at risk of Candida infection, a PCT value lower than 2.5 ng/mL should raise the suspicion of candidemia, adding value for considering prompt initiation of antifungal therapy.
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http://dx.doi.org/10.1007/s11739-017-1627-7DOI Listing
August 2017

Molecular Regulation of the Spindle Assembly Checkpoint by Kinases and Phosphatases.

Int Rev Cell Mol Biol 2017 18;328:105-161. Epub 2016 Oct 18.

Regina Elena National Cancer Institute, Rome, Italy; Department of Biology, University of Rome "Tor Vergata", Rome, Italy. Electronic address:

The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC. In such a complex network, some kinases act at the apex of the SAC cascade by either generating (monopolar spindle 1, MPS1/TTK and likely polo-like kinase 1, PLK1), or contributing to generate (Aurora kinase B) kinetochore phospho-docking sites for the hierarchical recruitment of the SAC proteins. Aurora kinase B, MPS1 and budding uninhibited by benzimidazoles 1 (BUB1) also promote sister chromatid biorientation by modulating kinetochore microtubule stability. Moreover, MPS1, BUB1, and PLK1 seem to play key roles in APC/C inhibition by mechanisms dependent and/or independent on MCC assembly. The protein phosphatase 1 and 2A (PP1 and PP2A) are recruited to kinetochores to oppose kinase activity. These phosphatases reverse the phosphorylation of kinetochore targets promoting the microtubule attachment stabilization, sister kinetochore biorientation and SAC silencing. The kinase-phosphatase network is crucial as it renders the SAC a dynamic, graded-signaling, high responsive, and robust process thereby ensuring timely anaphase onset and preventing the generation of proneoplastic aneuploidy.
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http://dx.doi.org/10.1016/bs.ircmb.2016.08.004DOI Listing
November 2017

When, Where, and How to Use Ultrasonography in Patients With Chronic Obstructive Pulmonar Disease.

Arch Bronconeumol 2017 05 23;53(5):229-230. Epub 2016 Dec 23.

Dipartimento di Medicina Interna e Specialità Mediche, Università di Genova, Génova, Italia. Electronic address:

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http://dx.doi.org/10.1016/j.arbres.2016.10.019DOI Listing
May 2017

Randomized Evidence for Reduction of Perioperative Mortality: An Updated Consensus Process.

J Cardiothorac Vasc Anesth 2017 Apr 2;31(2):719-730. Epub 2016 Aug 2.

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Objective: Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality.

Design And Setting: A web-based international consensus conference.

Participants: The study comprised 500 clinicians from 61 countries.

Interventions: A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey.

Measurements And Main Results: The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted.

Conclusions: The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality.
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http://dx.doi.org/10.1053/j.jvca.2016.07.017DOI Listing
April 2017

Lung hyperaeration assessment by computed tomography: correction of reconstruction-induced bias.

BMC Anesthesiol 2016 08 24;16(1):67. Epub 2016 Aug 24.

Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.

Background: Computed tomography (CT) reconstruction parameters, such as slice thickness and convolution kernel, significantly affect the quantification of hyperaerated parenchyma (VHYPER%). The aim of this study was to investigate the mathematical relation between VHYPER% calculated at different reconstruction settings, in mechanically ventilated and spontaneously breathing patients with different lung pathology.

Methods: In this retrospective observational study, CT scans of patients of the intensive care unit and emergency department were collected from two CT scanners and analysed with different kernel-thickness combinations (reconstructions): 1.25 mm soft kernel, 5 mm soft kernel, 5 mm sharp kernel in the first scanner; 2.5 mm slice thickness with a smooth (B41s) and a sharp (B70s) kernel on the second scanner. A quantitative analysis was performed with Maluna® to assess lung aeration compartments as percent of total lung volume. CT variables calculated with different reconstructions were compared in pairs, and their mathematical relationship was analysed by using quadratic and power functions.

Results: 43 subjects were included in the present analysis. Image reconstruction parameters influenced all the quantitative CT-derived variables. The most relevant changes occurred in the hyperaerated and normally aerated volume compartments. The application of a power correction formula led to a significant reduction in the bias between VHYPER% estimations (p < 0.001 in all cases). The bias in VHYPER% assessment did not differ between lung pathology nor ventilation mode groups (p > 0.15 in all cases).

Conclusions: Hyperaerated percent volume at different reconstruction settings can be described by a fixed mathematical relationship, independent of lung pathology, ventilation mode, and type of CT scanner.
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http://dx.doi.org/10.1186/s12871-016-0232-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995787PMC
August 2016

Computer-Aided Quantitative Ultrasonography for Detection of Pulmonary Edema in Mechanically Ventilated Cardiac Surgery Patients.

Chest 2016 Sep 26;150(3):640-51. Epub 2016 Apr 26.

Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.

Background: Lung ultrasonography (LUS) has been used for noninvasive detection of pulmonary edema. Semiquantitative LUS visual scores (visual LUS [V-LUS]) based on B lines are moderately correlated with pulmonary capillary wedge pressure (PCWP) and extravascular lung water (EVLW). A new computer-aided quantitative LUS (Q-LUS) analysis has been recently proposed. This study investigated whether Q-LUS better correlates with PCWP and EVLW than V-LUS and to what extent positive end-expiratory pressure (PEEP) affects the assessment of pulmonary edema by Q-LUS or V-LUS.

Methods: Forty-eight mechanically ventilated patients with PEEP of 5 or 10 cm H2O and monitored by PCWP (n = 28) or EVLW (n = 20) were studied.

Results: PCWP was significantly and strongly correlated with Q-LUS gray (Gy) unit value (r(2) = 0.70) but weakly correlated with V-LUS B-line score (r(2) = 0.20). EVLW was significantly and more strongly correlated with Q-LUS Gy unit mean value (r(2) = 0.68) than with V-LUS B-line score (r(2) = 0.34). Q-LUS showed a better diagnostic accuracy than V-LUS for the detection of PCWP >18 mm Hg or EVLW ≥ 10 mL/kg. With 5-cm H2O PEEP, the correlations with PCWP or EVLW were stronger for Q-LUS than V-LUS. With 10-cm H2O PEEP, the correlations with PCWP or EVLW were still significant for Q-LUS but insignificant for V-LUS. Interobserver reproducibility was better for Q-LUS than V-LUS.

Conclusions: Both V-LUS and Q-LUS are acceptable indicators of pulmonary edema in mechanically ventilated patients. However, at high PEEP only Q-LUS provides data that are significantly correlated with PCWP and EVLW. Computer-aided Q-LUS has the advantages of being not only independent of operator perception but also of PEEP.
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http://dx.doi.org/10.1016/j.chest.2016.04.013DOI Listing
September 2016

CPAP Devices for Emergency Prehospital Use: Looking Inside of It-Reply.

Respir Care 2016 May;61(5):719-20

Department of Anesthesia and Intensive Care E.O. Ospedali Galliera Genova, Italy.

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http://dx.doi.org/10.4187/respcare.04782DOI Listing
May 2016

Liquidity crises on different time scales.

Phys Rev E Stat Nonlin Soft Matter Phys 2015 Dec 2;92(6):062802. Epub 2015 Dec 2.

"Sapienza" University of Rome, Rome, Italy.

We present an empirical analysis of the microstructure of financial markets and, in particular, of the static and dynamic properties of liquidity. We find that on relatively large time scales (15 min) large price fluctuations are connected to the failure of the subtle mechanism of compensation between the flows of market and limit orders: in other words, the missed revelation of the latent order book breaks the dynamical equilibrium between the flows, triggering the large price jumps. On smaller time scales (30 s), instead, the static depletion of the limit order book is an indicator of an intrinsic fragility of the system, which is related to a strongly nonlinear enhancement of the response. In order to quantify this phenomenon we introduce a measure of the liquidity imbalance present in the book and we show that it is correlated to both the sign and the magnitude of the next price movement. These findings provide a quantitative definition of the effective liquidity, which proves to be strongly dependent on the considered time scales.
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http://dx.doi.org/10.1103/PhysRevE.92.062802DOI Listing
December 2015

The classification of hospitalized patients with hyperglycemia and its implication on outcome: results from a prospective observational study in Internal Medicine.

Intern Emerg Med 2016 Aug 26;11(5):649-56. Epub 2015 Nov 26.

Internal and Emergency Medicine Unit, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy.

The relevance of classifying hyperglycemic hospitalized subjects (HS) as known diabetes (D), newly discovered diabetes (ND), and stress hyperglycemia (SH) is unclear. The aim of this study was to determine the prevalence, in-hospital mortality, and length of stay (LOS) of three different phenotypes of HS. Fasting glucose ≥126 mg/dL (7 mmol/L) or random blood glucose ≥200 mg/dL (11.1 mmol/L) defined HS who were categorized into three groups: D; ND (no history of diabetes and HbA1c ≥48 mmol/mol); SH (no history of diabetes and HbA1c <48 mmol/mol). The end points of the study were in-hospital mortality and LOS. Of 1447 consecutive enrolled subjects, the prevalence of HS was 28.6 % (415/1447), of these 71.6 % had D, 21.2 % SH, and 7.2 % ND, respectively. In-hospital death was 3.9 % in normoglycemic and 6.0 % in hyperglycemic subjects. Individuals with SH had an increased risk of in-hospital death (7.9 %) (HR 2.17, 95 % CI 1.18-4.9; p = 0.039), while this was not observed for D and ND patients. The mean LOS was greater in ND and SH subjects. Hyperglycemia is common, and is associated with an increased risk of in-hospital mortality and extension of hospital stay. HbA1c along with clinical history is a useful tool to identify subgroups of hyperglycemic hospitalized subjects. Individuals with SH have a longer LOS, and a double risk of in-hospital mortality. Additionally, identifying previously unknown diabetes represents a remarkable opportunity for prevention of diabetes-related acute and chronic complications.
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http://dx.doi.org/10.1007/s11739-015-1358-6DOI Listing
August 2016

Renal Doppler Resistive Index as a Marker of Oxygen Supply and Demand Mismatch in Postoperative Cardiac Surgery Patients.

Biomed Res Int 2015 29;2015:763940. Epub 2015 Oct 29.

Department of Surgery, University Hospital of Parma, 43100 Parma, Italy.

Background And Objective: Renal Doppler resistive index (RDRI) is a noninvasive index considered to reflect renal vascular perfusion. The aim of this study was to identify the independent hemodynamic determinants of RDRI in mechanically ventilated patients after cardiac surgery.

Methods: RDRI was determined in 61 patients by color and pulse Doppler ultrasonography of the interlobar renal arteries. Intermittent thermodilution cardiac output measurements were obtained and blood samples taken from the tip of pulmonary artery catheter to measure hemodynamics and mixed venous oxygen saturation (SvO2).

Results: By univariate analysis, RDRI was significantly correlated with SvO2, oxygen extraction ratio, left ventricular stroke work index, and cardiac index, but not heart rate, central venous pressure, mean artery pressure, pulmonary capillary wedge pressure, systemic vascular resistance index, oxygen delivery index, oxygen consumption index, arterial lactate concentration, and age. However, by multivariate analysis RDRI was significantly correlated with SvO2 only.

Conclusions: The present data suggests that, in mechanically ventilated patients after cardiac surgery, RDRI increases proportionally to the decrease in SvO2, thus reflecting an early vascular response to tissue hypoxia.
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http://dx.doi.org/10.1155/2015/763940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641959PMC
September 2016

A Neuromorphic Event-Based Neural Recording System for Smart Brain-Machine-Interfaces.

IEEE Trans Biomed Circuits Syst 2015 Oct 26;9(5):699-709. Epub 2015 Oct 26.

Neural recording systems are a central component of Brain-Machince Interfaces (BMIs). In most of these systems the emphasis is on faithful reproduction and transmission of the recorded signal to remote systems for further processing or data analysis. Here we follow an alternative approach: we propose a neural recording system that can be directly interfaced locally to neuromorphic spiking neural processing circuits for compressing the large amounts of data recorded, carrying out signal processing and neural computation to extract relevant information, and transmitting only the low-bandwidth outcome of the processing to remote computing or actuating modules. The fabricated system includes a low-noise amplifier, a delta-modulator analog-to-digital converter, and a low-power band-pass filter. The bio-amplifier has a programmable gain of 45-54 dB, with a Root Mean Squared (RMS) input-referred noise level of 2.1 μV, and consumes 90 μW . The band-pass filter and delta-modulator circuits include asynchronous handshaking interface logic compatible with event-based communication protocols. We describe the properties of the neural recording circuits, validating them with experimental measurements, and present system-level application examples, by interfacing these circuits to a reconfigurable neuromorphic processor comprising an array of spiking neurons with plastic and dynamic synapses. The pool of neurons within the neuromorphic processor was configured to implement a recurrent neural network, and to process the events generated by the neural recording system in order to carry out pattern recognition.
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http://dx.doi.org/10.1109/TBCAS.2015.2479256DOI Listing
October 2015

Real time unsupervised learning of visual stimuli in neuromorphic VLSI systems.

Sci Rep 2015 Oct 14;5:14730. Epub 2015 Oct 14.

Department of Technologies and Health, Istituto Superiore di Sanitá, Roma, Italy.

Neuromorphic chips embody computational principles operating in the nervous system, into microelectronic devices. In this domain it is important to identify computational primitives that theory and experiments suggest as generic and reusable cognitive elements. One such element is provided by attractor dynamics in recurrent networks. Point attractors are equilibrium states of the dynamics (up to fluctuations), determined by the synaptic structure of the network; a 'basin' of attraction comprises all initial states leading to a given attractor upon relaxation, hence making attractor dynamics suitable to implement robust associative memory. The initial network state is dictated by the stimulus, and relaxation to the attractor state implements the retrieval of the corresponding memorized prototypical pattern. In a previous work we demonstrated that a neuromorphic recurrent network of spiking neurons and suitably chosen, fixed synapses supports attractor dynamics. Here we focus on learning: activating on-chip synaptic plasticity and using a theory-driven strategy for choosing network parameters, we show that autonomous learning, following repeated presentation of simple visual stimuli, shapes a synaptic connectivity supporting stimulus-selective attractors. Associative memory develops on chip as the result of the coupled stimulus-driven neural activity and ensuing synaptic dynamics, with no artificial separation between learning and retrieval phases.
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http://dx.doi.org/10.1038/srep14730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604465PMC
October 2015

CPAP Devices for Emergency Prehospital Use: A Bench Study.

Respir Care 2015 Dec 29;60(12):1777-85. Epub 2015 Sep 29.

Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Sezione Anestesia e Rianimazione, Università degli Studi di Genova, Genova, Italy. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria San Martino-Istituto Scientifico Tumori, Genova, Italy.

Background: CPAP is frequently used in prehospital and emergency settings. An air-flow output minimum of 60 L/min and a constant positive pressure are 2 important features for a successful CPAP device. Unlike hospital CPAP devices, which require electricity, CPAP devices for ambulance use need only an oxygen source to function. The aim of the study was to evaluate and compare on a bench model the performance of 3 orofacial mask devices (Ventumask, EasyVent, and Boussignac CPAP system) and 2 helmets (Ventukit and EVE Coulisse) used to apply CPAP in the prehospital setting.

Methods: A static test evaluated air-flow output, positive pressure applied, and FIO2 delivered by each device. A dynamic test assessed airway pressure stability during simulated ventilation. Efficiency of devices was compared based on oxygen flow needed to generate a minimum air flow of 60 L/min at each CPAP setting.

Results: The EasyVent and EVE Coulisse devices delivered significantly higher mean air-flow outputs compared with the Ventumask and Ventukit under all CPAP conditions tested. The Boussignac CPAP system never reached an air-flow output of 60 L/min. The EasyVent had significantly lower pressure excursion than the Ventumask at all CPAP levels, and the EVE Coulisse had lower pressure excursion than the Ventukit at 5, 15, and 20 cm H2O, whereas at 10 cm H2O, no significant difference was observed between the 2 devices. Estimated oxygen consumption was lower for the EasyVent and EVE Coulisse compared with the Ventumask and Ventukit.

Conclusions: Air-flow output, pressure applied, FIO2 delivered, device oxygen consumption, and ability to maintain air flow at 60 L/min differed significantly among the CPAP devices tested. Only the EasyVent and EVE Coulisse achieved the required minimum level of air-flow output needed to ensure an effective therapy under all CPAP conditions.
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http://dx.doi.org/10.4187/respcare.04134DOI Listing
December 2015

Simplified PESI score and sex difference in prognosis of acute pulmonary embolism: a brief report from a real life study.

J Thromb Thrombolysis 2016 May;41(4):606-12

Medicina Interna, Ospedale Santa Maria Annunziata, Florence, Italy.

Prognostic stratification of acute pulmonary embolism (PE) remains a challenge in clinical practice. Simplified PESI (sPESI) score is a practical validated score aimed to stratify 30-day mortality risk in acute PE. Whether prognostic value of sPESI score differs according to sex has not been previously investigated. Therefore the aim of our study was to provide information about it. Data records of 452 patients, 180 males (39.8 %) and 272 females (60.2 %) discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. sPESI was retrospectively calculated. Variables enclosed in sPESI score, all cause in-hospital mortality and overall bleedings were compared between sexes. Moreover, predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was tested and compared between sexes. sPESI score 0 (low risk) was found in 17.7 % of males and 13.6 % of females (p = 0.2323). We didn't find significant difference in sPESI scoring distribution. Age ≥80 years (51.4 vs. 33.8 %, p = 0.0003) and heart rate ≥110 bpm (23.5 vs. 14.4 %, p = 0.0219) were found significantly more prevalent in females, whereas active cancer (23.8 vs. 39.4 %, p = 0.0004) and cardio-respiratory diseases (19.8 vs. 27.7 %, p = 0.0416) were in males. All cause in-hospital mortality was 0 % in both genders for sPESI score 0, whereas it was 5.4 % in females and 13.6 % in males with sPESI score 1-2 (p = 0.0208) and 22 % in females and 19.3 % in males with sPESI score ≥3 (p = 0.7776). Overall bleedings were significantly more frequent in females compared with males (4.77 vs. 0.55 %, p = 0.0189). In females overall bleedings ranged from 2.7 % in sPESI score 0 to 6 % in sPESI score ≥3. Predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was higher in females compared to males (AUC 0.72 vs. 0.67, respectively). In real life different co-morbidity burdens in females compared to males. Females seems to be at lower risk of all cause in-hospital mortality for sPESI score ≤2 but at higher risk of bleeding, irrespective from sPESI scoring. Predictive ability of sPESI score seems better in females.
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http://dx.doi.org/10.1007/s11239-015-1260-0DOI Listing
May 2016

A reconfigurable on-line learning spiking neuromorphic processor comprising 256 neurons and 128K synapses.

Front Neurosci 2015 29;9:141. Epub 2015 Apr 29.

Institute of Neuroinformatics, University of Zurich and ETH Zurich Zurich, Switzerland.

Implementing compact, low-power artificial neural processing systems with real-time on-line learning abilities is still an open challenge. In this paper we present a full-custom mixed-signal VLSI device with neuromorphic learning circuits that emulate the biophysics of real spiking neurons and dynamic synapses for exploring the properties of computational neuroscience models and for building brain-inspired computing systems. The proposed architecture allows the on-chip configuration of a wide range of network connectivities, including recurrent and deep networks, with short-term and long-term plasticity. The device comprises 128 K analog synapse and 256 neuron circuits with biologically plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it with on-line learning abilities. In addition to the analog circuits, the device comprises also asynchronous digital logic circuits for setting different synapse and neuron properties as well as different network configurations. This prototype device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4 mm(2), and consumes approximately 4 mW for typical experiments, for example involving attractor networks. Here we describe the details of the overall architecture and of the individual circuits and present experimental results that showcase its potential. By supporting a wide range of cortical-like computational modules comprising plasticity mechanisms, this device will enable the realization of intelligent autonomous systems with on-line learning capabilities.
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http://dx.doi.org/10.3389/fnins.2015.00141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413675PMC
May 2015

Quantitative analysis of lung ultrasonography for the detection of community-acquired pneumonia: a pilot study.

Biomed Res Int 2015 25;2015:868707. Epub 2015 Feb 25.

Department of Internal Medicine and Medical Specialties, University of Genoa, 16100 Genoa, Italy.

Background And Objective: Chest X-ray is recommended for routine use in patients with suspected pneumonia, but its use in emergency settings is limited. In this study, the diagnostic performance of a new method for quantitative analysis of lung ultrasonography was compared with bedside chest X-ray and visual lung ultrasonography for detection of community-acquired pneumonia, using thoracic computed tomography as a gold standard.

Methods: Thirty-two spontaneously breathing patients with suspected community-acquired pneumonia, undergoing computed tomography examination, were consecutively enrolled. Each hemithorax was evaluated for the presence or absence of abnormalities by chest X-ray and quantitative or visual ultrasonography.

Results: Quantitative ultrasonography showed higher sensitivity (93%), specificity (95%), and diagnostic accuracy (94%) than chest X-ray (64%, 80%, and 69%, resp.), visual ultrasonography (68%, 95%, and 77%, resp.), or their combination (77%, 75%, and 77%, resp.).

Conclusions: Quantitative lung ultrasonography was considerably more accurate than either chest X-ray or visual ultrasonography in the diagnosis of community-acquired pneumonia and it may represent a useful first-line approach for confirmation of clinical diagnosis in emergency settings.
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http://dx.doi.org/10.1155/2015/868707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355628PMC
May 2016

Lung Ultrasound-Implemented Diagnosis of Acute Decompensated Heart Failure in the ED: A SIMEU Multicenter Study.

Chest 2015 Jul;148(1):202-210

Background: Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED.

Methods: We conducted a multicenter, prospective cohort study in seven Italian EDs. For patients presenting with acute dyspnea, the emergency physician was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea after (1) the initial clinical assessment and (2) after performing LUS ("LUS-implemented" diagnosis). All patients also underwent chest radiography. After discharge, the cause of each patient's dyspnea was determined by independent review of the entire medical record. The diagnostic accuracy of the different approaches was then compared.

Results: The study enrolled 1,005 patients. The LUS-implemented approach had a significantly higher accuracy (sensitivity, 97% [95% CI, 95%-98.3%]; specificity, 97.4% [95% CI, 95.7%-98.6%]) in differentiating ADHF from noncardiac causes of acute dyspnea than the initial clinical workup (sensitivity, 85.3% [95% CI, 81.8%-88.4%]; specificity, 90% [95% CI, 87.2%-92.4%]), chest radiography alone (sensitivity, 69.5% [95% CI, 65.1%-73.7%]; specificity, 82.1% [95% CI, 78.6%-85.2%]), and natriuretic peptides (sensitivity, 85% [95% CI, 80.3%-89%]; specificity, 61.7% [95% CI, 54.6%-68.3%]; n = 486). Net reclassification index of the LUS-implemented approach compared with standard workup was 19.1%.

Conclusions: The implementation of LUS with the clinical evaluation may improve accuracy of ADHF diagnosis in patients presenting to the ED.

Trial Registry: Clinicaltrials.gov; No.: NCT01287429; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1378/chest.14-2608DOI Listing
July 2015

Towards a neuromorphic vestibular system.

IEEE Trans Biomed Circuits Syst 2014 Oct 9;8(5):669-80. Epub 2014 Oct 9.

The vestibular system plays a crucial role in the sense of balance and spatial orientation in mammals. It is a sensory system that detects both rotational and translational motion of the head, via its semicircular canals and otoliths respectively. In this work, we propose a real-time hardware model of an artificial vestibular system, implemented using a custom neuromorphic Very Large Scale Integration (VLSI) multi-neuron chip interfaced to a commercial Inertial Measurement Unit (IMU). The artificial vestibular system is realized with spiking neurons that reproduce the responses of biological hair cells present in the real semicircular canals and otholitic organs. We demonstrate the real-time performance of the hybrid analog-digital system and characterize its response properties, presenting measurements of a successful encoding of angular velocities as well as linear accelerations. As an application, we realized a novel implementation of a recurrent integrator network capable of keeping track of the current angular position. The experimental results provided validate the hardware implementation via comparisons with a detailed computational neuroscience model. In addition to being an ideal tool for developing bio-inspired robotic technologies, this work provides a basis for developing a complete low-power neuromorphic vestibular system which integrates the hardware model of the neural signal processing pathway described with custom bio-mimetic gyroscopic sensors, exploiting neuromorphic principles in both mechanical and electronic aspects.
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http://dx.doi.org/10.1109/TBCAS.2014.2358493DOI Listing
October 2014

Diagnostic value of chest ultrasound after cardiac surgery: a comparison with chest X-ray and auscultation.

J Cardiothorac Vasc Anesth 2014 Dec 26;28(6):1527-32. Epub 2014 Sep 26.

Department of Surgery, Cardiac Surgery Intensive Care Unit, University Hospital of Parma, Parma; Department of Critical Care, Intensive Care Unit, E.O. Ospedali Galliera, Genova, Italy.

Objective: Chest auscultation and chest x-ray commonly are used to detect postoperative abnormalities and complications in patients admitted to intensive care after cardiac surgery. The aim of the study was to evaluate whether chest ultrasound represents an effective alternative to bedside chest x-ray to identify early postoperative abnormalities.

Design: Diagnostic accuracy of chest auscultation and chest ultrasound were compared in identifying individual abnormalities detected by chest x-ray, considered the reference method.

Setting: Cardiac surgery intensive care unit.

Participants: One hundred fifty-one consecutive adult patients undergoing cardiac surgery.

Interventions: All patients included were studied by chest auscultation, ultrasound, and x-ray upon admission to intensive care after cardiac surgery.

Measurements And Main Results: Six lung pathologic changes and endotracheal tube malposition were found. There was a highly significant correlation between abnormalities detected by chest ultrasound and x-ray (k = 0.90), but a poor correlation between chest auscultation and x-ray abnormalities (k = 0.15).

Conclusions: Chest auscultation may help identify endotracheal tube misplacement and tension pneumothorax but it may miss most major abnormalities. Chest ultrasound represents a valid alternative to chest x-ray to detect most postoperative abnormalities and misplacements.
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http://dx.doi.org/10.1053/j.jvca.2014.04.012DOI Listing
December 2014

Real-time elastography in the assessment of liver fibrosis: a review of qualitative and semi-quantitative methods for elastogram analysis.

Ultrasound Med Biol 2014 Sep 25;40(9):1923-33. Epub 2014 Jun 25.

Department of Radiology, E. O. Ospedali Galliera, Genoa, Italy.

Despite its invasiveness, liver biopsy is still considered the gold standard for the assessment of hepatic fibrosis. Non-invasive ultrasound-based techniques are increasingly employed to assess parenchymal stiffness and the progression of chronic diffuse liver diseases. Real-time elastography is a rapidly evolving technique that can reveal the elastic properties of tissues. This review examines qualitative and semi-quantitative methods developed for analysis of real-time liver elastograms, to estimate parenchymal stiffness and, indirectly, the stage of fibrosis. Qualitative analysis is the most immediate approach for elastogram analysis, but this method increases intra- and inter-observer variability, which is seen as a major limitation of real-time elastography. Semi-quantitative methods include analysis of the histogram derived from color-coded maps, as well as calculation of the elastic ratio and fibrosis index.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2014.03.021DOI Listing
September 2014

Helmet CPAP vs. oxygen therapy in severe hypoxemic respiratory failure due to pneumonia.

Intensive Care Med 2014 Jul 10;40(7):942-9. Epub 2014 May 10.

Emergency Medicine Department, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Purpose: The efficacy of noninvasive continuous positive airway pressure (CPAP) to improve outcomes in severe hypoxemic acute respiratory failure (hARF) due to pneumonia has not been clearly established. The aim of this study was to compare CPAP vs. oxygen therapy to reduce the risk of meeting criteria for endotracheal intubation (ETI).

Methods: In a multicenter randomized controlled trial conducted in four Italian centers patients with severe hARF due to pneumonia were randomized to receive helmet CPAP (CPAP group) or oxygen delivered with a Venturi mask (control group). The primary endpoint was the percentage of patients meeting criteria for ETI, including either one or more major criteria (respiratory arrest, respiratory pauses with unconsciousness, severe hemodynamic instability, intolerance) or at least two minor criteria (reduction of at least 30% of basal PaO2/FiO2 ratio, increase of 20% of PaCO2, worsening of alertness, respiratory distress, SpO2 less than 90%, exhaustion).

Results: Between February 2010 and 2013, 40 patients were randomized to CPAP and 41 to Venturi mask. The proportion of patients meeting ETI criteria in the CPAP group was significantly lower compared to those in the control group (6/40 = 15% vs. 26/41 = 63%, respectively, p < 0.001; relative risk 0.24, 95% CI 0.11-0.51; number needed to treat, 2) two patients were intubated in the CPAP group and one in the control group. The CPAP group showed a faster and greater improvement in oxygenation in comparison to controls (p < 0.001). In either study group, no relevant adverse events were detected.

Conclusions: Helmet CPAP reduces the risk of meeting ETI criteria compared to oxygen therapy in patients with severe hARF due to pneumonia.
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http://dx.doi.org/10.1007/s00134-014-3325-5DOI Listing
July 2014

Contrast-enhanced ultrasound to determine correct central venous catheter position.

Am J Emerg Med 2014 Jul 4;32(7):809-10. Epub 2014 Feb 4.

Dipartimento di Anestesia e Rianimazione, E.O. Ospedali Galliera, Genova, Italy.

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http://dx.doi.org/10.1016/j.ajem.2014.01.033DOI Listing
July 2014

Ranolazine in the prevention of anthracycline cardiotoxicity.

Pharmacol Res 2014 Jan 21;79:88-102. Epub 2013 Nov 21.

Institute of Cardiology and Center of Excellence on Aging (Ce.S.I.), "G. d'Annunzio" University, Chieti, Italy; G. Monasterio Foundation, Pisa, Italy. Electronic address:

Ranolazine is a selective inhibitor of the cardiomyocyte late inward sodium current, INaL, and features anti-ischemic, antiarrhythmic and ATP-sparing actions. Extensive laboratory data show that anthracyclines can induce the production of reactive oxygen species (ROS). Other laboratory data show that ROS can hyperactivate the cardiac isoform of calmodulin-dependent protein kinase II (CaMKII δ), in turn inducing a hyperactivation of the cardiac late sodium current (INaL) and a resulting cytosolic calcium overload. This, as a consequence of the related sodium overload, can induce a mitochondrial calcium depletion that, in turn, triggers a chronic vicious cycle characterized by mitochondrial H2O2 production (increased oxidative stress), and NAD(P)H and ATP depletion (energetic stress), both sustaining ROS production. We hypothesize that anthracyclines may induce both INaL hyperactivation and an oxidative/energetic vicious cycle in cardiomyocytes. These sustained oxidative and energetic stresses may induce low-level cardiomyocyte and cardiac stem cell death by various mechanisms, leading to heart failure in the presence of genetic factors, age, ischemic and arrhythmic events, harmful dietary behaviors, and concomitant diseases. By reducing INaL in a myocardium particularly vulnerable to apoptotic stress and ischemia ranolazine might thus exert cardioprotection interfering with the vicious cycle of anthracycline cardiotoxicity.
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http://dx.doi.org/10.1016/j.phrs.2013.11.001DOI Listing
January 2014

Chest ultrasound in acute respiratory distress syndrome.

Curr Opin Crit Care 2014 Feb;20(1):98-103

aDipartimento Cardio-Nefro-Polmonare, Sezione Terapia Intensiva Cardiochirurgica, Azienda Ospedaliero Universitaria di Parma, Parma bDipartimento di Anestesia e Rianimazione, E.O. Ospedali Galliera cDipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Sezione Anestesia e Rianimazione, Università degli Studi di Genova, IRCCS AOU San Martino, IST, Genova, Italy.

Purpose Of Review: This review discusses the role of chest ultrasound in diagnosis and management of acute respiratory distress syndrome (ARDS) and the most recent technical progresses in this field.

Recent Findings: Clinically, suspected ARDS can be easily confirmed by lung ultrasonography through the recognition of a typical pattern characterized by B-lines, spared areas, pleural line thickening, and subpleural consolidations. A visual score based on number and thickness of B-lines permits a semiquantitative evaluation of the amount of extravascular lung water and lung density. Recently, a quantitative lung ultrasound method has been proposed. The heart may be also involved in ARDS either primarily or by the application of positive pressure ventilation. The incidence of acute cor pulmonale during ARDS is, even if under protective ventilation, not negligible. The use of echocardiography combined with lung ultrasound is important for early detection of cor pulmonale, identification of the best ventilator strategy to preserve heart-to-lung interaction, and prediction of weaning success.

Summary: An ultrasound-integrated approach combining lung ultrasound and echocardiography should be recommended as a suitable technique to manage ARDS during diagnosis, mechanical ventilation setting, and weaning.
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http://dx.doi.org/10.1097/MCC.0000000000000042DOI Listing
February 2014
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