Search

Francesca Innocenti, Cristian Lazzari, Francesca Ricci, Elisa Paolucci, Ilya Agishev, Riccardo Pini Emergency Department High-Dependency Unit, Department of Clinical and Experimental Medicine, Careggi University Hospital, Florence, ItalyCorrespondence: Francesca Innocenti Lg. Brambilla 4, Florence, 50144, ItalyTel +39 333 9117845Email innocenti.fra66@gmail.comAbstract: In the Emergency Medicine setting, D-dimer is currently employed in the diagnostic assessment of suspected venous thromboembolism and aortic syndrome. The nonspecific symptoms reported by patients, like chest pain, dyspnea or syncope, uncover a wide range of differential diagnosis, spanning from mild to life-threatening conditions. Therefore, we assumed the perspective of the Emergency Physician and, in this narrative review, we reported a brief presentation of the epidemiology of these symptoms and the characteristics of patients, in whom we could suspect the aforementioned pathologies. We also reported in which patients D-dimer gives useful information. In fact, when the probability of the disease is high, the D-dimer level is futile. On the contrary, given the low specificity of the test, when the probability of the disease is very low, a false-positive value of the D-dimer only increases the risk of overtesting. Patients with low to moderate probability really benefit from the D-dimer testing, in order to prevent the execution of expensive and potentially dangerous imaging tests. In the second part of the review, we focused on the prognostic value of the test in septic patients. The early prognostic stratification of septic patients remains a challenge for the Emergency Physician, in the absence of a definite biomarker or score to rely on. Therefore, we need several parameters for the early identification of patients at risk of an adverse prognosis and the D-dimer may play a role in this demanding task. SARS COVID-19 patients represent an emerging reality, where the role of the D-dimer for prognostic stratification could be relevant. In fact, in patients with severe forms of this disease, the D-dimer reaches very high values, which appear to parallel the course of respiratory failure. Whether the test may add useful information for the management of these patients remains to be determined.Keywords: venous thromboembolism, aortic syndromes, diagnostic assessment, sepsis, COVID-19, prognostic stratification

Marco Massafra,1,* Maria Ilenia Passalacqua,1,* Vittorio Gebbia,2,3 Paolo Macrì,4 Chiara Lazzari,5 Vanesa Gregorc,5 Carmelo Buda,1 Giuseppe Altavilla,1 Mariacarmela Santarpia1 1Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, Messina, Italy; 2Medical Oncology and Supportive Care Unit, La Maddalena Cancer Center, Palermo, Italy; 3Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; 4Thoracic Surgery Unit, Humanitas Istituto Clinico Catanese, Catania, Italy; 5Department of Oncology, Università Vita-Salute, IRCCS-Ospedale San Raffaele, Milano, Italy*These authors contributed equally to this workCorrespondence: Mariacarmela SantarpiaMedical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, via Consolare Valeria, 1, Messina, 98125, ItalyEmail mariacarmela.santarpia@unime.itAbstract: Immunotherapy with antibodies against PD-1 or PD-L1, either alone or in combination with chemotherapy, has revolutionized treatment paradigms of non-small cell lung cancer (NSCLC) patients without oncogenic driver alterations. These agents, namely immune checkpoint inhibitors (ICIs), have also widely demonstrated a remarkable efficacy in locally advanced as well as in early-stage NSCLC. Assessment of tumor PD-L1 expression by immunohistochemistry has entered into routine clinical practice to select patients for immunotherapy, even though its predictive role has long been debated. Despite improved survival outcomes over standard chemotherapy, treatment with ICIs is associated with initial low response rate, with a significant proportion of patients not responding to these agents. Hence, novel appealing predictive biomarkers, such as those related to tumor cell signaling pathways, metabolism or the tumor microenvironment, have emerged as potentially useful to select those patients most likely to benefit from immunotherapy. Moreover, most patients ultimately develop acquired resistance to ICI treatment over time and novel therapeutic strategies are urgently needed to overcome or delay resistance. Herein, we provide an overview on recent advances in immunotherapy in NSCLC, focusing on updated results from studies on ICIs in different disease settings and at different lines of treatment. We further describe currently emerging predictive biomarkers, beyond PD-L1, to optimize patient selection and novel strategies to improve clinical outcomes.Keywords: immunotherapy, anti-PD-1/PD-L1 antibodies, non-small cell lung cancer

Cycling ergometer protocols are commonly integrated with a virtual reality environment (VRE), especially because of its static position that also allows multiple exercise experiments. Concerning VRE scenarios, visually delayed situations like the ones produced at excessive low update rates can also affect the sense of presence and physiological responses. However, the main interface between the subject and a cycling VRE is the power applied over the crank, and there are only a few experiments to evaluate the effect of delayed situations on this particular interface. Thus, this work aims to investigate the effects of the power update rate (PUR) over the subject's performance on an avatar-based simulator during a drafting task. A custom cycling VRE was built, and 21 male recreational cyclists (175.9 ± 7.5 cm; 76.5 ± 13.9 kg) were tested at six different PUR levels from 100 to 3000 ms. As a result, PUR affects performance scores (virtual distance, efficiency, and heart rate, p < 0.01) at the given VRE conditions. The case-by-case analysis of the groups reveals that higher update rates always lead to a statistical equivalent or superior performance. Nevertheless, no parameter shows any group difference between 500 ms and lower PUR. These results suggest that virtual cycling protocols should consider PUR and other delay-related mechanisms as possible intervening factors over physiological responses and performance scores. [ABSTRACT FROM AUTHOR]

Presents information on a study that described an experimental procedure for investigating the azimuthal anchoring of nematic liquid crystals by using a transmitted light method. Comparison between exact numerical results and first order results; Experimental procedure for separating bulk and surface contributions.

Objectives: One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. Material and Methods: We studied the variation of extracellular parameters -- such as medium volume, buffer system, nutrient concentrations and temperature on human colon carcinoma cells (CaCo-2) "in vitro culture" -- pursuing the goal of understanding in deeper details cellular processes such as growth, metabolic activity, survival and pH0. Results: Results showed that CaCo-2 cells growth and mortality increase after two days in culture when cells were suspended in 3.5 ml volume to respect of 10 ml volume. Different temperature values influenced CaCo-2 cells growth and metabolic activity showing a direct relationship with the volume of the medium. Conclusions: Our results describe as CaCo-2 cell growth, metabolic activity, mortality and extracellular pH were influenced by extracellular parameters, enabling us to develop and validate a numerical model to be use to predict cells engraftment and proliferation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiac resynchronization therapy (CRT) can be considered as an established therapy for patients with moderate or severe heart failure (HF), depressed systolic function and a wide QRS complex. Biventricular stimulation through the CRT is applied at patients with an intra and/or inter-ventricular conduction delay. The goal of this technique is to resynchronize contraction between and within ventricles. A numerical model of the cardiovascular system, together with the numerical model of the biventricular pacemaker (BPM), can be an useful tool to study the better synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay. Subjects and Methods: Within a group of patients which were representative of the most common disease etiologies of heart failure, seven patients, affected by dilated cardiomyopathy undergoing CRT with BPM, were studied and simulated using the numerical model of the cardiovascular system CARDIOSIM . The patients were submitted to echocardiographic evaluation (with pulsate Doppler and tissue Doppler imaging) and electrocardiography evaluation in order to evaluate intra-ventricular and/or inter-ventricular dyssynchrony. These evaluations were made three times: the first one before BPM implantation, the second and the third one respectively within seven days and six months after BPM implantation. Also haemodynamic parameters were measured. Using the software simulator, the pathological conditions before CRT, within seven days and within six months since CRT were reproduced for each patients in order to evaluate the following haemodynamic parameters: the end-systolic and end-diastolic left ventricular volume, the systolic pulmonary arterial pressure, the systolic, diastolic and mean aortic blood pressure and the ejection fraction. Also the trend of the left ventricular elastance was studied for each patient in order to evaluate the benefits produced by the CRT. Results: The results obtained by means the numerical simulator were in good agreement with clinical data measured on the patients. For each patient also the evolution of the left ventricular elastance was in accordance with the literature data. Conclusion: The cardiovascular numerical model seems to be a useful tool to study the synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay and to reproduce the condition of a patient. [ABSTRACT FROM AUTHOR]

In this paper, we present a new global error bound for the dual formulation of the support vector machine (SVM) whose penalty terms are measured by 2-norm (L2-SVM). An further formulation in which an additional term is added to the objective function is also considered (SCL2-SVM). A global error bound for the dual of the latter problem is derived. This error bound is used to identify those constraints of primal SCL2-SVM that will be active at the solution. The correct identification of active constraints is important to find the support vectors and to build the working set of most iterative algorithms for SVM. Computational results are presented showing that the proposed method is able to quickly identify a large percentage of constraints that are active at the optimal solution. [ABSTRACT FROM AUTHOR]

The article cites a study determining coronary flow waveforms through computer simulation. An open-chest pig was used as the model to monitor the phasic blood flow and the data were gathered before, during, and after the occlusion of caval. In the examination, the coronary flow-aortic pressure loops were reported to have prevailed an in vivo during occlusion and that waveforms are visible. The results of the study were concluded to show the capability of lumped parameter model to produce the alterations in the onset of caval occlusion.

Objectives: This work is another step in the development of the circulatory model CARDIOSIM and of its model library. Continuous flow assistance is often used to support the right ventricular failure. Computer simulation is one of the methods to study the effect of this assistance on the failing ventricle. The purpose of this study was to evaluate the effect of this support on some hemodynamic variables, when different right ventricular end-systolic elastance and pump speed values were applied.Methods: The rotary blood pump model was included into the software package CARDIOSIM, which reproduces the cardiovascular system. Lumped parameters models were used to reproduce the circulatory phenomena. Variable elastance models reproduced the Starling's law of the heart for both ventricles. In the study right ventricular end-systolic elastance (EmaxRIGHT) and the rotational speed of the pump took three different values. All the other parameters of the model were constants.Results: The rotational speed of the pump had a significant influence on right ventricular end-diastolic and end-systolic volumes, right atrial pressure (Pra), right ventricular (Qro) and pump flows. The effects on pulmonary arterial pressure (Pap) were more evident when the right ventricular end-systolic elastance was low. When the speed of the device increased the mean value of Pra decreased for each value of EmaxRIGHT. The total flow (Qro+pump flow) increased when the speed of the pump increased.Conclusions: Our simulation (in good agreement with the results presented in literature) showed that Hemopump produces a rise in total flow, a drop in blood flow pumped out by the right ventricle and a drop in right atrial pressure. [ABSTRACT FROM AUTHOR]

Objectives: Aim of this work is to study the impact of left ventricular rotary blood pump assistance, on energetic variables, when mechanical ventilation (MV) of the lungs is applied.Methods: Computer simulation was used to perform this study. Lumped parameter models reproduce the circulatory system. Variable elastance models reproduce the Starling's law of the heart for each ventricle. After the reproduction of ischemic heart disease left ventricular assistance was applied using a model of rotary blood pump. The pump speed was changed in steps and was assumed to be constant during each step. The influence of mechanical ventilation was introduced by different values of positive mean thoracic pressure.Results: The increase of the rotational speed has a significant influence on some ventricular energetic variables. In fact it decreased left ventricular external work, left and right ventricular pressure-volume area and the left ventricular efficiency. Finally, it increased the right ventricular efficiency but had no influence on the right ventricular external work. The increase of thoracic pressure from -2 to +5 mmHg caused a significant decrease of external work, pressure-volume area (right ventricular pressure-volume area dropped up to 50%) and an increase of right ventricular efficiency (by 40%) while left ventricular efficiency remained almost stable.Conclusions: Numerical simulation is a very suitable tool to predict changes of not easily measurable parameters such as energetic ventricular variables when mechanical assistance of heart and/or lungs is applied independently or simultaneously. [ABSTRACT FROM AUTHOR]

Carbon dioxide is generally recognized as an important cue used by haematophagous insects to locate a food source. When the mammalian hosts of these insects breathe, they normally emanate considerable amounts of CO2 at discrete intervals, i.e. with each exhalation. In this work, we analysed the effect of temporally pulsing CO2 on the host-seeking behaviour of Triatoma infestans. We investigated the ability of T. infestans to follow continuous and intermittent air pulses of 0.25, 0.5 and 1 Hz that included different concentrations of CO2. We found that insects were attracted to pulsed airstreams of 0.25 and 0.5 Hz transporting 400 ppm of CO2 above the ambient levels and to continuous streams added with the same amount of CO2. On the other hand, insects walked away from streams pulsed at rates of 1 Hz regardless of the amount of CO2 they bear. The walking trajectories displayed by bugs to attractive CO2-pulsed streams were as rectilinear and accurate as those to CO2-continuous streams. Our results are discussed in the frame of the interaction between olfactory and mechanoreceptive inputs as affecting the behavioural response of bugs. [ABSTRACT FROM AUTHOR]

Objectives: The analysis of energetic ventricular variable changes during artificial ventilation, obtained by numerical simulation was done. Twenty-one sets of hemodynamic parameters for eight cardiosurgical patients were used to estimate left and right stroke work. The data were collected for three methods of ventilation: conventional, lung-protective (with minute ventilation diminished by half) and high frequency ventilation (with frequency 5, 10, or 15 Hz).Methods: The computer simulator (CARDIOSIM) of the cardiovascular system, was used as a tool to calculate values of energetic ventricular variables for conditions that corresponded to these during in vivo measurements. Different methods of ventilation caused differences of intrathoracic pressure, haemodynamic and finally energetic ventricular variables. The trends of these variable changes were the same in in vivo and simulation studies, in the whole range of intrathoracic pressure changes (Pt = 1.5-3.5 mmHg).Results: As values of main hemodynamic variables like cardiac output or arterial, systemic and pulmonary pressures were very close in both studies. Cardiac index and left ventricular stroke work also differed less than 10% for all examined patients and computer simulation. In a case of right ventricular stroke work the difference between in vivo data and simulation was a bit greater than 10% for two of eight patients under study.Conclusions: Our comparative analysis proved that numerical simulation is a very useful tool to predict changes of main hemodynamic and energy-related ventricular variables caused by different levels of positive Pt. It means that it can help an anesthesiologist to choose an appropriate method of artificial ventilation for cardiosurgical patients. [ABSTRACT FROM AUTHOR]

We consider the problem of minimizing an SC¹ function subject to inequality constraints. We propose a local algorithm whose distinguishing features are that: (a) a fast convergence rate is achieved under reasonable assumptions that do not include strict complementarity at the solution; (b) the solution of only linear systems is required at each iteration; (c) all the points generated are feasible. After analyzing a basic Newton algorithm, we propose some variants aimed at reducing the computational costs and, in particular, we consider a quasi-Newton version of the algorithm. [ABSTRACT FROM AUTHOR]

The aim was to assess the influence of a biventricular assist device (BVAD) on ventricular energetics parameters (external work, oxygen consumption, cardiac mechanical efficiency) for both ventricles, when mechanical ventilation was applied. The experiments were performed using a computer simulator of cardiovascular system (CARDIOSIM[sup ©]) after modelling a pathological state of the left ventricle (E[sub VLEFT] = 0.9 mmHg cm[sup -3]) and increasing pulmonary resistance (Rap = 0.3 mmHg cm[sup -3] s). The effect of mechanical ventilation was mean intrathoracic pressure changes from 0 to +5 mmHg. This simulation showed that application of BVAD for both ventricles reduces external work and that this effect is stressed by positive intrathoracic pressure, reduces cardiac mechanical efficiency that is quite insensitive to intrathoracic pressure and increases oxygen consumption, which is reduced by positive intrathoracic pressure. The increase of potential energy at the onset of BVAD evidences a rightwards shift of ventricular work cycle (unloading of the ventricles). In general, positive intrathoracic pressure during BVAD assistance adversely affects ventricular energetics. [ABSTRACT FROM AUTHOR]

Computer simulation of a cardiovascular system enabled us to predict the effects of simultaneous application of mechanical ventilation (MV) and intraaortic ballon pumping (IABP) on ventricular energetics. External work (EW), pressure-volume area (PVA), potential energy (PE) and cardiac mechanical efficiency (CME) were calculated. Nummerical simulation showed that changes of positive intrathoracic pressure have a considerable effect on left and right ventricular EW, PE, PVA and CME, whether IABP is used or not. The right ventricular energetics was much less influenced by systemic resistance (Ras) changes than the left ventricular one. Simultaneous application of IABP and MV showed a remarkable effect on left ventricular EW. The net result was reversed sensitivity to pulmonary resistance (Rap) and reduced sensitivity to Ras. PVA was generally reduced, while CME is increased by simultaneous presence of IABP and MV. The sensitivity of CME to Rap and Ras variation was diminished in this situation. [ABSTRACT FROM AUTHOR]