Cyclosporine A micellar nasal spray characterization and antiviral action against SARS-CoV-2.

The upper airways represent the point of entrance from where Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection spreads to the lungs. In the present work, α-tocopheryl-polyethylene-glycol succinate (TPGS) micelles loaded with cyclosporine A (CSA) were developed for nasal administration to prevent or treat the viral infection in the very first phases. The behavior of the micelles in presence of simulated nasal mucus was investigated in terms of stability and mucopenetration rate, evidencing long-term stability and fast diffusion across the glycoproteins matrix. Moreover, the spray characteristics of the micellar formulation and deposition profile in a silicon nasal model were studied using three nasal spray devices. Results allowed to identify the nasal spray pump (BiVax, Aptar) able to provide the wider and uniform deposition of the nasal cavity. The cyclosporine A micelles antiviral activity against SARS-CoV-2 was tested on the Omicron BA.1 variant using Vero E6 cells with protocols simulating treatment before, during and after the infection of the upper airways. Complete viral inactivation was observed for the cyclosporine-loaded micelles while a very low activity was evidenced for the non-formulated drug, suggesting a synergistic activity of the drug and the formulation. In conclusion, this work showed that the developed cyclosporine A-loaded micellar formulations have the potential to be clinically effective against a wide spectrum of coronavirus variants.

Health effects of 100% fruit and vegetable juices: evidence from human subject intervention studies.

The health effects of 100% fruit and vegetable juices (FVJ) represent a controversial topic. FVJ contain notable amounts of free sugars, but also vitamins, minerals, and secondary compounds with proven biological activities like (poly)phenols and carotenoids. The review aimed to shed light on the potential impact of 100% FVJ on human subject health, comprehensively assessing the role each type of juice may have in specific health outcomes for a particular target population, as reported in dietary interventions. The effects of a wide range of FVJ (orange, grapefruit, mandarin, lemon, apple, white, red, and Concord grapes, pomegranate, cranberry, chokeberry, blueberry, other minor berries, sweet and tart cherry, plum, tomato, carrot, beetroot, and watermelon, among others) were evaluated on a series of outcomes (anthropometric parameters, body composition, blood pressure and vascular function, lipid profile, glucose homeostasis, biomarkers of inflammation and oxidative stress, cognitive function, exercise performance, gut microbiota composition and bacterial infections), providing a thorough picture of the contribution of each FVJ to a health outcome. Some juices demonstrated their ability to exert potential preventive effects on some outcomes while others on other health outcomes, emphasising how the differential composition in bioactive compounds defines juice effects. Research gaps and future prospects were discussed. Although 100% FVJ appear to have beneficial effects on some cardiometabolic health outcomes, cognition and exercise performance, or neutral effects on anthropometric parameters and body composition, further efforts are needed to better understand the impact of 100% FVJ on human subject health.

One-Lung Ventilation and Postoperative Pulmonary Complications After Major Lung Resection Surgery. A Multicenter Randomized Controlled Trial.

OBJECTIVES: The effect of one-lung ventilation (OLV) strategy based on low tidal volume (TV), application of positive end-expiratory pressure (PEEP), and alveolar recruitment maneuvers (ARM) to reduce postoperative acute respiratory distress syndrome (ARDS) and pulmonary complications (PPCs) compared with higher TV without PEEP and ARM strategy in adult patients undergoing lobectomy or pneumonectomy has not been well established. DESIGN: Multicenter, randomized, single-blind, controlled trial. SETTING: Sixteen Italian hospitals. PARTICIPANTS: A total of 880 patients undergoing elective major lung resection. INTERVENTIONS: Patients were randomized to receive lower tidal volume (LTV group: 4 mL/kg predicted body weight, PEEP of 5 cmH2O, and ARMs) or higher tidal volume (HTL group: 6 mL/kg predicted body weight, no PEEP, and no ARMs). After OLV, until extubation, both groups were ventilated using a tidal volume of 8 mL/kg and a PEEP value of 5 cmH2O. The primary outcome was the incidence of in-hospital ARDS. Secondary outcomes were the in-hospital rate of PPCs, major cardiovascular events, unplanned intensive care unit (ICU) admission, in-hospital mortality, ICU length of stay, and in-hospital length of stay. MEASUREMENTS AND MAIN RESULTS: ARDS occurred in 3 of 438 patients (0.7%, 95% CI 0.1-2.0) and in 1 of 442 patients (0.2%, 95% CI 0-1.4) in the LTV and HTV group, respectively (Risk ratio: 3.03 95% CI 0.32-29, p = 0.372). Pulmonary complications occurred in 125 of 438 patients (28.5%, 95% CI 24.5-32.9) and in 136 of 442 patients (30.8%, 95% CI 26.6-35.2) in the LTV and HTV group, respectively (risk ratio: 0.93, 95% CI 0.76-1.14, p = 0.507). The incidence of major complications, in-hospital mortality, and unplanned ICU admission, ICU and in-hospital length of stay were comparable in both groups. CONCLUSIONS: In conclusion, among adult patients undergoing elective lung resection, an OLV with lower tidal volume, PEEP 5 cmH2O, and ARMs and a higher tidal volume strategy resulted in low ARDS incidence and comparable postoperative complications, in-hospital length of stay, and mortality.

Behavioural Responses of Male Aedes albopictus to Different Volatile Chemical Compounds.

The Asian tiger mosquito, Aedes albopictus, has become one of the most important invasive vectors for disease pathogens such as the viruses that cause chikungunya and dengue. Given the medical importance of this disease vector, a number of control programmes involving the use of the sterile insect technique (SIT) have been proposed. The identification of chemical compounds that attract males can be very useful for trapping purposes, especially for monitoring the makeup of the male population during control programmes, such as those involving the use of the SIT. Twenty-eight chemical compounds from different chemical classes were evaluated using a dual-port olfactometer assay. The compounds included known animal, fungal and plant host volatiles, and components of a putative Aedes aegypti pheromone. Many of the compounds were repellent for male mosquitoes, especially at the highest concentration. One compound, decanoic acid, acted as an attractant for males at an intermediate concentration. Decanoic acid did not elicit a significant response from female mosquitoes.

A novel computerized assessment of manual spatial exploration in unilateral spatial neglect.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

A respirable HPV-L2 dry-powder vaccine with GLA as amphiphilic lubricant and immune-adjuvant.

Vaccines not requiring cold-chain storage/distribution and suitable for needle-free delivery are urgently needed. Pulmonary administration is one of the most promising non-parenteral routes for vaccine delivery. Through a multi-component excipient and spray-drying approach, we engineered highly respirable dry-powder vaccine particles containing a three-fold repeated peptide epitope derived from human papillomavirus (HPV16) minor capsid protein L2 displayed on Pyrococcus furious thioredoxin as antigen. A key feature of our engineering approach was the use of the amphiphilic endotoxin derivative glucopyranosyl lipid A (GLA) as both a coating agent enhancing particle de-aggregation and respirability as well as a built-in immune-adjuvant. Following an extensive characterization of the in vitro aerodynamic performance, lung deposition was verified in vivo by intratracheal administration in mice of a vaccine powder containing a fluorescently labeled derivative of the antigen. This was followed by a short-term immunization study that highlighted the ability of the GLA-adjuvanted vaccine powder to induce an anti-L2 systemic immune response comparable to (or even better than) that of the subcutaneously administered liquid-form vaccine. Despite the very short-term immunization conditions employed for this preliminary vaccination experiment, the intratracheally administered dry-powder, but not the subcutaneously injected liquid-state, vaccine induced consistent HPV neutralizing responses. Overall, the present data provide proof-of-concept validation of a new formulation design to produce a dry-powder vaccine that may be easily transferred to other antigens.

Resistant Tuberculosis: the Latest Advancements of Second-line Antibiotic Inhalation Products.

Drug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isoniazid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeruginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB.

A phase II trial of the FGFR inhibitor pemigatinib in patients with metastatic esophageal-gastric junction/gastric cancer trastuzumab resistant: the FiGhTeR trial.

BACKGROUND: Prognosis of patients affected by metastatic esophageal-gastric junction (EGJ) or gastric cancer (GC) remains dismal. Trastuzumab, an anti-HER2 monoclonal antibody, is the only targeted agent approved for the first-line treatment of patients with HER2-overexpressing advanced EGJ or GC in combination with chemotherapy. However, patients invariably become resistant during this treatment. We recently identified the overexpression of fibroblast growth factor (FGF) receptor 3 (FGFR3) as a molecular mechanism responsible for trastuzumab resistance in GC models, providing the rationale for the inhibition of this receptor as a potential second-line strategy in this disease. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. METHODS: The FiGhTeR trial is a phase II, single-arm, open-label study to assess safety and activity of the FGFR inhibitor pemigatinib as second-line treatment strategy in metastatic EGJ/GC patients progressing under trastuzumab-containing therapies. The primary endpoint is the 12-week progression-free survival rate. Plasma and tumor tissue samples will be collected for translational research analyses at baseline, during treatment, and at progression on pemigatinib. DISCUSSION: Co-alterations in genes coding for different tyrosine-kinase receptors are emerging as relevant mechanisms of acquired resistance to anti-HER2 therapeutic strategies in GC. In particular, our group has recently identified that in GC models the overexpression of FGFR3 sustains the acquired resistance to trastuzumab. This trial aims to assess the safety, tolerability and activity of the FGFR inhibitor pemigatinib as a second-line treatment in metastatic EGJ/GC patients refractory to first-line trastuzumab-containing therapies. Furthermore, this study offers the opportunity to prospectively study mechanisms and pathways involved in trastuzumab resistance. PROTOCOL NUMBER: CRC2017_02. EUDRACT NUMBER: 2017-004522-14.

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

BACKGROUND: Up-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good performance status. liposomal irinotecan (Nal-IRI) is a novel nanoliposome formulation of irinotecan that accumulates in tumor-associated macrophages improving the therapeutic index of irinotecan and has been approved for the treatment of patients with metastatic pancreatic cancer after progression under gemcitabine-based therapy. Thus, it remains of the outmost urgency to investigate introduction of the most novel agents, such as nal-IRI, in perioperative approaches aimed at increasing the long-term effectiveness of surgery. METHODS: The nITRO trial is a phase II, single-arm, open-label study to assess the safety and the activity of nal-IRI with fluorouracil/leucovorin (5-FU/LV) and oxaliplatin in the perioperative treatment of patients with resectable pancreatic cancer. The primary tumor must be resectable with no involvement of the major arteries and no involvement or <180° interface between tumor and vessel wall of the major veins. A total of 72 patients will be enrolled to receive a perioperative treatment of three cycles before and three cycles after surgical resection with nal-IRI 50 mg/m2, oxaliplatin 60 mg/m2, leucovorin 200 mg/m2, and 5-fluorouracil 2400 mg/m2, days 1 and 15 of a 28-day cycle. The primary objective is to improve from 40% to 55% the proportion of patients achieving R0 resection after preoperative treatment. DISCUSSION: The nITRO trial will contribute to strengthen the clinical evidence supporting perioperative strategies in resectable pancreatic cancer patients. Moreover, this study represents a unique opportunity for translational analyses aimed to identify novel immune-related prognostic and predictive factors in this setting. TRIAL REGISTRATION: Clinicaltrial.gov: NCT03528785. Trial registration data: 1 January 2018Protocol number: CRC 2017_01EudraCT Number: 2017-000345-46.

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections.

Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rifampicin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 µm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance.

Exploring prism exposure after hemispheric damage: Reduced aftereffects following left-sided lesions.

Prism adaptation is a well-known method used to investigate brain plasticity, and a promising technique for the rehabilitation of unilateral spatial neglect (USN). Only little evidence about the mechanisms of prism adaptation (PA) in patients with left-brain damage is on record, and about putative differences of PA, and the aftereffects (AEs), between patients with left and right brain damage. In the present study, PA and the AEs were assessed in 30 brain-damaged patients, 20 with right-sided lesions (10 with and 10 without USN), and 10 with left-sided lesions without USN, as well as in a control group of 24 age-matched participants. All patients underwent adaptation to lenses shifting the field of vision towards the side of the lesion, followed by two measures for detecting AEs: the proprioceptive (P) and the visuo-proprioceptive (VP) straight-ahead tasks. To investigate the temporal course of AEs in the different groups, the two measures were recorded immediately and 10 min after PA. Before PA, and at the end of the 10-min delayed evaluation, two tasks to assess USN (target cancellation and drawing) were also administered. All patients adapted to prisms. However, left-brain-damaged (LBD) patients presented with reduced AEs, as compared with right-brain-damaged (RBD) patients with USN. Moreover, while both controls and LBD patients adapting to left-shifting prisms had reduced VP AEs in the delayed condition, AEs were not different from zero (i.e., no AEs) in LBD patients. Finally, in the delayed condition USN patients showed an improvement in the drawing, but not in the cancellation, tasks. These results suggest that adaptation to leftward shifting lenses is associated with larger decay of VP AEs, and a role of the left hemisphere in maintaining these AEs after PA. These findings can be of relevance for the clinical application of this technique in neurological populations.

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy.

Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ10 nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02µm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ10.

Accessorized DPI: a Shortcut towards Flexibility and Patient Adaptability in Dry Powder Inhalation.

PURPOSE: In this work, a novel powder dispersion add-on device, the AOS (Axial Oscillating Sphere), was studied in conjunction with commercially available DPI devices to improve the powder dispersion. METHODS: An ordered mixture of formoterol fumarate and lactose was selected. We studied in two laboratories located at different altitudes the dispensing and dispersion of the drug at different flow rates, paying particular attention to a number of metrics of Fine Particle Dose (FPD). RESULTS: Two novel findings emerged from the data collected. First, the aerosol quality, measured as fine particle dose, can be increased by adding the accessory promoting the dispersion and de-aggregation of the formulation. The second finding was that, albeit the emitted dose was independent of altitude, the drug/lactose carrier DPI aerosolizing performance changed with the altitude of testing. In particular, fine particle dose depended on both altitude and device configuration. The RS01 inhaler without the AOS accessory used at higher altitude gave the lowest FPD values. By combining the AOS accessory with the DPI, however, the performance dependence on altitude/atmospheric pressure was essentially removed. CONCLUSIONS: Increasing inhaler performance can be achieved using an add-on accessory that enhances aerosol dispersion and minimizes flow rate dependency.

Combinations of colistin solutions and nebulisers for lung infection management in cystic fibrosis patients.

In this work different nebulisers were investigated in order to assess their efficiency in combination with colistimethate sodium (CMS) inhalation products. Four nebulisers, namely I-neb(®), Aeroneb(®) Go, eFlow(®)rapid and PARI LC(®) Sprint were studied in terms of delivered dose (DD), drug delivery rate (DDR) and respirable dose (RD) of CMS. The goal was to provide scientific data to physicians for prescribing the most appropriate nebuliser for the CMS specific user. All the apparatuses nebulised ColiFin 1MIU/3 ml solution (80 mg of CMS) with delivered doses between 31% and 41% of the loaded amount. Aeroneb Go showed the longest nebulisation time (more than 20 min). When ColiFin 2 MIU/4 ml was nebulised with eFlow rapid or PARI LC Sprint, the CMS respirable dose was 45.3mg and 39.2mg, in times of 5.6 and 10.8 min, respectively. I-neb, having a medication cup capacity limited to 0.4 ml, loaded with Promixin 0.4 MIU/0.4 ml (32 mg of CMS), provided in a time of 9 min a RD of 21.5mg, a value slightly higher than those obtained by nebulising ColiFin 1 MIU/3 ml with the other nebulisers (range 15.9-17.6 mg). The results illustrate that the clinical outcome depends on the comparative analysis of nebulisation efficiency (respirable dose) and convenience (time), not disregarding the ratios between the amount loaded, delivered and deposited at lung level.

Hyperschematia after right brain damage: a meaningful entity?

In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term "hyperschematia" for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with "hyperschematia" includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left "hyperschematia" involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal "hyperschematia"). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, "hypeschematia" is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings.

Extubación postoperatoria inmediata (ultra fast-track) en cirugía coronaria sin circulación extracorpórea / Immediate postoperative extubation (ultra fast-track) after coronary surgery without cardiopulmonary bypass

Antecedentes: La ventilación en el postoperatorio es una práctica rutinaria en los pacientes sometidos a cirugía de revascularización miocárdica. En los últimos años, junto con la incorporación de la cirugía de revascularización miocárdica (CRM) sin circulación extracorpórea (sin CEC), hemos adoptado como objetivo la extubación en el quirófano, es decir, al finalizar la cirugía. Objetivos: Extubación inmediata en quirófano (ultra fast-track (UFT)) utilizando anestesia general; secundariamente, analizar la curva de aprendizaje durante el período de estudio. Lugar de aplicación: Institución privada. Diseño: Estudio retrospectivo, casuístico, observacional. Población: 209 pacientes sometidos a CRM sin CEC durante el período que va de julio de 2002 a abril de 2003. Se incluyeron todos los pacientes en forma consecutiva, sin criterios de exclusión. Método: Anestesia general balanceada intravenosa e inhalatoria. Se evaluaron las características preoperatorias, las condiciones necesarias para la extubación, el número de pacientes extubados y el de no extubados, y sus causas. Los pacientes fueron divididos en dos grupos: G02 = 2002 (110 pacientes) y G03 = 2003 (99 pacientes). Resultados: De las condiciones preoperatorias, hubo diferencia estadísticamente significativa entre G02 y G03, con mayor severidad para este último en tabaquismo (p = 0.007), clase funcional III-IV (p = 0.009) y función ventricular moderada-severa (p = 0.021). Hubo tendencia, pero sin significación estadística, también hacia G03 en cirugía no electiva, balón de contrapulsación intra aórtico, diabetes y reoperación. Se extubó el 81 por ciento de los pacientes en el quirófano, un 71 por ciento del período '02 y 92 por ciento del periodo '03. Los no extubados obedecieron a: falta de conciencia 13 (11/2), inestabilidad hemodinámica 13 (7/6), cambios eléctricos 3 (3/0), sangrado 3 (3/0), respiratorias 3 (3/0) y conversión a CEC 5 (5/0). Las complicaciones fueron: respiratorias: 4.8 por ciento, distress: 0.9 por ciento, IAM 2.9 por ciento y mortalidad 3.8 por ciento. La estadía en UTI fue de 1 día y la estadía total 5 días. Conclusión: Es posible realizar la extubación en quirófano para cirugía de revascularización miocárdica sin circulación extracorpórea utilizando anestesia general balanceada, ajustándola a la técnica de UFT. También la curva de aprendizaje ha influido favorablemente en los resultados.