A Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions.

Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrPC) into a pathogenic form (PrPSc). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

Lung and blood perioperative metalloproteinases in patients undergoing oncologic lung surgery: Prognostic implications.

BACKGROUND: Metalloproteinases (MMPs) have been reported to be related to oncologic outcomes. The main goal of the study was to study the relationship between these proteins and the long-term prognosis of patients undergoing oncologic lung resection surgery. METHODS: This was a substudy of the phase IV randomized control trial (NCT02168751). We analyzed MMP-2, -3, -7, and -9 in blood samples and bronchoalveolar lavage (LBA) and the relationship between MMPs and long postoperative outcomes (survival and disease-free time of oncologic recurrence). RESULTS: Survival was longer in patients who had lower MMP-2 levels than those with higher MMP-2 in blood samples taken 6 h after surgery (6.8 vs. 5.22 years; p = 0.012) and MMP-3 (6.82 vs. 5.35 years; p = 0.03). In contrast, survival was longer when MMP-3 levels were higher in LBA from oncologic lung patients than those with lower MMP-3 (7.96 vs. 6.02 years; p = 0.005). Recurrence-free time was longer in patients who had lower MMP-3 levels in blood samples versus higher (5.97 vs. 4.23 years; p = 0.034) as well as lower MMP-7 (5.96 vs. 4.5 years; p = 0.041) or lower MMP-9 in LBA samples (6.21 vs. 4.18 years; p = 0.012). CONCLUSION: MMPs were monitored during the perioperative period of oncologic lung resection surgery. These biomarkers were associated with mortality and recurrence-free time. The role of the different MMPs analyzed during the study do not have the same prognostic implications after this kind of surgery.

Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation.

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process.

Mortality Risk Prediction in Abdominal Septic Shock Treated with Polymyxin-B Hemoperfusion: A Retrospective Cohort Study.

Endotoxin, a component of the cell membrane of gram-negative bacteria, is a trigger for dysregulated inflammatory response in sepsis. Extracorporeal purification of endotoxin, through adsorption with polymyxin B, has been studied as a therapeutic option for sepsis. Previous studies suggest that it could be effective in patients with high endotoxin levels or patients with septic shock of moderate severity. Here, we perform a retrospective, single-centre cohort study of 93 patients suffering from abdominal septic shock treated with polymyxin-B hemoperfusion (PMX-HP) between 2015 and 2020. We compared deceased and surviving patients one month after the intervention using X2 and Mann-Whitney U tests. We assessed the data before and after PMX-HP with a Wilcoxon single-rank test and a multivariate logistic regression analysis. There was a significant reduction of SOFA score in the survivors. The expected mortality using APACHE-II was 59.62%, whereas in our sample, the rate was 40.9%. We found significant differences between expected mortality and real mortality only for the group of patients with an SOFA score between 8 and 13. In conclusion, in patients with abdominal septic shock, the addition of PMX-HP to the standard therapy resulted in lower mortality than expected in the subgroup of patients with intermediate severity of illness.

Feasibility of using KardiaMobile-L6 for QT interval monitoring during the early phase of the COVID-19 pandemic in critical care patients.

The electrocardiogram (ECG) represents an essential tool to determine cardiac electrical abnormalities in COVID-19 patients, the effects of anti-SARS-CoV-2 drugs, and potential drug interactions. Smartphone-based heart monitors have increased the spectrum of ECG monitoring however, we are not aware of its reliability in critically ill COVID-19 patients. We aim to evaluate the feasibility and reliability of nurse-performed smartphone electrocardiography for QT interval monitoring in critically ill COVID-19 patients using KardiaMobile-6L compared with the standard 12-lead ECG. An observational comparative study was conducted comparing consecutive KardiaMobile-6L and 12-lead ECG recordings obtained from 20 patients admitted to the intensive care unit with SARS-CoV-2 infection and on invasive mechanical ventilation. The heart rate-corrected QT (QTc) intervals measured by KardiaMobile-6L and 12-lead ECG were compared. In 60 percent of the recordings, QTc intervals measured by KardiaMobile-6L matched those by 12-lead ECG. The QTc intervals measured by KardiaMobile-6 and 12-lead ECG were 428 ± 45 ms and 425 ± 35 ms (p = 0.82), respectively. The former demonstrated good agreement (bias = 2.9 ms; standard deviation of bias = 29.6 ms) with the latter, using the Bland-Altman method of measurement agreement. In all but one recording, KardiaMobile-6L demonstrated QTc prolongation. QTc interval monitoring with KardiaMobile-6L in critically ill COVID-19 patients was feasible and demonstrated reliability comparable to the standard 12-lead ECG.

Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. METHODS: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan-Meier and Cox regression analysis. RESULTS: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis (p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11-1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99-1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. CONCLUSION: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

Influence of postoperative complications on long-term outcome after oncologic lung resection surgery. Substudy of a randomized control trial.

Lung resection surgery (LRS) causes an intense local and systemic inflammatory response. There is a relationship between inflammation and postoperative complications (POCs). Also, it has been proposed that the inflammation and complications related with the surgery may promote the recurrence of cancer and therefore deterioration of survival. We investigated the association between inflammatory biomarkers, severity of POCs and long-term outcome in patients who were discharged after LRS. This is a prospective substudy of a randomized control trial. We established three groups based in the presence of POCs evaluated by Clavien-Dindo (C-D) classification: Patients with no postoperative complications (No-POCs group) (C-D = 0), patients who developed light POCs (L-POCs group) (C-D = I-II), and major POCs (M-POCs group) (C-D = III, IV, or V). Kaplan-Meier curves and Cox regression model were created to compare survival and oncologic recurrence in those groups. Patients who developed POCs (light or major) had an increase in some inflammatory biomarkers (TNF-α, IL-6, IL-7, IL-8) compared with No-POCs group. This pro-inflammatory status plays a fundamental role in the appearance of POCs and therefore in a shorter life expectancy. Individuals in the M-POCs group had a higher risk of death (HR = 3.59, 95% CI 1.69 to 7.63) compared to individuals in the No-POCs group (p = 0.001). Patients of L-POCs group showed better survival than M-POCs group (HR = 2.16, 95% CI 1.00 to 4.65, p = 0.049). Besides, M-POCs patients had higher risk of recurrence in the first 2 years, when compared with L-POCs (p = 0,008) or with No-POCs (p = 0.002). In patients who are discharged after undergoing oncologic LRS, there is an association between POCs occurrence and long term outcome. Oncologist should pay special attention in patients who develop POCs after LRS.

Intraoperative Troponin Elevation in Liver Transplantation Is Independently Associated With Mortality: A Prospective Observational Study.

Intraoperative factors implicated in postoperative mortality after liver transplantation (LT) are poorly understood. Because LT is a particularly demanding procedure, we hypothesized that intraoperative myocardial injury may be frequent and independently associated with early postoperative outcomes. We aimed to determine the association between intraoperative high-sensitivity troponin (hsTn) elevation during LT and 30-day postoperative mortality. A total of 203 adult patients undergoing LT were prospectively included in the cohort and followed during 1 year. Advanced hemodynamic parameters and serial high-sensitivity troponin T (hsTnT) measurements were assessed at 6 intraoperative time points. The optimal hsTnT cutoff level for intraoperative troponin elevation (ITE) was identified. Patients were classified into 2 groups according to the presence of ITE. Independent impact of ITE on survival was assessed through survival curves and multivariate Cox regression analysis. Intraoperative cardiac function was compared between groups. Troponin levels increased early during surgery in the ITE group. Troponin values at abdominal closure were associated with 30-day mortality (area under the receiver operating caracteristic curve, [AUROC], 0.73; P = 0.005). Patients with ITE showing values of hsTnT ≥61 ng/L at abdominal closure presented higher 30-day mortality (29.6% versus 3.4%; P < 0.001). ITE was independently associated with 30-day mortality (hazard ratio, 3.8; 95% confidence interval, 1.1-13.8; P = 0.04) and with worse overall intraoperative cardiac function. The hsTnT upper reference limit showed no discriminant capacity during LT. Intraoperative myocardial injury identified by hsTn elevation is frequently observed during LT, and it is associated with myocardial dysfunction and short-term mortality. Determinations of hsTn may serve as a valuable intraoperative monitoring tool during LT.

Effect of intraoperative paravertebral or intravenous lidocaine versus control during lung resection surgery on postoperative complications: A randomized controlled trial.

BACKGROUND: Use of minimally invasive surgical techniques for lung resection surgery (LRS), such as video-assisted thoracoscopy (VATS), has increased in recent years. However, there is little information about the best anesthetic technique in this context. This surgical approach is associated with a lower intensity of postoperative pain, and its use has been proposed in programs for enhanced recovery after surgery (ERAS). This study compares the severity of postoperative complications in patients undergoing LRS who have received lidocaine intraoperatively either intravenously or via paravertebral administration versus saline. METHODS/DESIGN: We will conduct a single-center randomized controlled trial involving 153 patients undergoing LRS through a thoracoscopic approach. The patients will be randomly assigned to one of the following study groups: intravenous lidocaine with more paravertebral thoracic (PVT) saline, PVT lidocaine with more intravenous saline, or intravenous remifentanil with more PVT saline. The primary outcome will be the comparison of the postoperative course through Clavien-Dindo classification. Furthermore, we will compare the perioperative pulmonary and systemic inflammatory response by monitoring biomarkers in the bronchoalveolar lavage fluid and blood, as well as postoperative analgesic consumption between the three groups of patients. We will use an ANOVA to compare quantitative variables and a chi-squared test to compare qualitative variables. DISCUSSION: The development of less invasive surgical techniques means that anesthesiologists must adapt their perioperative management protocols and look for anesthetic techniques that provide good analgesic quality and allow rapid rehabilitation of the patient, as proposed in the ERAS protocols. The administration of a continuous infusion of intravenous lidocaine has proven to be useful and safe for the management of other types of surgery, as demonstrated in colorectal cancer. We want to know whether the continuous administration of lidocaine by a paravertebral route can be substituted with the intravenous administration of this local anesthetic in a safe and effective way while avoiding the risks inherent in the use of regional anesthetic techniques. In this way, this technique could be used in a safe and effective way in ERAS programs for pulmonary resection. TRIAL REGISTRATION: EudraCT, 2016-004271-52; ClinicalTrials.gov, NCT03905837 . Protocol number IGGFGG-2016 version 4.0, 27th April 2017.

Predictive value of plasma cytokines for acute kidney injury following lung resection surgery: prospective observational study / Valor preditivo das citocinas plasmáticas para lesão renal aguda após cirurgia de ressecção pulmonar: estudo observacional prospectivo

Abstract Background and objectives: Patients undergoing lung resection surgery are at risk of developing postoperative acute kidney injury. Determination of cytokine levels allows the detection of an early inflammatory response. We investigated any temporal relationship among perioperative inflammatory status and development of acute kidney injury after lung resection surgery. Furthermore, we evaluated the impact of acute kidney injury on outcome and analyzed the feasibility of cytokines to predict acute kidney injury. Methods: We prospectively analyzed 174 patients scheduled for elective lung resection surgery with intra-operative periods of one-lung ventilation periods. Fiberoptic broncho-alveolar lavage was performed in each lung before and after one-lung ventilation periods for cytokine analysis. As well, cytokine levels were measured from arterial blood samples at five time points. acute kidney injury was diagnosed within 48 h of surgery based on acute kidney injury criteria. We analyzed the association between acute kidney injury and cardiopulmonary complications, length of intensive care unit and hospital stays, intensive care unit re-admission, and short-term and long-term mortality. Results: The incidence of acute kidney injury in our study was 6.9% (12/174). Acute kidney injury patients showed higher plasma cytokine levels after surgery but differences in alveolar cytokines were not detected. Although no patient required renal replacement therapy, acute kidney injury patients had higher incidence of cardiopulmonary complications and increased overall mortality. Plasma interleukin-6 at 6 h was the most predictive cytokine of acute kidney injury (cut-off point at 4.89 pg.mL-1). Conclusions: Increased postoperative plasma cytokine levels are associated with acute kidney injury after lung resection surgery in our study, which worsens the prognosis. Plasma interleukin-6 may be used as an early indicator for patients at risk of developing acute kidney injury after lung resection surgery.

Resumo Justificativa e objetivos: Os pacientes submetidos à cirurgia de ressecção pulmonar apresentam risco de desenvolver lesão renal aguda pós-operatória. A determinação dos níveis de citocinas permite detectar uma resposta inflamatória precoce. Investigamos a relação temporal entre o estado inflamatório perioperatório e o desenvolvimento de lesão renal aguda após cirurgia de ressecção pulmonar. Além disso, avaliamos o impacto da lesão renal aguda no desfecho e analisamos a viabilidade das citocinas para prever este tipo de lesão. Métodos: No total, foram analisados prospectivamente 174 pacientes agendados para cirurgia eletiva de ressecção pulmonar com períodos intraoperatórios de ventilação monopulmonar. Lavado bronco-alveolar com fibra óptica foi realizado em cada pulmão antes e após os períodos de ventilação monopulmonar para análise das citocinas. Os níveis de citocina foram medidos a partir de amostras de sangue arterial em cinco momentos. A lesão renal aguda foi diagnosticada dentro de 48 horas após a cirurgia, com base nos critérios para sua verificação. Analisamos a associação entre lesão renal aguda e complicações cardiopulmonares, tempo de internação em unidade de terapia intensiva e de internação hospitalar, reinternação em unidade de terapia intensiva e mortalidade a curto e longo prazos. Resultados: A incidência de lesão renal aguda no estudo foi de 6,9% (12/174). Os pacientes com lesão renal aguda apresentaram níveis mais altos de citocinas plasmáticas após a cirurgia, mas não foram detectadas diferenças nas citocinas alveolares. Embora nenhum paciente tenha precisado de terapia renal substitutiva, os com lesão renal aguda apresentaram maior incidência de complicações cardiopulmonares e aumento da mortalidade geral. A interleucina-6 plasmática em seis horas foi a citocina mais preditiva de lesão renal aguda (ponto de corte em 4,89 pg.mL-1). Conclusões: O aumento dos níveis plasmáticos de citocinas no pós-operatório está associado à lesão renal aguda após cirurgia de ressecção pulmonar no estudo, o que piora o prognóstico. A interleucina-6 plasmática pode ser usada como um indicador precoce para pacientes com risco de desenvolver lesão renal aguda após cirurgia de ressecção pulmonar.

[Predictive value of plasma cytokines for acute kidney injury following lung resection surgery: prospective observational study]. / Valor preditivo das citocinas plasmáticas para lesão renal aguda após cirurgia de ressecção pulmonar: estudo observacional prospectivo.

BACKGROUND AND OBJECTIVES: Patients undergoing lung resection surgery are at risk of developing postoperative acute kidney injury. Determination of cytokine levels allows the detection of an early inflammatory response. We investigated any temporal relationship among perioperative inflammatory status and development of acute kidney injury after lung resection surgery. Furthermore, we evaluated the impact of acute kidney injury on outcome and analyzed the feasibility of cytokines to predict acute kidney injury. METHODS: We prospectively analyzed 174 patients scheduled for elective lung resection surgery with intra-operative periods of one-lung ventilation. Fiberoptic broncho-alveolar lavage was performed in each lung before and after one-lung ventilation periods for cytokine analysis. As well, cytokine levels were measured from arterial blood samples at five time points. Acute kidney injury was diagnosed within 48h of surgery based estabilished criteria for its diagnosis. We analyzed the association between acute kidney injury and cardiopulmonary complications, length of intensive care unit and hospital stays, intensive care unit re-admission, and short-term and long-term mortality. RESULTS: The incidence of acute kidney injury in our study was 6.9% (12/174). Acute kidney injury patients showed higher plasma cytokine levels after surgery, but differences in alveolar cytokines were not detected. Although no patient required renal replacement therapy, acute kidney injury patients had higher incidence of cardiopulmonary complications and increased overall mortality. Plasma interleukin-6 at 6h was the most predictive cytokine of acute kidney injury (cut-off point at 4.89pg.mL-1). CONCLUSIONS: Increased postoperative plasma cytokine levels are associated with acute kidney injury after lung resection surgery in our study, which worsens the prognosis. Plasma interleukin-6 may be used as an early indicator for patients at risk of developing acute kidney injury after lung resection surgery.

Usefulness of combining clinical and biochemical parameters for prediction of postoperative pulmonary complications after lung resection surgery.

Early detection of patients with a high risk of postoperative pulmonary complications (PPCs) could improve postoperative strategies. We investigated the role of monitoring systemic and lung inflammatory biomarkers during surgery and the early postoperative period to detect patients at high risk of PPCs after lung resection surgery (LRS). This is a substudy of a randomized control trial on the inflammatory effects of anaesthetic drugs during LRS. We classified patients into two groups, depending on whether or not they developed PPCs. We constructed three multivariate logistic regression models to analyse the power of the biomarkers to predict PPCs. Model 1 only included the usual clinical variables; Model 2 included lung and systemic inflammatory biomarkers; and Model 3 combined Models 1 and 2. Comparisons between mathematical models were based on the area under the receiver operating characteristic curve (AUROC) and tests of integrated discrimination improvement (IDI). Statistical significance was set at p < 0.05. PPCs were detected in 37 (21.3%) patients during admission. The AUROC for Models 1, 2, and 3 was 0.79 (95% CI 0.71-0.87), 0.80 (95% CI 0.72-0.88), and 0.93 (95% CI 0.88-0.97), respectively. Comparison of the AUROC between Models 1 and 2 did not reveal statistically significant values (p = 0.79). However, Model 3 was superior to Model 1 (p < 0.001). Model 3 had had an IDI of 0.29 (p < 0.001) and a net reclassification index of 0.28 (p = 0.007). A mathematical model combining inflammation biomarkers with clinical variables predicts PPCs after LRS better than a model that includes only clinical data. Clinical registration number Clinical Trial Registration NCT02168751; EudraCT 2011-002294-29.

Behavior of stroke volume variation in hemodynamic stable patients during thoracic surgery with one-lung ventilation periods / Comportamento da variação do volume sistólico em pacientes hemodinamicamente estáveis durante cirurgia torácica com períodos de ventilação monopulmonar

Abstract Introduction: In last few years, emphasis was placed in goal-directed therapy in order to optimize patient's hemodynamic status and improve their prognosis. Parameters based on the interaction between heart and lungs have been questioned in situations like low tidal volume and open chest surgery. The goal of the study was to analyze the changes that one-lung ventilation can produce over stroke volume variation and to assess the possible impact of airway pressures and lung compliance over stroke volume variation. Methods: Prospective observational study, 112 patients undergoing lung resection surgery with one-lung ventilation periods were included. Intravenous fluid therapy with crystalloids was set at 2 mL.g-1. Hypotension episodes were treated with vasoconstrictive drugs. Two-lung Ventilation was implemented with a TV of 8 mL.g-1 and one-lung ventilation was managed with a TV of 6 mL.g-1. Invasive blood pressure was monitored. We recorded the following cardiorespiratory values: heart rate, mean arterial pressure, cardiac index, stroke volume index, airway peak pressure, airway plateau pressure and static lung compliance at 3 different times during surgery: immediately after lung collapse, 30 min after initiating one-lung ventilation and after restoration of two-lung ventilation. Results: Stroke volume variation values were influenced by lung collapse (before lung collapse 14.6 (DS) vs. OLV 9.9% (DS), p < 0.0001); or after restoring two-lung ventilation (11.01 (DS), p < 0.0001). During two-lung Ventilation there was a significant correlation between airway pressures and stroke volume variation, however this correlation lacks during one-lung ventilation. Conclusion: The decrease of stroke volume variation values during one-lung ventilation with protective ventilatory strategies advices not to use the same threshold values to determine fluid responsiveness.

Resumo Introdução: Nos últimos anos, a importância da terapia alvo-dirigida foi enfatizada para aprimorar o estado hemodinâmico do paciente e melhorar seu prognóstico. Os parâmetros baseados na interação entre o coração e os pulmões foram questionados em situações como baixo volume corrente e cirurgia aberta do tórax. O objetivo do estudo foi analisar as alterações que a ventilação monopulmonar pode produzir na variação do volume sistólico e avaliar o possível impacto das pressões da via aérea e da complacência pulmonar sobre a variação do volume sistólico. Métodos: Estudo observacional prospectivo, no qual 112 pacientes submetidos à cirurgia de ressecção pulmonar com períodos de ventilação monopulmonar foram incluídos. A terapia de fluídos intravenosos com cristaloides foi ajustada a 2 mL.kg-1.h-1. Os episódios de hipotensão foram tratados com vasoconstritores. A ventilação dos dois pulmões (VDP) foi implantada com volume corrente de 8 mL.kg-1 e a ventilação monopulmonar foi controlada com volume corrente de 6 mL.kg-1. Foi monitorada a pressão arterial invasiva. Registramos os seguintes valores cardiorrespiratórios: frequência cardíaca, pressão arterial média, índice cardíaco, índice de volume sistólico, pressão de pico das vias aéreas, pressão de platô das vias aéreas e complacência pulmonar estática em três tempos durante a cirurgia: imediatamente após o colapso do pulmão, 30 minutos após o início da ventilação monopulmonar e após a restauração da ventilação dos dois pulmões. Resultados: Os valores de variação do volume sistólico foram influenciados pelo colapso pulmonar (antes do colapso pulmonar 14,6 [DS] vs. ventilação monopulmonar 9,9% [DS], p < 0,0001), ou após o restabelecimento da ventilação dos dois pulmões (11,01 [DS], p < 0,0001). Durante a ventilação dos dois pulmões houve uma correlação significativa entre as pressões das vias aéreas e a variação do volume sistólico, porém, essa correlação não existe durante a ventilação monopulmonar. Conclusão: A diminuição dos valores da variação do volume sistólico durante a ventilação monopulmonar com estratégias ventilatórias protetoras sugere não usar os mesmos valores de limiar para determinar a responsividade aos fluídos.

[Behaviour of stroke volume variation in hemodynamic stable patients during thoracic surgery with one-lung ventilation periods]. / Comportamento da variação do volume sistólico em pacientes hemodinamicamente estáveis durante cirurgia torácica com períodos de ventilação monopulmonar.

INTRODUCTION: In last few years, emphasis was placed in goal-directed therapy in order to optimize patient's hemodynamic status and improve their prognosis. Parameters based on the interaction between heart and lungs have been questioned in situations like low tidal volume and open chest surgery. The goal of the study was to analyze the changes that one-lung ventilation can produce over stroke volume variation and to assess the possible impact of airway pressures and lung compliance over stroke volume variation. METHODS: Prospective observational study, 112 patients undergoing lung resection surgery with one-lung ventilation periods were included. Intravenous fluid therapy with crystalloids was set at 2mL.kg-1.h-1. Hypotension episodes were treated with vasoconstrictive drugs. Two-lung ventilation was implemented with a TV of 8mL.kg-1 and one-lung ventilation was managed with a TV of 6mL.kg-1. Invasive blood pressure was monitored. We recorded the following cardiorespiratory values: heart rate, mean arterial pressure, cardiac index, stroke volume index, airway peak pressure, airway plateau pressure and static lung compliance at 3 different times during surgery: immediately after lung collapse, 30minutes after initiating one-lung ventilation and after restoration of two-lung ventilation. RESULTS: Stroke volume variation values were influenced by lung collapse (before lung collapse14.6 (DS) vs. OLV 9.9% (DS), p < 0.0001); or after restoring two-lung ventilation (11.01 (DS), p < 0.0001). During two-lung ventilation there was a significant correlation between airwaypressures and stroke volume variation, however this correlation lacks during one-lung ventilation. CONCLUSION: The decrease of stroke volume variation values during one-lung ventilation with protective ventilatory strategies advices not to use the same threshold values to determine fluid responsiveness.

Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial.

BACKGROUND: The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. METHODS: We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m2. Patients were randomly assigned (1:1:1:1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. FINDINGS: Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0·89 [95% CI 0·74-1·07; p=0·25]), OLA-CPAP (111 [47%] of 238, 0·91 [0·76-1·09; p=0·35]), or STD-CPAP groups (118 [48%] of 244, 0·95 [0·80-1·14; p=0·65]) when compared with patients in the STD-O2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. INTERPRETATION: In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation. FUNDING: Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness, and Grants Programme of the European Society of Anaesthesiology.

Variation in posture quality across musical instruments and its impact during performances.

OBJECTIVE: Bad posture increases the risk that a musician may suffer from musculoskeletal disorders. This study compared posture quality required by different instruments or families of instruments. METHODS: Using an ad-hoc postural observation instrument embracing 11 postural variables, four experts evaluated the postures of 100 students attending a Spanish higher conservatory of music. RESULTS: The agreement of the experts' evaluations was statistically confirmed by a Cohen's κ value between 0.855 and 1.000 and a Kendall value between 0.709 and 1.000 (p < 0.001 in all cases). Moreover, χ2 tests revealed significant association between instrument families and seated posture with respect to pelvic attitude, dorsal curvature and head alignment in both sagittal and frontal planes. This analysis also showed an association between instrument families and standing posture with respect to the frontal plane of the axis of gravity, pelvic attitude, head alignment in the frontal plane, the sagittal plane of the shoulders and overall posture. CONCLUSIONS: While certain postural defects appear to be common to all families of instruments, others are more characteristic of some families than others. The instrument associated with the best posture quality was the bagpipe, followed by percussion and strings.

Deep versus moderate neuromuscular block during one-lung ventilation in lung resection surgery / Bloqueio neuromuscular profundo versus moderado durante a ventilação monopulmonar em cirurgia de ressecção pulmonar

Abstract Background and objectives: Neuromuscular relaxants are essential during general anesthesia for several procedures. Classical anesthesiology literature indicates that the use of neuromuscular blockade in thoracic surgery may be deleterious in patients in lateral decubitus position in one-lung ventilation. The primary objective of our study was to compare respiratory function according to the degree of patient neuromuscular relaxation. Secondary, we wanted to check that neuromuscular blockade during one-lung ventilation is not deleterious. Methods: A prospective, longitudinal observational study was made in which each patient served as both treated subject and control. 76 consecutive patients programmed for lung resection surgery in Gregorio Marañon Hospital along 2013 who required one-lung ventilation in lateral decubitus were included. Ventilator data, hemodynamic parameters were registered in different moments according to train-of-four response (intense, deep and moderate blockade) during one-lung ventilation. Results: Peak, plateau and mean pressures were significantly lower during the intense and deep blockade. Besides compliance and peripheral oxygen saturation were significantly higher in that moments. Heart rate was significantly higher during deep blockade. No mechanical ventilation parameters were modified during measurements. Conclusions: Deep neuromuscular blockade attenuates the poor lung mechanics observed during one-lung ventilation.

Resumo Justificativa e objetivos: Os relaxantes neuromusculares são essenciais durante a anestesia geral para vários procedimentos. A literatura clássica de anestesiologia indica que o uso de bloqueio neuromuscular em cirurgia torácica pode ser prejudicial em pacientes posicionados em decúbito lateral com ventilação seletiva. O objetivo primário deste estudo foi comparar a função respiratória de acordo com o grau de relaxamento neuromuscular do paciente. O objetivo secundário foi verificar que o bloqueio neuromuscular durante a ventilação seletiva não é prejudicial. Métodos: Estudo observacional, prospectivo e longitudinal no qual cada paciente serviu como próprio controle. Foram incluídos 76 pacientes consecutivos, agendados para cirurgia de ressecção do pulmão no Hospital Gregorio Marañon ao longo de 2013, submetidos à ventilação seletiva em decúbito lateral. Os dados do ventilador e os parâmetros hemodinâmicos foram registrados em diferentes momentos de acordo com a resposta por sequência de quatro estímulos (bloqueio intenso, profundo e moderado) durante a ventilação seletiva. Resultados: As pressões de pico, platô e média foram significativamente menores durante os bloqueios intenso e profundo. Além disso, complacência e saturação periférica de oxigênio foram significativamente maiores nesses momentos. A frequência cardíaca foi significativamente maior durante o bloqueio profundo. Não houve alteração dos parâmetros da ventilação mecânica durante as mensurações. Conclusões: O bloqueio neuromuscular profundo atenua a mecânica pulmonar deficiente observada durante a ventilação seletiva.

[Deep versus moderate neuromuscular block during one-lung ventilation in lung resection surgery]. / Bloqueio neuromuscular profundo versus moderado durante a ventilação monopulmonar em cirurgia de ressecção pulmonar.

BACKGROUND AND OBJECTIVES: Neuromuscular relaxants are essential during general anesthesia for several procedures. Classical anesthesiology literature indicates that the use of neuromuscular blockade in thoracic surgery may be deleterious in patients in lateral decubitus position in one-lung ventilation. The primary objective of our study was to compare respiratory function according to the degree of patient neuromuscular relaxation. Secondary, we wanted to check that neuromuscular blockade during one-lung ventilation is not deleterious. METHODS: A prospective, longitudinal observational study was made in which each patient served as both treated subject and control. 76 consecutive patients programmed for lung resection surgery in Gregorio Marañon Hospital along the year of 2013 who required one-lung ventilation in lateral decubitus were included. Ventilator data, hemodynamic parameters were registered in different moments according to train-of-four response (intense, deep and moderate blockade) during one-lung ventilation. RESULTS: Peak, plateau and mean pressures were significantly lower during the intense and deep blockade. Besides, compliance and peripheral oxygen saturation were significantly higher in those moments. Heart rate was significantly higher during deep blockade. No mechanical ventilation parameters were modified during measurements. CONCLUSIONS: Deep neuromuscular blockade attenuates the poor lung mechanics observed during one-lung ventilation.