Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

STABILITÀ E EFFICIENZA DELLE CELLE SOLARI ELETTROCHIMICHE A COLORANTE - DSC

Lo sviluppo negli ultimi 20 anni delle ricerche sulle celle solari a colorante (dye-sensitized-cells, DSC) è stato spettacolare, se consideriamo l’efficienza e la superficie attiva della prima cella [1], rispetto a quelle delle celle DSC di oggi. In tutti questi anni, tuttavia, sono stati pochi gli studi riguardanti la stabilità della cella in condizioni di operazione, sotto illuminazione solare vera o simulata [2]. In passato abbiamo già notato il ruolo cruciale che svolge l’elettrolita redox nel determinare la corrente limite di cella [3] e, possibilmente, la sua decrescita graduale nel tempo. Nel nostro recente lavoro abbiamo dimostrato che la degradazione delle proprietà di cella è fortemente correlata con l’azione del mediatore redox a base di iodio/ioduro. Abbiamo analizzato, a tale scopo, il comportamento di celle con area rettangolare (1 cm x 4 cm), irraggiate a lungo (fino a 3600 h) sia in laboratorio sia sotto luce naturale [4]. Le condizioni di lavoro (temperatura, inclinazione della cella, resistenza di carico) sono state accuratamente vagliate, per poter stabilire i principali fattori di perdita di efficienza di conversione solare, che vanno da un minimo di 0.8% annuo, fino a un massimo di oltre 9% annuo, per celle DSC identiche, tutte con efficienza iniziale del 5%. Presenteremo in questo lavoro una serie di risultati di misure di impedenza elettrochimica (EIS) e di trasmittanza ottica dell’elettrolita, la cui analisi rivela che i due parametri di cella che diminuiscono maggiormente con il tempo di operazione sono la resistenza di ricombinazione e il tempo di vita del fotoelettrone, mentre invece aumenta la resistenza di diffusione dell’elettrolita redox. Discuteremo quindi le prospettive di applicazione su larga scala delle celle DSC, tenendo conto delle conclusioni di questo studio

External validation of unsupervised COVID-19 clinical phenotypes and their prognostic impact

AbstractBackground Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis.Methods Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method.Results Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81–5.30, p < 0.001) and for phenotype C vs. B (HR 2.20, 95% CI 1.50–3.23, p < 0.001). A non-statistically significant trend towards higher mortality was also observed for phenotype B vs. A (HR 1.41; 95% CI 0.92–2.15, p = 0.115). By means of cluster analysis, three different phenotypes were also identified in our cohort, with an overall similar gradient in terms of prognostic impact to that observed when patients were assigned to FEN-COVID-19 phenotypes.Conclusions The prognostic impact of FEN-COVID-19 phenotypes was confirmed in our external cohort, although with less difference in mortality between phenotypes A and B than in the original study

T2Bacteria and T2Resistance Assays in Critically Ill Patients with Sepsis or Septic Shock: A Descriptive Experience

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested with the T2Bacteria and T2Resistance assays were included in a retrospective, single center study. The primary descriptive endpoints were results of rapid molecular tests and concomitant blood cultures. Overall, 38 combinations of T2Bacteria and T2Resistance tests were performed. One or more causative agent(s) were identified by the T2Bacteria assay in 26% of episodes (10/38), whereas negative and invalid results were obtained in 66% (25/38) and 8% (3/38) of episodes, respectively. The same pathogen detected by the T2Bacteria test grew from blood cultures in 30% of cases (3/10). One or more determinant(s) of resistance were identified by the T2Resistance assay in 11% of episodes (4/38). Changes in therapy based on T2Bacteria and/or T2Resistance results occurred in 21% of episodes (8/38). In conclusion, T2Bacteria/T2Resistance results can influence early treatment decisions in critically ill patients with sepsis or septic shock in real-life practice. Large, controlled studies remain necessary to confirm a favorable impact on patients’ outcomes and antimicrobial stewardship interventions

External validation of unsupervised COVID-19 clinical phenotypes and their prognostic impact

Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis. Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method. Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81–5.30, p p p = 0.115). By means of cluster analysis, three different phenotypes were also identified in our cohort, with an overall similar gradient in terms of prognostic impact to that observed when patients were assigned to FEN-COVID-19 phenotypes. The prognostic impact of FEN-COVID-19 phenotypes was confirmed in our external cohort, although with less difference in mortality between phenotypes A and B than in the original study. Hospitalized patients with COVID-19 can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory featuresIn this study, we externally confirmed the prognostic impact of clinical phenotypes previously identified by Gutierrez-Gutierrez and colleagues in a Spanish cohort of hospitalized patients with COVID-19, and the usefulness of their simplified probabilistic model for phenotypes assignmentThis could indirectly support the validity of both phenotype’s development and their extrapolation to other hospitals and countries for management decisions during other possible future viral pandemics Hospitalized patients with COVID-19 can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features In this study, we externally confirmed the prognostic impact of clinical phenotypes previously identified by Gutierrez-Gutierrez and colleagues in a Spanish cohort of hospitalized patients with COVID-19, and the usefulness of their simplified probabilistic model for phenotypes assignment This could indirectly support the validity of both phenotype’s development and their extrapolation to other hospitals and countries for management decisions during other possible future viral pandemics</p

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50\ue2\u80\u9375 years with type 2 diabetes inadequately controlled with metformin monotherapy (2\ue2\u80\u933 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15\ue2\u80\u9345 mg) or a sulfonylurea (5\ue2\u80\u9315 mg glibenclamide, 2\ue2\u80\u936 mg glimepiride, or 30\ue2\u80\u93120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57\uc2\ub73 months. The primary outcome occurred in 105 patients (1\uc2\ub75 per 100 person-years) who were given pioglitazone and 108 (1\uc2\ub75 per 100 person-years) who were given sulfonylureas (hazard ratio 0\uc2\ub796, 95% CI 0\uc2\ub774\ue2\u80\u931\uc2\ub726, p=0\uc2\ub779). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p&lt;0\uc2\ub70001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. Interpretation In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. Funding Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society

Prosafe: a european endeavor to improve quality of critical care medicine in seven countries

BACKGROUND: long-lasting shared research databases are an important source of epidemiological information and can promote comparison between different healthcare services. Here we present ProsaFe, an advanced international research network in intensive care medicine, with the focus on assessing and improving the quality of care. the project involved 343 icUs in seven countries. all patients admitted to the icU were eligible for data collection. MetHoDs: the ProsaFe network collected data using the same electronic case report form translated into the corresponding languages. a complex, multidimensional validation system was implemented to ensure maximum data quality. individual and aggregate reports by country, region, and icU type were prepared annually. a web-based data-sharing system allowed participants to autonomously perform different analyses on both own data and the entire database. RESULTS: The final analysis was restricted to 262 general ICUs and 432,223 adult patients, mostly admitted to Italian units, where a research network had been active since 1991. organization of critical care medicine in the seven countries was relatively similar, in terms of staffing, case mix and procedures, suggesting a common understanding of the role of critical care medicine. conversely, icU equipment differed, and patient outcomes showed wide variations among countries. coNclUsioNs: ProsaFe is a permanent, stable, open access, multilingual database for clinical benchmarking, icU self-evaluation and research within and across countries, which offers a unique opportunity to improve the quality of critical care. its entry into routine clinical practice on a voluntary basis is testimony to the success and viability of the endeavor

Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: post-hoc analysis of LAS VEGAS study

Background: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. Methods: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. Results: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. Conclusions: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs

Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications

Background: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). Methods: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8: 00 AM and 7: 59 PM, and as 'night-time' when induction was between 8: 00 PM and 7: 59 AM. Results: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P = 0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P = 0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P = 0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P = 0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P = 0.15). Conclusions: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events