Variables predicting weaning outcome in prolonged mechanically ventilated tracheotomized patients: a retrospective study

Background: Several studies have assessed predictors of weaning and extubation outcome in short-term mechanically ventilated patients, but there are only few studies on predictors of weaning from prolonged mechanical ventilation. Methods: Retrospective, single-center, observational study at a specialized national weaning center in Germany. Patients' medical records were reviewed to obtain data on demographics, comorbidities, respiratory indices, and the result of a prospectively documented, standardized spontaneous breathing trial (SBT) upon admission to the weaning center. Respiratory indices assessed were the ventilatory ratio (VR) and parameters derived from calculated mechanical power (MP). Predictors associated with failure of prolonged weaning and failure of the SBT were assessed using a binary logistic regression model. Results: A total of 263 prolonged mechanically ventilated, tracheotomized patients, treated over a 5-year period were analyzed. After 3 weeks of mechanical ventilation, patients with unsuccessful weaning failed a SBT more frequently and showed significantly increased values for inspiratory positive airway pressure, driving pressure, VR, absolute MP, and MP normalized to predicted body weight and dynamic lung-thorax compliance (LTC-MP). In the logistic regression analyses, variables independently correlated with weaning failure were female gender (adjusted odds ratio 0.532 95% CI 0.291-0.973; p = 0.040), obesity (body mass index ≥ 30 kg/m2) (2.595 1.210-5.562; p = 0.014), COPD (3.209 1.563-6.589; p = 0.002), LTC-MP (3.470 1.067-11.284; p = 0.039), PaCO2 on mechanical ventilation (1.101 95% CI 1.034-1.173; p = 0.003), and failure of the SBT (4.702 2.250-9.825; p < 0.001). In addition, female gender (0.401 0.216-0.745; p = 0.004), LTC-MP (3.017 1.027-8.862; p = 0.046), and PaCO2 on mechanical ventilation (1.157 1.083-1.235; p < 0.001) were independent risk factors for an unsuccessful SBT. Conclusions In the present study, the derived predictors of weaning point to a crucial role of the workload imposed on respiratory muscles during spontaneous breathing. Mechanical power normalized to lung-thorax compliance was independently correlated with weaning outcome and may identify patients at high risk for weaning failure

A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation

Bronchiolitis obliterans; Clinical research; Lung transplantationBronquiolitis obliterante; Investigación clínica; Trasplante de pulmónBronquiolitis obliterant; Recerca clínica; Trasplantament de pulmóLong-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6–32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.The study was funded by PARI Pharma GmbH. Open access funding enabled and organized by ProjektDEAL

Impact of Lung Function Decline on Mortality in Lung Transplant Recipients: Long-Term Results From the L-CsA-i Study for the Prevention of Bronchiolitis Obliterans Syndrome

Cyclosporine (CsA); Chronic rejection; Lung transplantationCiclosporina (CsA); Rechazo crónico; Trasplante de pulmónCiclosporina (CsA); Rebuig crònic; Trasplantament de pulmóBackground: Chronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx). Methods: 10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis. Results: A total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality (p < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk. Conclusion: Based on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions.This study was funded by Zambon S.p.A., Milan, Italy

Artichoke deep learning detection network for site-specific agrochemicals UAS spraying

Abstract Input optimization is a distinguishing characteristic of Precision Agriculture approaches, helping reduce the environmental impact and costs and increase vegetable production quality. Thanks to the high automation evolution of Unmanned Aerial Systems (UAS), a new approach derived from their combination with Deep Learning techniques is leading to significant improvements in agricultural management practices. The study aims at artichoke plants detection and georeferencing as a first step for an on-the-fly, real time, UAS spraying system, and use the gathered information to monitor crop development through a multi-temporal approach. A commercial UAS, equipped with an RGB sensor, acquired images of the artichoke field located in Sardinia (Italy) during the 2021–2022 season in different crop growth stages. The FPN (Feature Pyramid Network), trained and compared with the YOLOv5 (You Only Look Once) network, showed a high detection level with an average F1 score of around 90%, and satisfactory off-line performances on the Nvidia Jetson Nano board. YOLOv5 achieved the best overall result. The FPN recorded a lower recall, which is desirable to achieve a minimum number of detection errors and limit the leakage of agrochemicals on false-positive targets. The multi-temporal approach influenced detection performances, with an inverse response of precision and recall metrics. The growing index trend showed a distinct value in October, peaking at the beginning of December as expected. The proposed approach contributes to designing future automatic and reliable site-specific UAS agrochemicals application and the classification of management zones

Population Data for Y-Chromosome Haplotypes Defined by AmpFlSTR YFiler PCR Amplification Kit in North Sardinia (Italy)

The 17 Y-chromosomal short tandem repeats (STRs) included in the AmpFlSTR YFiler Amplification Kit (AB Applied Biosystems) (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.1) were typed in 100 samples from North Sardinia (Italy). A total of 91 different haplotypes were found, where 9 haplotypes were shared by two individuals. The overall haplotype diversity (HD) was 0.9982. DYS458 non-consensus alleles were found in one samples, and one in the DYS438. We found a double peak in one sample for the DYS19 with alleles 15/16. Population comparisons with available 10 YSTR loci data in Mediterranean Basin samples were undertaken, significant differences were observed between our sample and all the compared populations, except for a entire sample from Sardinia. Prediction of haplogroups showed I2a1 was found to be the most frequent haplogroup (33%) in our sample. Testing high-resolution Y-chromosome data sets it is useful in autochthonous population and micro-population studies to highlight the most informative loci for evolutionary aims

Mechanical power density predicts prolonged ventilation following double lung transplantation

Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman’s coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman’s ρ = 0.252 [95% CI 0.129–0.369], p < 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation (ρ = 0.452 [0.345–0.548], p < 0.01) and enhancing PMV prediction (AUROC 0.78 [95% CI 0.72–0.83], p < 0.01) compared to MP (AUROC 0.66 [0.60–0.72], p < 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation

Population Data for Y-Chromosome Haplotypes Defined by AmpFlSTR YFiler PCR Amplification Kit in North Sardinia (Italy)

The 17 Y-chromosomal short tandem repeats (STRs) included in the AmpFlSTR YFiler Amplification Kit (AB Applied Biosystems) (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.1) were typed in 100 samples from North Sardinia (Italy). A total of 91 different haplotypes were found, where 9 haplotypes were shared by two individuals. The overall haplotype diversity (HD) was 0.9982. DYS458 non-consensus alleles were found in one samples, and one in the DYS438. We found a double peak in one sample for the DYS19 with alleles 15/16. Population comparisons with available 10 YSTR loci data in Mediterranean Basin samples were undertaken, significant differences were observed between our sample and all the compared populations, except for a entire sample from Sardinia. Prediction of haplogroups showed I2a1 was found to be the most frequent haplogroup (33%) in our sample. Testing high-resolution Y-chromosome data sets it is useful in autochthonous population and micro-population studies to highlight the most informative loci for evolutionary aims

Impact of Lung Function Decline on Mortality in Lung Transplant Recipients: Long-Term Results From the L-CsA-i Study for the Prevention of Bronchiolitis Obliterans Syndrome

BackgroundChronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx). Methods10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis. ResultsA total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality (p < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk. ConclusionBased on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions

Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity

OBJECTIVE Evaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors. METHODS Patients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4~months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function. RESULTS 76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate-severe disease. After 4~months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p 3~mmHg during cycle exercise occurred in 1/5 of patients after mild disease course. CONCLUSION We characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition