Software-guided (PREVEDEL) cognitive stimulation to prevent delirium in hospitalised older adults: study protocol.

BACKGROUND: Delirium is a clinical condition characterised by acute and fluctuating deterioration of the cognitive state, generally secondary to an acute pathology. Delirium is associated with negative outcomes in older adults, such as longer hospitalisations, higher mortality, and short and medium-term institutionalisation. Randomised clinical trials have shown that delirium is preventable through non-pharmacological prevention measures, decreasing its incidence by 30-50%. These interventions include promoting physical activity, facilitating the use of glasses and hearing aids, cognitive stimulation, and providing frequent reorientation of time and space, among others. These measures are currently seldom applied in hospitals in Chile and around the world for reasons including the heavy workload of clinical staff, the lack of trained personnel, and in general the absence of a systematic implementation processes. We developed a software called PREVEDEL, which includes non-pharmacological strategies such as cognitive stimulation, early mobilisation, orientation, and pain assessment. We propose a randomised clinical trial to evaluate whether cognitive stimulation guided by PREVEDEL software prevents delirium status (full/subsyndromal delirium) in hospitalised older adults. METHOD: A randomised controlled trial, with parallel, multicentre groups. We will recruite patients 65 years or older who have been hospitalised for less than 48 h in the general ward or the intermediate care units of four hospitals in Santiago, Chile. The participants in the intervention group will use a tablet with cognitive stimulation software for delirium prevention for five continuous days versus the control group who will use the tablet without the software. We will evaluate the incidence, duration, density of delirium, subsyndromal delirium with the Confusion Assessment Method, cognitive with the Montreal Cognitive Assessment, and functional status with the Functional Independence Measure at discharge. Moreover, we will evaluate the adherence to prevention measures, as well as demographic variables of interest. DISCUSSION: The use of cognitive PREVEDEL software could increase and improve the implementation of non-pharmacological prevention measures for delirium in hospitalised older adults, thus reducing its incidence and contributing to patients and health professionals. TRIAL REGISTRATION: NCT05108207 ClinicalTrials.gov. Registered 4 November 2021.

Mortality in patients with severe COVID-19 who underwent tracheostomy due to prolonged mechanical ventilation.

BACKGROUND: The usefulness of tracheostomy has been questioned in patients with COVID-19 and prolonged invasive mechanical ventilation (IMV). AIM: To compare the 90-day mortality rate of patients who underwent a tracheostomy due prolonged IMV with those that did not receive this procedure. MATERIAL AND METHODS: We studied a historical cohort of 92 patients with COVID-19 and prolonged IMV (> 10 days). The primary outcome was the 90-day mortality rate. Secondary outcomes included days on IMV, hospital/intensive care unit (ICU) length of stay, frequency of nosocomial infections, and thrombotic complications demonstrated by images. A logistic regression was performed to adjust the effect of tracheostomy by SOFA score and days on IMV. RESULTS: Forty six patients aged 54 to 66 years (72% males) underwent tracheostomy. They had a median of two comorbidities, and received the procedure after a median of 20.5 days on IMV (interquartile range: 17-26). 90-day mortality was lower in patients who were tracheostomized than in the control group (6.5% vs. 32.6%, p-value < 0.01). However, after controlling for confounding factors, no differences were found in mortality between both groups (relative risk = 0.303, p-value = 0.233). Healthcare-associated infections and hospital/ICU length of stay were higher in patients with tracheostomy than in controls. Thrombotic complications occurred in 42.4% of the patients, without differences between both groups. No cases of COVID-19 were registered in the healthcare personnel who performed tracheostomies. CONCLUSIONS: In patients with COVID-19 undergoing prolonged IMV, performing a tracheostomy is not associated with excess mortality, and it is a safe procedure for healthcare personnel.

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof-of-concept study.

RATIONALE: Cyclic strain may be a determinant of ventilator-induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (StrainCT ). OBJECTIVES: To compare the global StrainCT with the change in electrical impedance (ΔZ). METHODS: Acute respiratory distress syndrome patients under mechanical ventilation (VT 6 mL/kg ideal body weight with positive end-expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole-lung CT at end-inspiration and end-expiration. Biomechanical analysis was used to construct 3D maps and determine StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ. MAIN RESULTS: StrainCT was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P < .001 at global level) with a high agreement between predicted and measured StrainCT . CONCLUSIONS: The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.

[Analgesia, sedation, neuromuscular blockade and delirium management practices in Chilean intensive care units]. / Prácticas nacionales de analgesia, sedación y delirium en las Unidades de Cuidados Intensivos de adultos en Chile.

BACKGROUND: The appropriate use of analgesia, sedation, neuromuscular blockade and the diagnosis and prevention of delirium (ASBD) are associated with better outcomes in critically ill patients at Intensive Care Unit (ICUs). AIM: To know the practices about analgesia, sedation, delirium, and neuromuscular blockade use among healthcare professionals working in adult ICUs in Chile. MATERIAL AND METHODS: An electronic survey was sent to 812 professionals working in ICUs using a previously published instrument, which was adapted and authorized by the author. RESULTS: We received 278 surveys. Fifty two percent of respondents were physicians, 34% nurses and 11% physical therapists. Their age ranged between 30 and 39 years in 43% and was over 50 years in 9%. Eighty four percent evaluated pain routinely, but only 26% use a validated scale. Sedation was routinely evaluated with a validated scale and 73% referred to have a protocol. Neuromuscular block is seldom used, and little monitoring occurs (43%). Delirium is routinely evaluated by 48% of respondents, usually using the CAM-ICU scale. CONCLUSIONS: There is a heterogeneous adherence to the ASBD recommended practices. The main gaps are in the assessment of pain, monitoring of neuromuscular blockade and diagnosis of delirium through validated instruments.

Cyanobacteria and Eukaryotic Microalgae as Emerging Sources of Antibacterial Peptides.

Cyanobacteria and microalgae are oxygen-producing photosynthetic unicellular organisms encompassing a great diversity of species, which are able to grow under all types of extreme environments and exposed to a wide variety of predators and microbial pathogens. The antibacterial compounds described for these organisms include alkaloids, fatty acids, indoles, macrolides, peptides, phenols, pigments and terpenes, among others. This review presents an overview of antibacterial peptides isolated from cyanobacteria and microalgae, as well as their synergism and mechanisms of action described so far. Antibacterial cyanopeptides belong to different orders, but mainly from Oscillatoriales and Nostocales. Cyanopeptides have different structures but are mainly cyclic peptides. This vast peptide repertoire includes ribosomal and abundant non-ribosomal peptides, evaluated by standard conventional methodologies against pathogenic Gram-negative and Gram-positive bacteria. The antibacterial activity described for microalgal peptides is considerably scarcer, and limited to protein hydrolysates from two Chlorella species, and few peptides from Tetraselmis suecica. Despite the promising applications of antibacterial peptides and the importance of searching for new natural sources of antibiotics, limitations still persist for their pharmaceutical applications.

Cyanobacterial peptides as a tour de force in the chemical space of antiparasitic agents.

Parasites are scarcely addressed target for antimicrobial peptides despite their big impact in health and global economy. The notion of antimicrobial peptides is frequently associated to the innate immune defense of vertebrates and invertebrate vectors, as the ultimate recipients of the parasite infection. These antiparasite peptides are produced by ribosomal synthesis, with few post-translational modifications, and their diversity come mostly from their amino acid sequence. For many of them permeabilization of the cell membrane of the targeted pathogen is crucial for their microbicidal mechanism. In contrast, cyanobacterial peptides are produced either by ribosomal or non-ribosomal biosynthesis. Quite often, they undergo heavy modifications, such as the inclusion of non-proteinogenic amino acids, lipid acylation, cyclation, Nα-methylation, or heterocyclic rings. Furthermore, the few targets identified for cyanobacterial peptides in parasites are intracellular. Some cyanobacterial antiparasite peptides are active at picomolar concentrations, whereas those from higher eukaryotes usually work in the micromolar range. In all, cyanobacterial peptides are an appealing target to develop new antiparasite therapies and a challenge in the invention of new synthetic methods for peptides. This review aims to provide an updated appraisal of antiparasite cyanobacterial peptides and to establish a side-by -side comparison with those antiparasite peptides from higher eukaryotes.

Identification of Antimicrobial Peptides from the Microalgae Tetraselmis suecica (Kylin) Butcher and Bactericidal Activity Improvement.

The outburst of microbial resistance to antibiotics creates the need for new sources of active compounds for the treatment of pathogenic microorganisms. Marine microalgae are of particular interest in this context because they have developed tolerance and defense strategies to resist the exposure to pathogenic bacteria, viruses, and fungi in the aquatic environment. Although antimicrobial activities have been reported for some microalgae, natural algal bioactive peptides have not been described yet. In this work, acid extracts from the microalga Tetraselmis suecica with antibacterial activity were analyzed, and de novo sequences of peptides were determined. Synthetic peptides and their alanine and lysine analogs allowed identifying key residues and increasing their antibacterial activity. Additionally, it was determined that the localization of positive charges within the peptide sequence influences the secondary structure with tendency to form an alpha helical structure.

Evidence for the facultative intracellular behaviour of the fish pathogen Vibrio ordalii.

Vibrio ordalii is an extracellular, Gram-negative bacterium that produces vibriosis in salmonids. While pathogenesis is not fully understood, this bacterium has numerous likely genes for adhesion, colonization, invasion factors and, as recently suggested, intracellular behaviour. Therefore, this study aimed to clarify possible intracellular behaviour for V. ordalii Vo-LM-18 and ATCC 33509T in the fish-cell lines SHK-1 and CHSE-214. Confocal microscopy revealed Vo-LM-18 and ATCC 33509T inside cytoplasm in both fish-cell lines at 4 hr post-inoculation (hpi). At 8 and 16 hpi, the proportion of fish cells invaded by both strains increased. Moreover, intracellular V. ordalii were observed after 8 hpi inside mouse embryonic fibroblasts (MEF), demonstrating that entry was not due to a cellular phagocytosis process. Flow cytometry confirmed immunocytochemistry results, with both V. ordalii evidencing statistically significant differences in the number of infected cells between 8 and 16 hpi. Interestingly, V. ordalii infection did not significantly damage fish cells, as determined by LDH liberation. Viable counts at 8 hpi detected, on average for both lines, 176 ± 47 CFU/ml of culturable intracellular Vo-LM-18 and ATCC 33509T cells. These in vitro findings support the facultative intracellular behaviour of V. ordalii and may be of importance for understanding pathogenicity and survival in aquatic environments.

Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers.

OBJECTIVE: To determine the feasibility and clinical utility of using comprehensive genomic profiling (CGP) in the course of clinical care to identify clinically relevant tumor genomic alterations for patients with either rare or refractory gynecologic cancers to facilitate point-of-care management. Use of an expert, multidisciplinary, institutional molecular tumor board (MTB) assessment is discussed regarding input on putative targeted options for individualized therapy. METHODS: A prospective clinical trial is ongoing. We report on the initial 69 patients with gynecologic cancers that were either rare or refractory to standard therapy. CGP was performed by Foundation Medicine, Inc. Genomic alterations were reviewed by members of an MTB. Consensus recommendations on genomically targeted, FDA-approved, on- and off-label therapies and clinical trials were sent to the treating physician, and decisions and outcomes were assessed. RESULTS: Study outcomes were available for 64 patients. The mean number of genes altered per tumor was 4.97 (median=4; range, 1-26), and the average turnaround time from testing laboratory report to generation of formal recommendations was approximately three weeks. Evaluation of genomic and clinical data by the MTB led to generation of targeted treatment options in all 64 patients, and the percentage of patients for whom one or more of these recommendations were implemented by the treating physician was 39%. Sixty-four percent of the patients receiving targeted therapy based on a CGP result experienced radiologic response or showed evidence of clinical benefit or stable disease. CONCLUSION: These data suggest that an institutional MTB is a feasible venue for reviewing tumor genomic profiling results and generating clinical recommendations. These data also support the need for further studies and guidelines on clinical decision making with greater availability of broad genomically based diagnostics.

Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment.

Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease.

[Alcohol consumption among traveling Chilean older people]. / Consumo de alcohol en el adulto mayor chileno que viaja.

BACKGROUND: Problems associated with alcohol consumption are prevalent in Chile, but little is known about the situation in the elderly. AIM: To perform a screening to detect alcohol-related problems and risks in the Chilean older people who travel. MATERIAL AND METHODS: The Alcohol Use Disorders Identification Test (AUDIT) questionnaire was answered by 1,076 travelers aged 60 to 93 years (66% females), who participated in trips organized by the Chilean National Tourism Service (SERNATUR). RESULTS: Seventy six percent of respondents acknowledged to have ingested an alcoholic drink during the last month. The average AUDIT score was of 2.2 ± 2.6. Only 3.7% of the sample had a score equal or higher than eight, considered as risky use. Within this last group, 60% had symptoms of alcohol dependence. A higher alcohol consumption was associated with male gender (p < 0.01), being younger than 75 years of age (p < 0.01), having a medium-low economic income (p < 0.01) and having a higher education level (p = 0.03). There was no significant association with the respondents' occupation. CONCLUSIONS: In this sample of Chilean traveling older people, there was a high prevalence of alcohol consumption, and nearly 4% of respondents had alcohol related problems.

Chile's agricultural research institute plant tissue analysis dataset.

This dataset holds 9,175 entries that report the nitrogen, phosphorus, potassium, calcium, magnesium, zinc, manganese, copper and boron contents of various plant species, with a focus on crops. The dataset accounts data of 94 plant species, and present nutrient concentration of 14 different plant tissues. The data are derived from the Soil and Plant Nutrition Lab of the Chilean Agricultural Research Institute, which provided services to farmers in the Chilean Central Valley between 2006 and 2020. The analytical methods used to generate these data were consistent across all years, ensuring the reliability of the information. Specifically, nitrogen content was determined using the Kjeldahl method, while all other analytes were quantified via colorimetry (phosphorus and boron) or atomic absorption spectrometry following high-temperature oxidation and dilution of the ashes with hydrochloric acid. The dataset has numerous potential applications, including the estimation of crop nutrient extraction rates, the identification of nutrient deficiencies or excesses, and the provision of reference or prior information for researchers studying plant physiology. The dataset includes 21 Chilean endemic species, which might be of particular interest to researchers studying the biodiversity and ecology of Chile's Central Valley.

Considerations and analysis of the implementation of oncogeriatrics in Chile and its importance: Review of current literature.

The Chilean census of 2017 reported that 11.4% of the local population are 65 years or older, and according to the National Institute of Statistics (INE) the current expectancy of life in Chile is 76 years for men and 81 years for women respectively. Cancer in Chile is a major public health problem. Aging is a significant risk factor for cancer development which added to the improved life expectancy, it increases the incidence of cancer. In 2040, new cancer cases will increase from 19.3 to 30.2 million worldwide. Older people are a heterogeneous group requiring specialized and individualized management. Chronological age does not necessarily correlate with physiological age. More than half of the geriatric patients with cancer have at least one comorbidity which is relevant when defining a cancer treatment. Likewise, polypharmacy is frequent and is an important issue to consider in people with cancer due to the risk associated with drug interactions. Oncogeriatric assessment consists of a comprehensive multidimensional evaluation, including functional and biopsychosocial issues, addressing aspects of the neoplastic disease such as the risk of toxicities due to systemic therapy and life expectancy. This tool has proven to be helpful in the diagnosis of conditions that are not evident in a routine oncological evaluation, such as geriatric syndromes, frailty, functional dependence, and cognitive impairment among others, which have an impact when deciding on therapy, predicting risks of treatment toxicity and mortality. In this article we aim to describe the current situation of Oncogeriatrics and to provide epidemiological information about cancer in the elderly population in Chile attempting to highlight the importance of the Oncogeriatrics units, within cancer departments, for a better decision taking in the elderly cancer patient.

Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?

Trypanosomiases are a group of tropical diseases that have devastating health and socio-economic effects worldwide. In humans, these diseases are caused by the pathogenic kinetoplastids Trypanosoma brucei, causing African trypanosomiasis or sleeping sickness, and Trypanosoma cruzi, causing American trypanosomiasis or Chagas disease. Currently, these diseases lack effective treatment. This is attributed to the high toxicity and limited trypanocidal activity of registered drugs, as well as resistance development and difficulties in their administration. All this has prompted the search for new compounds that can serve as the basis for the development of treatment of these diseases. Antimicrobial peptides (AMPs) are small peptides synthesized by both prokaryotes and (unicellular and multicellular) eukaryotes, where they fulfill functions related to competition strategy with other organisms and immune defense. These AMPs can bind and induce perturbation in cell membranes, leading to permeation of molecules, alteration of morphology, disruption of cellular homeostasis, and activation of cell death. These peptides have activity against various pathogenic microorganisms, including parasitic protists. Therefore, they are being considered for new therapeutic strategies to treat some parasitic diseases. In this review, we analyze AMPs as therapeutic alternatives for the treatment of trypanosomiases, emphasizing their possible application as possible candidates for the development of future natural anti-trypanosome drugs.

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort.

End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response in vivo and in vitro. Increased FGF23 levels associate with higher infection-related hospitalizations and adverse infectious outcomes. Thus, we evaluated whether ESRD patients with high FGF23 titers have an increased rate of SARS-CoV-2 infection. METHODS: We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. RESULTS: We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03-3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. DISCUSSION: Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort.

Acute Kidney Injury (AKI) is a frequent complication in intensive care unit (ICU) patients that increases mortality and chronic kidney disease (CKD) development. AKI is associated with elevated plasma fibroblast growth factor 23 (FGF23), which can be modulated by erythropoietin (EPO) and Klotho. We aimed to evaluate whether a combined biomarker that includes these molecules predicted short-/long-term outcomes. We performed a prospective cohort of ICU patients with sepsis and previously normal renal function. They were followed during their inpatient stay and for one year after admission. We measured plasma FGF23, EPO, and Klotho levels at admission and calculated a combined biomarker (FEK). A total of 164 patients were recruited. Of these, 50 (30.5%) had AKI at admission, and 55 (33.5%) developed AKI within 48 h. Patients with AKI at admission and those who developed AKI within 48 h had 12- and 5-fold higher FEK values than non-AKI patients, respectively. Additionally, patients with higher FEK values had increased 1-year mortality (41.9% vs. 18.6%, p = 0.003) and CKD progression (26.2% vs. 8.3%, p = 0.023). Our data suggest that the FEK indicator predicts the risk of AKI, short-/long-term mortality, and CKD progression in ICU patients with sepsis. This new indicator can improve clinical outcome prediction and guide early therapeutic strategies.

Non-pharmacological prevention of postoperative delirium by occupational therapy teams: A randomized clinical trial.

Background: Patients who develop postoperative delirium (POD) have several clinical complications, such as increased morbidity, increased hospital stays, higher hospital costs, cognitive and functional impairment, and higher mortality. POD is a clinical condition preventable by standard non-pharmacological measures An intensive Occupational Therapy (OT) intervention has been shown to be highly effective in preventing delirium in critically ill medical patients, but it is unknown the effect in surgical patients. Thus, we designed a prospective clinical study with the aim to determine whether patients undergoing intervention by the OT team have a lower incidence of POD compared to the group treated only with standard measures. Methods: A multicenter, single-blind, randomized clinical trial was conducted between October 2018 and April 2021, in Santiago of Chile, at a university hospital and at a public hospital. Patients older than 75 years undergoing elective major surgery were eligible for the trial inclusion. Patients with cognitive impairment, severe communication disorder and cultural language limitation, delirium at admission or before surgery, and enrolled in another study were excluded. The intervention consisted of OT therapy twice a day plus standard internationally recommended non-pharmacological prevention intervention during 5 days after surgery. Our primary outcome was development of delirium and postoperative subsyndromal delirium. Results: In total 160 patients were studied. In the interventional group, treated with an intensive prevention by OT, nine patients (12.9%) developed delirium after surgery and in the control group four patients (5.5%) [p = 0.125, RR 2.34 CI 95 (0.75-7.27)]. Whereas subsyndromal POD was present in 38 patients in the control group (52.1%) and in 34 (48.6%) in the intervention group [p = 0.4, RR 0.93 CI95 (0.67-1.29)]. A post hoc analysis determined that the patient's comorbidity and cognitive status prior to hospitalization were the main risk factors to develop delirium after surgery. Discussion: Patients undergoing intervention by the OT team did not have a lower incidence of POD compared to the group treated only with standard non-pharmacological measures in adults older than 75 years who went for major surgery. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT03704090.

Pendelluft in hypoxemic patients resuming spontaneous breathing: proportional modes versus pressure support ventilation.

BACKGROUND: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS). METHODS: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔPes 100 ms]) and inspiratory effort (as the esophageal pressure-time product per minute [PTPmin]). We performed repeated measures analysis with post-hoc tests and mixed-effects models. RESULTS: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔPes 100 ms of -2.8 [-3.8--1.9] cm H2O, -3.6 [-3.9--2.4] cm H2O and -2.1 [-2.5--1.1] cm H2O, respectively, p < 0.001 for both comparisons; PTPmin of 155 [118-209] cm H2O s/min, 197 [145-269] cm H2O s/min, and 134 [93-169] cm H2O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (ß = -2.771, p-value < 0.001) and inspiratory effort (ß = 0.026, p < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTPmin (ß = 2.606, p = 0.010 for NAVA, and ß = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (ß = 2.643, p = 0.009 for PAV +). CONCLUSIONS: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV.