Physiological Effects of High-Flow Tracheal Oxygen in Tracheostomized Patients Weaning From Mechanical Ventilation.

BACKGROUND: High-flow tracheal oxygen (HFTO) is being used as supportive therapy during weaning in tracheostomized patients difficult to wean from invasive mechanical ventilation. There is, however, no clinical evidence for such a strategy. Therefore, we conducted a systematic review to summarize studies evaluating the physiologic effects of HFTO during tracheostomy-facilitated weaning and to identify potential areas for future research in this field. METHODS: Observational and interventional studies on critically ill subjects weaning from mechanical ventilation via tracheostomy published until December 22, 2022, were eligible. Studies on high-flow oxygen, only in children, non-human models or animals, on clinical outcome only, abstracts without full-text availability, case reports, and reviews were excluded. Main outcomes were end-expiratory lung volume (EELV) and tidal volume using electrical impedance tomography, respiratory effort assessed by esophageal manometry, work of breathing and neuroventilatory drive as assessed by electrical activity of the diaphragm (EAdi) signal, airway pressure (Paw), oxygenation (PaO2 /FIO2 or SpO2 /FIO2 ), breathing frequency, tidal volume, and PaCO2 . RESULTS: In total, 1,327 references were identified, of which 5 were included. In all studies, HFTO was administered with flow 50 L/min and compared to conventional O2 therapy in a crossover design. The total average duration of invasive ventilation at time of measurements ranged from 11-27 d. In two studies, PaO2 /FIO2 and mean Paw were higher with HFTO. EELV, tidal volumes, esophageal pressure swings, and EAdi were similar during high-flow tracheal oxygen and conventional O2 therapy. CONCLUSIONS: The main physiological effect of HFTO as compared to conventional O2 therapy in tracheostomized subjects weaning from mechanical ventilation was improved oxygenation that is probably flow-dependent. Respiratory effort, lung aeration, neuroventilatory drive, and ventilation were similar for HFTO and conventional O2 therapy. Future studies on HFTO should be performed early in the weaning process and should evaluate its effect on sputum clearance and patient-centered outcomes like dyspnea.

Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19.

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort ( n = 214 patients) was 53% and 60% in ward and ICU starters, respectively ( p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pa o2 :F io2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.

Diaphragm excursions as proxy for tidal volume during spontaneous breathing in invasively ventilated ICU patients.

There is a need to monitor tidal volume in critically ill patients with acute respiratory failure, given its relation with adverse clinical outcome. However, quantification of tidal volume in non-intubated patients is challenging. In this proof-of-concept study, we evaluated whether ultrasound measurements of diaphragm excursion could be a valid surrogate for tidal volume in patients with respiratory failure. Diaphragm excursions and tidal volumes were simultaneously measured in invasively ventilated patients (N = 21) and healthy volunteers (N = 20). Linear mixed models were used to estimate the ratio between tidal volume and diaphragm excursion. The tidal volume-diaphragm excursion ratio was 201 mL/cm in ICU patients [95% confidence interval (CI) 161-240 mL/cm], and 361 (294-428) mL/cm in healthy volunteers. An excellent association was shown within participants (R2 = 0.96 in ICU patients, R2 = 0.90 in healthy volunteers). However, the differences between observed tidal volume and tidal volume as predicted by the linear mixed models were considerable: the 95% limits of agreement in Bland-Altman plots were ± 91 mL in ICU patients and ± 396 mL in healthy volunteers. Likewise, the variability in tidal volume estimation between participants was large. This study shows that diaphragm excursions measured with ultrasound correlate with tidal volume, yet quantification of absolute tidal volume from diaphragm excursion is unreliable.

Antibodies against angiotensin II receptor type 1 and endothelin A receptor are increased in COVID-19 patients.

Background: Increased titers of autoantibodies targeting the G-protein-coupled receptors angiotensin II type 1 receptor (AT1R) and endotelin-1 type A receptor (ETAR) are associated with severe coronavirus disease 2019 (COVID-19) infection. The aim of this study was to determine whether 1) these antibodies are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness, 2) if they are formed during illness, and 3) if they correlate with inflammatory markers or long-term symptoms. Methods: Antibodies against AT1R, ETAR, and antinuclear antibodies (ANAs) were measured in n=40 prospectively enrolled COVID-19 patients and n=207 COVID-19 patients included in a biobank. Clinical and laboratory findings were prospectively and retrospectively assessed in both cohorts, and results were combined for analysis. The presence of auto-antibodies against AT1R or ETAR in peripheral blood was compared between hospitalized patients with COVID-19 and controls (n=39). Additionally, AT1R and ETAR titers were compared between patients with an unfavorable disease course, defined as intensive care admission and/or death during hospital admission (n=121), to those with a favorable disease course (n=126). A subset of intubated patients with severe COVID-19 were compared to intubated patients with acute respiratory distress syndrome (ARDS) due to any other cause. Results: Significantly increased AT1R and ETAR antibody titers were found in COVID-19 patients compared to controls, while titers were equal between favorable and unfavorable COVID-19 disease course groups. On ICU, intubated patients with COVID-19 had significantly increased AT1R and ETAR titers compared to patients with ARDS due to any other cause. The titers did not correlate with baseline inflammatory markers during admission or with diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up. Conclusions: In patients hospitalized for COVID-19, antibodies against AT1R and ETAR are increased compared to controls and patients with ARDS due to other causes than COVID-19. The baseline antibody titers do not correlate with inflammatory markers or long-term symptoms in this study.

Airborne virus shedding of the alpha, delta, omicron SARS-CoV-2 variants and influenza virus in hospitalized patients.

Airborne transmission is an important transmission route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological data indicate that certain SARS-CoV-2 variants, like the omicron variant, are associated with higher transmissibility. We compared virus detection in air samples between hospitalized patients infected with different SARS-CoV-2 variants or influenza virus. The study was performed during three separate time periods in which subsequently the alpha, delta, and omicron SARS-CoV-2 variants were predominant. In total, 79 patients with coronavirus disease 2019 (COVID-19) and 22 patients with influenza A virus infection were included. Collected air samples were positive in 55% of patients infected with the omicron variant in comparison to 15% of those infected with the delta variant (p < 0.01). In multivariable analysis, the SARS-CoV-2 omicron BA.1/BA.2 variant (as compared to the delta variant) and the viral load in nasopharynx were both independently associated with air sample positivity, but the alpha variant and COVID-19 vaccination were not. The proportion of positive air samples patients infected with the influenza A virus was 18%. In conclusion, the higher air sample positivity rate of the omicron variant compared to previous SARS-CoV-2 variants may partially explain the higher transmission rates seen in epidemiological trends.

Analyses of abdominal adiposity and metabolic syndrome as risk factors for respiratory distress in COVID-19.

BACKGROUND: Several characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19. METHODS: A prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity-assessed by an increased waist-hip ratio-and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses. RESULTS: In total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014). CONCLUSION: This study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference. TRIAL REGISTRATION NUMBER: NL8580.

Pneumothorax in patients with prior or current COVID-19 pneumonia.

As the number of COVID-19 cases emerge, new complications associated with the disease are recognized. We present three cases of spontaneous pneumothorax in patients with COVID-19. They show that a pneumothorax can occur during different phases of disease, in patients without a pulmonary disease history and is not necessarily associated to positive pressure ventilation or severity of COVID-19. Although the exact causative mechanisms remain unknown, this observation might imply that extensive alveolar destruction due to COVID-19 may lead to bulla formation resulting in subsequent pneumothorax.

Wnt targets genes are not differentially expressed in desmoid tumors bearing different activating ß-catenin mutations.

INTRODUCTION: Sporadic desmoid-type fibromatosis (DTF) is a rare soft tissue tumor of mesenchymal origin. It is characterized by local invasive growth and unpredictable growth behavior. Three distinct mutations involving the CTNNB1 (ß-catenin) gene have been identified in the vast majority of DTF tumors, which cause activation of the Wnt signaling pathway and impact prognosis. This study examines whether the different CTNNB1 mutants (T41A, S45F) occurring in DTF tumors differentially affect Wnt signaling activity, which might explain the different disease course between DTF patients harboring different CTNNB1 mutations. MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR) on 61 formalin fixed paraffin embedded DTF samples with known CTNNB1 status was used to measure the relative mRNA expression level of Wnt target genes AXIN2, DKK1 and CCND1. Additionally, publicly available mRNA expression data retrieved from the Gene Expression Omnibus of 128 DTF samples were used for an unsupervised cluster analyses based on the expression of a selection of Wnt targets. RESULTS: No statistically significant difference in relative expression levels of Wnt target genes AXIN2, DKK1 and CCND1 was identified between either CTNNB1 wild-type, S45F or T41A mutated DTF samples. Moreover, the hierarchical cluster analyses using selected Wnt targets did not discriminate between different CTNNB1 mutation types. CONCLUSIONS: No differences in the expression levels of Wnt target genes were observed between the different CTNNB1 mutation types in DTF tumors. Further studies are needed to decipher the mechanism accounting for the diverse disease courses between DTF patients with different CTNNB1 variants.