LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis.

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.

Automatic tube compensation for liberation from prolonged mechanical ventilation in tracheostomized patients: A retrospective analysis.

BACKGROUND: To analyze the predictability of an automatic tube compensation (ATC) screening test compared with the conventional direct liberation test performed before continuous oxygen support for MV liberation. METHODS: This retrospective study analyzed tracheostomized patients with prolonged MV in a weaning unit of a medical center in Taiwan. In March 2020, a four-day ATC test to screen patient eligibility for ventilator liberation was implemented, intended to replace the direct liberation test. We compared the predictive accuracy of these two screening methods on the relevant outcomes in the two years before and one year after the implementation of this policy. RESULTS: Of the 403 cases, 246 (61%) and 157 (39%) received direct liberation and ATC screening tests, respectively. These two groups had similar outcomes: successful weaning upon leaving the Respiratory Care Center (RCC), success on day 100 of MV, success at hospital discharge, and in-hospital survival. Receiver operating characteristic curve analysis showed that the ATC screening test had better predictive ability than the direct liberation test for RCC weaning, discharge weaning, 100-day weaning, and in-hospital survival. CONCLUSION: This closed-circuit ATC screening test before ventilator liberation is a feasible and valuable method for screening PMV patients undergoing ventilator liberation in the pandemic era. Its predictability for a comparison with the open-circuit oxygen test requires further investigation.

Safety and efficacy of vacuum bottle plus catheter for drainage of iatrogenic pneumothorax.

BACKGROUND: Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed. METHODS: Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded. RESULTS: From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than - 20 cmH2O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2-569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1-4 days vs 3-7 days], p < .05). Vacuum bottle assisted air drainage also help identifying patients with persistent pneumothorax and necessitate the subsequent management. The event-free duration of persistent air leak in the intervention group was also comparable with that of conservative treatment (5 days vs 5 days [interquartile range 5-8 days vs 3-7 days], p = .45). CONCLUSIONS: Vacuum bottle plus catheter drainage of iatrogenic pneumothorax is a safe and efficient procedure. It may be considered as an alternative management of stable post-procedural pneumothorax with size larger than 15%. Trial registration The study protocol was approved by the Research Ethics Committee of National Taiwan University Hospital (No. 201805105DINA) on 6th August, 2018. The first participant was enrolled on 23rd August, 2018 after Research Ethics Committee approval. This clinical trial complete registration at U.S. National Library of Medicine clinicaltrials.gov with identifier NCT03724721 and URL: https://clinicaltrials.gov/ct2/show/NCT03724721 on 30th October, 2018.

The application of ultrasound shear wave elastography in the prediction of paradoxical upgrading reaction in tuberculous lymphadenitis. a pilot study.

BACKGROUND: Paradoxical upgrading reaction (PUR) indicates the unanticipated deterioration during therapy in patients with tuberculous lymphadenitis. We investigated the diagnostic performance of the ultrasonography and shear wave elastography (SWE) in predicting the therapeutic response of peripheral tuberculous lymphadenitis. METHODS: A prospective observational study was conducted from December 2017 to August 2020. Participants diagnosed with peripheral tuberculous lymphadenitis were included for a longitudinal follow-up utilizing ultrasonography with two-dimensional SWE to record sonographic features and the maximum elasticity value (Emax). We defined PUR as the development of any worsening symptoms of the pre-existing lymphadenitis within one month after the previous ultrasonography. RESULTS: A total of 108 sonographic and SWE examinations were performed in 20 enrollees (75% woman), and their mean ( ± standard deviation) age was 49.6 ( ± 22.7) years. The area under the receiver operating characteristic curve of Emax to predict the next-month PUR was 0.906 at the cut-point of 85 kPa, with an accuracy of 87.0%, a sensitivity of 81.1% and a specificity of 87.9%. Multivariate analysis indicated that Emax > 85 kPa (OR: 24.85, 95% CI: 4.01-154.08, p < 0.001), Emax increment rate >2 kPa/month (OR: 15.14, 95% CI: 4.24-54.06, p < 0.001), and heterogeneous echogenicity (OR: 4.37, 95% CI: 1.16-16.43, p = 0.029) were independent sonographic predictors for PUR in the coming month. CONCLUSION: A high and non-declining Emax level and heterogeneous echogenicity were associated with the next-month PUR of tuberculous lymphadenitis. Ultrasonography with SWE may be a potential radiologic marker to predict the therapeutic response of tuberculous lymphadenitis.

Application of transthoracic shear-wave ultrasound elastography in lung lesions.

INTRODUCTION: Tissue stiffness information may help in the diagnosis of lung lesions. This study aimed to investigate and validate the application of transthoracic two-dimensional shear-wave ultrasound elastography in differentiating malignant from benign subpleural lung lesions. METHODS: This study involved one retrospective observational derivation cohort from January 2016 to December 2017 and one prospective observational validation cohort from December 2017 to December 2019. The inclusion criterion was radiographic evidence of pulmonary lesions. The patients were categorised into air bronchogram and hypoechoic groups based on B-mode grayscale images. The elasticity of subpleural lung lesions with acceptable shear-wave propagation was measured. Diagnoses were made on the basis of pathology, microbiological studies or following up the clinical course for at least 6 months. RESULTS: A total of 354 patients were included. Among the 121 patients in the derivation cohort, a receiver operating characteristic curve was constructed and the cut-off point to differentiate benign from malignant lesions was 65 kPa with a Youden index of 0.60 and an accuracy of 84.3%. Among the 233 patients in the validation cohort, the diagnostic performance was maintained, with a Youden index of 0.65 and an accuracy of 86.7%. Upon applying the cut-off point to the air bronchogram group, the Youden index was 0.70 and the accuracy was 85.0%. CONCLUSIONS: This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. METHODS: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. RESULTS: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia. CONCLUSION: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Changes in albuminuria during the spontaneous breathing trial: A prospective observational study.

BACKGROUND: We hypothesized urine albumin concentration may detect the early increasing cardiac load during the spontaneous breathing trial (SBT). The purpose of our study is to determine whether the changes in urine albumin concentration before and after the SBT correlate with SBT outcome. METHODS: This prospective observational study was conducted from January 2013 to September 2013. Patients receiving endotracheal tube intubation due to acute respiratory failure were included. Urine albumin concentration was measured upon admission to the intensive care unit, before and after the SBT. RESULTS: A total of 211 patients with respiratory failure were screened. Finally, 69 patients were included for analysis. Among the 69 patients received the SBT, 61 patients passed the SBT while 8 patients didn't. Urine albumin concentration upon admission was 251.00 ± 108.21 mg/g in the SBT success group and 260.87 ± 77.95 mg/g in the SBT failure group (p = 0.97). The mean percent change in urine albumin concentration during the SBT was significantly higher in the SBT failure group (+58.44%) than in the SBT success group (+13.11%) (p = 0.02). Univariable and multivariable logistic regression model showed that the difference of urine albumin concentration before and after the SBT correlated significantly with SBT failure (adjusted OR:1.04, p = 0.01). CONCLUSION: This open label pilot study demonstrates the significant association of the changes in urine albumin concentration with SBT outcome. Further study is warranted to investigate the predictive value of urine albumin concentration.

Weaning outcome of solid cancer patients requiring mechanical ventilation in the intensive care unit.

BACKGROUND: Whether the weaning outcome of solid cancer patients receiving mechanical ventilation (MV) in the intensive care unit (ICU) is comparable to that in non-cancer patients is unknown. The aim of this study was to compare the weaning outcomes between non-cancer patients and patients with different types of cancer. METHODS: We studied patients requiring MV during ICU stay for medical reasons between 2012 and 2014. Cancer patients were grouped into those with lung cancer (LC), head and neck cancer (HNC), hepatocellular carcinoma (HCC), and other cancers (OC). The primary endpoint was successful weaning at day 90 after the initiation of MV, and the main secondary endpoints were 28-day and 90-day mortality after ICU admission. RESULTS: Five hundred and eighteen patients with solid cancers and 1362 non-cancer patients were recruited. The rate of successful weaning at day 90 was 57.9% in cancer patients, which was lower than 68.9% in non-cancer patients (p < 0.001). Compared to non-cancer patients, LC was associated with a lower probability of weaning at day 90 (hazard ratio 0.565, 95% CI 0.446 to 0.715), while HNC, HCC, and OC had similar probabilities. The 28-day and 90-day mortality rates were higher in cancer patients than in non-cancer patients (45.2% vs. 29.4%, and 65.6% vs. 37.7%, respectively, both p < 0.001). CONCLUSION: Among mechanically ventilated patients in the ICU, those with LC were associated with a lower probability of weaning at day 90 compared to non-cancer patients.

Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study.

BACKGROUND: Inhaled nitric oxide (iNO) is a rescue therapy for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS). Pooled data from clinical trials have signaled a renal safety warning for iNO therapy, but the significance of these findings in daily clinical practice is unclear. We used primary data to evaluate the risk of iNO-associated renal dysfunction in patients with ARDS. METHODS: We conducted a cohort study using data from a tertiary teaching hospital to evaluate the risk of incident renal replacement therapy (RRT) in iNO users compared with that of non-users. Propensity score matching and competing-risks regression were used for data analysis. Residual confounding was assessed by means of a rule-out approach. We also evaluated effect modification by pre-specified factors using stratified analysis. RESULTS: We identified 547 patients with ARDS, including 216 iNO users and 331 non-users. At study entry, 313 (57.2%) patients had moderate ARDS and 234 (42.8%) had severe ARDS. The mean patient age was 63 ± 17 years. The crude hazard ratio of the need for RRT in iNO users compared with non-users was 2.23 (95% CI, 1.61-3.09, p < 0.001). After propensity score matching, there were 151 iNO users matched to 151 non-users. The adjusted hazard ratio was 1.59 (95% CI, 1.08-2.34, p = 0.02). In the stratified analysis, we found that older aged patients (≥65 years) were more susceptible to iNO-associated kidney injury than younger patients (p = 0.05). CONCLUSIONS: This study showed that iNO substantially increased the risk of renal dysfunction in patients with ARDS. Older aged patients were especially susceptible to this adverse event.

Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Inhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS. METHODS: A systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model. RESULTS: Ten RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75). CONCLUSIONS: The available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.

Acute Respiratory Distress Syndrome in Patients Discharged From a Tertiary Hospital in Taiwan: Long-Term Survival and Prognostic Factors.

BACKGROUND: Acute respiratory distress syndrome (ARDS) carries significant morbidity and mortality. No previous studies have investigated the long-term outcomes of ARDS patients in Taiwan. OBJECTIVE: This study aimed to investigate the survival of ARDS patients after discharge from the hospital in Taiwan. METHODS: Medical records from 150 ARDS patients discharged alive from the intensive care unit from January 2004 to June 2009 were reviewed. Survival of these patients was followed for 5 years, and prognostic factors were identified. RESULTS: Cumulative survival rates were 81.4% at 6 months, 79.0% at 1 year, 67.2% at 2 years, and 45.7% at 5 years. Independent prognostic factors influencing both 1- and 5-year survival rates were age, previous lung disease, and disposition after discharge. For 5-year survival, renal disease was also an independent risk factor. DISCUSSION: The mortality rate of ARDS survivors after intensive care unit discharge is still high in Taiwan. Three independent risk factors were found to affect the overall survival of these patients.

Application of heart-rate variability in patients undergoing weaning from mechanical ventilation.

INTRODUCTION: The process of weaning may impose cardiopulmonary stress on ventilated patients. Heart-rate variability (HRV), a noninvasive tool to characterize autonomic function and cardiorespiratory interaction, may be a promising modality to assess patient capability during the weaning process. We aimed to evaluate the association between HRV change and weaning outcomes in critically ill patients. METHODS: This study included 101 consecutive patients recovering from acute respiratory failure. Frequency-domain analysis, including very low frequency, low frequency, high frequency, and total power of HRV was assessed during a 1-hour spontaneous breathing trial (SBT) through a T-piece and after extubation after successful SBT. RESULTS: Of 101 patients, 24 (24%) had SBT failure, and HRV analysis in these patients showed a significant decrease in total power (P = 0.003); 77 patients passed SBT and were extubated, but 13 (17%) of them required reintubation within 72 hours. In successfully extubated patients, very low frequency and total power from SBT to postextubation significantly increased (P = 0.003 and P = 0.004, respectively). Instead, patients with extubation failure were unable to increase HRV after extubation. CONCLUSIONS: HRV responses differ between patients with different weaning outcomes. Measuring HRV change during the weaning process may help clinicians to predict weaning results and, in the end, to improve patient care and outcome.

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis.

INTRODUCTION: The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model. RESULTS: Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, -0.28; 95% confidence interval (CI), -0.53 to -0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, -0.01; 95% CI, -0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27). CONCLUSIONS: The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.

Assessing breathing effort by barometric whole-body plethysmography and its relationship with prognosis in client-owned cats with respiratory distress.

BACKGROUND: Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated. HYPOTHESIS: Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival. ANIMALS: Fifty-two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014. METHODS: This is a prospective observational study. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole-body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow-up data, including disease category, clinical outcomes, and survival, were prospectively collected. RESULTS: Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158-1240) than normal cats (269 mL/kg; range, 168-389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher-than-normal MV/BW trends. A cutoff value of 373 mL/kg (1.4-fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.02-1.35; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress.

Quantifiable features of a tidal breathing phenotype in dogs with severe bronchomalacia diagnosed by bronchoscopy.

Dynamic lower airway obstruction is the primary component of canine bronchomalacia, but the ventilatory function remains underinvestigated. This prospective study analyzed tidal breathing characteristics in 28 dogs, comprising 14 with severe bronchomalacia diagnosed by bronchoscopy versus 14 without respiratory disease. Spirometry was conducted in all dogs. Bronchoscopy with bronchoalveolar lavage or brush under anesthesia was performed in 14 dogs with cough and expiratory effort. Severe bronchomalacia was defined by the severity of collapse and total number of bronchi affected. Ventilatory characteristics were compared between groups. Results revealed that dogs with severe bronchomalacia had lower minute volume (218 vs 338 mL/kg, p = .039) and greater expiratory-to-inspiratory time ratio (1.55 vs 1.35, p = .01) compared to control dogs. The tidal breathing pattern of dogs with bronchomalacia was different from that of normal dogs, and the pattern differed from the concave or flat expiratory curves typical of lower airway obstruction. Compared to control dogs, dogs with severe bronchomalacia had a significantly prolonged low-flow expiratory phase (p < .001) on the flow-time plot and a more exponential shape of the expiratory curve (p < .001) on the volume-time plot. Flow-time index ExpLF/Te (>0.14) and volume-time index Vt-AUCexp (≤31%) had a high ROC-AUC (1.00, 95% confidence interval 0.88 to 1.00) in predicting severe bronchomalacia. In conclusion, the tidal breathing pattern identified here indicates abnormal and complicated ventilatory mechanics in dogs with severe bronchomalacia. The role of this pulmonary functional phenotype should be investigated for disease progression and therapeutic monitoring in canine bronchomalacia.

Influence of concurrent lower respiratory tract disease on point-of-care lung ultrasound in small-breed dogs with myxomatous mitral valve disease.

BACKGROUND: Small-breed dogs commonly have concurrent myxomatous mitral valve disease (MMVD) and lower respiratory tract disease (LRTD). HYPOTHESIS: Small-breed dogs with preclinical MMVD and concurrent LRTD have more B-lines on point-of-care lung ultrasound (POC-LUS) compared to dogs without concurrent LRTD and are prone to misdiagnose as cardiogenic pulmonary edema (CPE). ANIMALS: A total of 114 small-breed dogs with preclinical MMVD. METHODS: A prospective study was conducted, in which POC-LUS was obtained and the number of B-lines was calculated by a single clinician using the Veterinary Bedside Lung Ultrasound Examination protocol. The presence/absence of LRTD was assessed by clinicians blinded to the POC-LUS results. RESULTS: Fifty and 64 dogs were in ACVIM stage B1 and B2, respectively. The presence of LRTD was prevalent in 74.6% (85/114) of small-breed dogs with preclinical MMVD. When a previously reported criterion for CPE diagnosis (≥2 sites with >3 B-lines/site) was applied, false-positive results were observed in 15.8% (18/114) of dogs with preclinical MMVD. The summated number of B-lines (3 vs. 1, P = .003), as well as the false-positive rate (20% vs 3%, P = .04), were significantly higher in dogs with LRTD compared with dogs without LRTD. Multivariable logistic regression showed the presence of abnormalities other than B-line on POC-LUS (eg, thickened pleura or consolidation) could predict false-positive results (odds ratio = 3.75, 95% confidence intervals 1.12-12.54; P = .03) after adjustment for other clinical and echocardiographic factors. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent LRTD and abnormalities other than B-lines should be considered in the interpretation of POC-LUS in MMVD dogs.

Impact of ventilator settings during venovenous extracorporeal membrane oxygenation on clinical outcomes in influenza-associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown. Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes. Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs. 12 breaths/min, p = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p = 0.034). Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population.

Physical training is beneficial to functional status and survival in patients with prolonged mechanical ventilation.

BACKGROUND/PURPOSE: Early physical training is necessary for severely deconditioned patients undergoing prolonged mechanical ventilation (PMV), because survivors often experience prolonged recovery. Long-term outcomes after physical training have not been measured; therefore, we investigated outcome during a 1-year period after physical training for the PMV patients. METHODS: We conducted a prospective randomized control trial in a respiratory care center. Thirty-four patients were randomly assigned to the rehabilitation group (n = 18) and the control group (n = 16). The rehabilitation group participated in supervised physical therapy training for 6 weeks, and continued in an unsupervised maintenance program for 6 more weeks. The functional independence measurement (FIM) was used to assess functional status. Survival status during the year after enrollment, the number of survivors discharged, and the number free from ventilator support were collected. These outcome parameters were assessed at entry, immediately after the 6 weeks physical therapy training period, after 6 weeks unsupervised maintenance exercise program, and 6 months and 12 months after study entry. RESULTS: The scores of total FIM, motor domain, cognitive domain, and some sub-items, except for the walking/wheelchair sub-item, increased significantly in the rehabilitation group at 6 months postenrollment, but remained unchanged for the control group. The eating, comprehension, expression, and social interaction subscales reached the 7-point complete independence level at 6 months in the rehabilitation group, but not in the control group. The 1-year survival rate for the rehabilitation group was 70%, which was significantly higher than that for the control group (25%), although the proportion of patients discharged and who were ventilator-free in the rehabilitation and control groups did not differ significantly. CONCLUSION: Six weeks physical therapy training plus 6 weeks unsupervised maintenance exercise enhanced functional levels and increased survival for the PMV patients compared with those with no such intervention. Early physical therapy interventions are needed for the PMV patients in respiratory care centers.