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.

Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells.

The field cancerization effect has been proposed to explain bladder cancer's multifocal and recurrent nature, yet the mechanisms of this effect remain unknown. In this work, using cell biology, flow cytometry, and qPCR analyses, along with a xenograft mouse tumor model, we show that chronic exposure to tumor-derived extracellular vesicles (TEVs) results in the neoplastic transformation of nonmalignant human SV-HUC urothelial cells. Inhibition of EV uptake prevented this transformation. Transformed cells not only possessed several oncogenic properties, such as increased genome instability, loss of cell-cell contact inhibition, and invasiveness, but also displayed altered morphology and cell structures, such as an enlarged cytoplasm with disrupted endoplasmic reticulum (ER) alignment and the accumulation of smaller mitochondria. Exposure of SV-HUC cells to TEVs provoked the unfolded protein response in the endoplasmic reticulum (UPRER). Prolonged induction of UPRER signaling activated the survival branch of the UPRER pathway, in which cells had elevated expression of inositol-requiring enzyme 1 (IRE1), NF-κB, and the inflammatory cytokine leptin, and incurred loss of the pro-apoptotic protein C/EBP homologous protein (CHOP). More importantly, inhibition of ER stress by docosahexaenoic acid prevented TEV-induced transformation. We propose that TEVs promote malignant transformation of predisposed cells by inhibiting pro-apoptotic signals and activating tumor-promoting ER stress-induced unfolded protein response and inflammation. This study provides detailed insight into the mechanisms underlying the bladder cancer field effect and tumor recurrence.

Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

PURPOSE: High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. MATERIALS AND METHODS: Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. RESULTS: Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. CONCLUSIONS: Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies.

E-liquid exposure induces bladder cancer cells to release extracellular vesicles that promote non-malignant urothelial cell transformation.

The vaping of electronic cigarettes (E-cigarettes) has recently emerged as a popular alternative to traditional cigarette smoking, but its association with bladder cancer (BC) risk remains to be established. BC patients exhibit high rates of recurrent disease, possibly as a consequence of the field cancerization effect. We have shown that BC-derived extracellular vesicles (BCEVs) can permanently alter recipient urothelial cells in predisposed fields such that they become fully transformed malignant cells. To model the role that BCEVs may play in this potentially oncogenic setting, we treated TCCSUP BC cells with cigarette smoke extract, unflavored E-liquid, or menthol flavored E-liquid. Those treated BCEVs were then tested for their tumorigenic potential. We found that these smoking- and E-cigarette-related BCEVs were able to promote oxidative stress, inflammatory signaling, and DNA damage in recipient SV-HUC urothelial cells. Strikingly, menthol E-liquid-induced BCEVs significantly increased rates of malignant urothelial cell transformation. While further in vivo validation of the simultaneous effects of E-liquid and E-liquid-induced BCEVs on field cancerization is needed, these data highlight the possibility that E-cigarettes may compound user risk in a manner that can contribute to higher rates of BC incidence or recurrence.

Treatment of electronic cigarette or vaping product use-associated lung injury (EVALI) by corticosteroid and low-dose pirfenidone: Report of a case.

Electronic (e)-cigarette or vaping product use-associated lung injury (EVALI) is a novel and potentially lethal disease first reported in the United States. We report the case of a 56-year-old man who presented to our hospital with dyspnoea and cough lasting for 2 months after using an e-cigarette for approximately 50 puffs over 2 weeks. Physical examination revealed crackles in the left lower lung. High-resolution computed tomography (HRCT) showed consolidation and ground-glass opacities in both lungs. The baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were 65.7% and 63.9% of the predicted, respectively. Lung biopsy revealed organizing pneumonia with focal fibrosis. In addition to prednisolone, he was treated with a low-dose pirfenidone (200 mg three times per day) due to the persistence of a mild cough, exertional dyspnoea and basal crackles after discharge. His symptoms and FVC significantly improved, but the recovery of the DLCO was slow. The follow-up HRCT demonstrated only minimal fibrotic changes. To our knowledge, this was the first reported case of EVALI successfully treated with a combination of corticosteroid and antifibrotic agents.

Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with high mortality, and heterogeneity in MIBC results in variable clinical outcomes, posing challenges for clinical management. Extracellular vesicles (EVs) derived from MIBC have been shown to promote cancer progression. EVs derived from bladder cell lines were subjected to proteomic analysis, and periostin was chosen for further characterization due to its stage-specific gene expression profile. Knockdown of periostin by RNA interference reduces invasiveness in vitro and produces a rounder morphology. Importantly, treating low grade BC cells with periostin-rich EVs promotes cell aggressiveness and activates ERK oncogenic signals, and periostin suppression reverses these effects. These data suggest that MIBC might transfer periostin in an EV-mediated paracrine manner to promote the disease. To determine the potential of periostin as a bladder cancer indicator, patient urinary EVs were examined and found to have markedly higher levels of periostin than controls. In addition, immunohistochemical staining of a bladder cancer tissue microarray revealed that the presence of periostin in MIBC cells is correlated with worse prognosis. In conclusion, periostin is a component of bladder cancer cells associated with poor clinical outcome, and EVs can transfer oncogenic molecules such as periostin to affect the tumor environment and promote cancer progression.