Changes in tidal breathing biomarkers as indicators of treatment response in AECOPD patients in an acute care setting.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a complication of COPD that typically necessitates intensified treatment and hospitalization. It is linked to higher morbidity, mortality and healthcare spending. Assessment of therapy response for AECOPD is difficult due to the variability of symptoms and limitations in current measures. Hence, there is a need for new biomarkers to aid in the management of AECOPD in acute care settings. MATERIALS AND METHODS: Fifteen hospitalized AECOPD patients (GOLD 3-4) were enrolled in this study. Treatment response was assessed daily through clinical evaluations and by monitoring tidal breathing biomarkers (respiratory rate [RR], expiratory time [Tex], inspiratory time [Tin], expiratory pause [Trst], total breath time [Ttot]), using a novel, wearable nanosensor-based device (SenseGuard™). RESULTS: Patients who showed significant clinical improvement had substantial changes in ΔTex/Ttot (+14%), ΔTrst/Ttot (-18%), and ΔTin/Tex (+0.09), whereas patients who showed mild or no clinical improvement had smaller changes (+5%, +3%, and -0.03, respectively). Linear regression between change in physician's assessment score and the median change in tidal breathing parameters was significant for Tin/Tex (R2 â€‹= â€‹0.449, ∗p â€‹= â€‹0.017), Tex/Ttot (R2 â€‹= â€‹0.556, ∗p â€‹= â€‹0.005) and Trst/Ttot (R2 â€‹= â€‹0.446, ∗p â€‹= â€‹0.018), while no significant regression was observed for RR, Tin/(Trst â€‹+ â€‹Tex) and Tin/Ttot. CONCLUSIONS: Our study demonstrates the potential of the SenseGuard™ to monitor treatment response in AECOPD patients by measuring changes in tidal breathing biomarkers, which were shown to be associated with significant changes in the patients' respiratory condition as evaluated by physicians. However, further large-scale clinical studies are needed to confirm these findings.

Transbronchial cryobiopsy in unexplained, severe ARDS: a single center retrospective case series.

BACKGROUND: Acute respiratory distress syndrome (ARDS) deptics an acute form of lung infjury with often severe respiratory impairment that requires invasive mechanical ventilation. Since ARDS can be caused by several distinct etiologies, correct characterization is desired and frequently challenging. Surgical lung biopsy was previously reported to be of additive value. We describe our institutional experience using transbronchial cryobiopsy (TBCB) for further characterization of severe and unexplained ARDS cases. CASE PRESENTATION: We retrospectively collected data of TBCB in patients with unexplained ARDS, whether with or without ECMO-support. Between 2019 and 2020 TBCB was performed in eight patients. Decision for the intervention was decided in multidisciplinary discussion. Five patients were treated with ECMO. The median duration of invasive ventilation before TBCB was 24 days. TBCB was performed in one segment, that was prophylactically occluded by Watanabe spigot or swab after the procedure. Histology results and their contribution to further therapeutic decisions were analyzed. Histology revealed five diffuses alveolar damage, one acute fibrinoid organizing pneumonia, one cryptogenic organizing pneumonia and one lung cancer. All results contributed to the decision of further management. While no pneumothorax or severe endobronchial bleeding occurred, two delayed hematothoraces needed surgical treatment. No patients died due to TBCB. CONCLUSION: TBCB is feasible in ARDS even during ECMO treatment. Histologic results can play a significant role in therapeutic and ethic discussion to guide the patients' care. Side effects should be considered and monitored.

Crown-Cut Endobronchial Ultrasound Guided Transbronchial Aspiration Needle: First Real-World Experiences.

Advancements in personalized medicine have increased the demand for quantity and preservation of tissue architecture of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples. These demands may be addressed by the SonoTip TopGain® needle, which has a 3-point crown-cut design that contrasts with the standard single bevel design of the ViziShot 2®. The objective was to compare the SonoTip TopGain® and ViziShot 2® needles by considering biopsy sample characteristics, diagnostic accuracy, and patient safety. The primary endpoint of the study was the number of high-power fields (HPFs) in the center of the formalin-fixed paraffin-embedded cell block per sample. The lymph node with the highest probability for malignant infiltration based on size and sonographic appearance was chosen as the target lymph node for 20 patients. The same lymph node in each patient was sampled using both the ViziShot 2® and SonoTip TopGain® needles. The samples were measured, sliced, and analyzed by a pathologist. Sixteen patients were biopsied with both needles. Four patients could not be biopsied with the SonoTip TopGain® needle since it could not penetrate cartilage or be repositioned to bypass cartilage. HPFs and sample dimensions were significantly greater in the patients where sampling with the SonoTip TopGain® needle was possible (p = 0.007 and p = 0.005, respectively). Diagnostic accuracy and safety profiles were comparable. Significantly more material can be sampled using the SonoTip TopGain® needle when cartilage penetration can be avoided. This improves the yield for molecular workup in the era of personalized medicine.

Liquid biopsy - Performance of the PAXgene® Blood ccfDNA Tubes for the isolation and characterization of cell-free plasma DNA from tumor patients.

BACKGROUND: In most research laboratories the use of EDTA tubes for the isolation of plasma DNA from tumor patients is standard. Unfortunately these tubes do not allow for an extended storage of samples before processing and prevent EDTA tubes from being shipped at ambient temperature. The aim of our study was to compare the quantity and quality of plasma DNA isolated from EDTA and PAXgene® Blood ccfDNA Tubes in different downstream applications. METHODS: We enrolled 29 patients in our study. Blood samples were drawn into EDTA and PAXgene® Blood ccfDNA Tubes and were processed on day 0 and day 7 after storage at ambient temperature. The plasma DNA from 10 patients was isolated manually. For the DNA isolation from the plasma of 19 additional patients we used the automated QIAsymphony system. The total amount DNA from all samples was measured with a quantitative real-time PCR assay. In addition the amount of methylated mSHOX2 plasma DNA was determined. RESULTS: While the 7day storage lead to an increased amount of total DNA in almost all EDTA tubes, this effect was only seen in very few PAXgene® Blood ccfDNA Tubes. The stabilization solution which prevents the lysis of blood cells had no effect on the method for quantification of methylated sequences in these samples. CONCLUSION: The quantity and quality of plasma DNA from both types of blood draw tubes are comparable. DNA from PAXgene® Blood ccfDNA was successfully used for PCR-based quantification of total amount of cell-free DNA and for methylation analysis as well.

Resistance for Genotoxic Damage in Mesenchymal Stromal Cells Is Increased by Hypoxia but Not Generally Dependent on p53-Regulated Cell Cycle Arrest.

Adult stem cells including multipotent mesenchymal stromal cells (MSC) acquire a high amount of DNA-damage due to their prolonged lifespan. MSC may exert specific mechanisms of resistance to avoid loss of functional activity. We have previously shown that resistance of MSC is associated with an induction of p53 and proliferation arrest upon genotoxic damage. Hypoxia may also contribute to resistance in MSC due to the low oxygen tension in the niche. In this study we characterized the role of p53 and contribution of hypoxia in resistance of MSC to genotoxic damage. MSC exhibited increased resistance to cisplatin induced DNA-damage. This resistance was associated with a temporary G2/M cell cycle arrest, induction of p53- and p21-expression and reduced cyclin B / cdk1-levels upon subapoptotic damage. Resistance of MSC to cisplatin was increased at hypoxic conditions i. e. oxygen <0.5%. However, upon hypoxia the cisplatin-induced cell cycle arrest and expression of p53 and p21 were abrogated. MSC with shRNA-mediated p53 knock-down showed a reduced cell cycle arrest and increased cyclin B / cdk1 expression. However, this functional p53 knock down did not alter the resistance to cisplatin. In contrast to cisplatin, functional p53-knock-down increased the resistance of MSC to etoposide. We conclude that resistance of MSC to genotoxic damage is influenced by oxygen tension but is not generally dependent on p53. Thus, p53-dependent and p53-independent mechanisms of resistance are likely to contribute to the life-long functional activity of MSC in vivo. These findings indicate that hypoxia and different resistance pathways contribute to the phenotype that enables the prolonged lifespan of MSC.