BACKGROUNDTracheostomized patients undergoing liberation from mechanical ventilation (MV) are exposed to the ambient environment through humidified air, potentially heightening aerosol particle dispersion. This study was designed to evaluate the patterns of aerosol dispersion during spontaneous breathing trials in such patients weaning from prolonged MV.METHODSParticle Number Concentrations (PNC) at varying distances from tracheostomized patients in a specialized weaning unit were quantified using low-cost particle sensors, calibrated against a Condensation Particle Counter. Different oxygen delivery methods, including T-piece and collar mask both with the humidifier or with a small volume nebulizer (SVN), and simple collar mask, were employed. The PNC at various distances and across different oxygen devices were compared using the Kruskal-Wallis test.RESULTSOf nine patients receiving prolonged MV, five underwent major surgery, and eight were successfully weaned from ventilation. PNCs at distances ranging from 30 cm to 300 cm showed no significant disparity (H(4) = 8.993, p = 0.061). However, significant differences in PNC were noted among oxygen delivery methods, with Bonferroni-adjusted pairwise comparisons highlighting differences between T-piece or collar mask with SVN and other devices.CONCLUSIONAerosol dispersion within 300 cm of the patient was not significantly different, while the nebulization significantly enhances ambient aerosol dispersion in tracheostomized patients on prolonged MV.

01 Sep 2024·Rheumatology

Genetic changes from type I interferons and JAK inhibitors: clues to drivers of juvenile dermatomyositis

Article

Author: Covert, Lauren T ; Truskey, George A ; Prinz, Joseph A ; Swain-Lenz, Devjanee ; Dvergsten, Jeffrey

AbstractObjectiveTo better understand the pathogenesis of juvenile dermatomyositis (JDM), we examined the effect of the cytokines type I interferons (IFN I) and JAK inhibitor drugs (JAKi) on gene expression in bioengineered pediatric skeletal muscle.MethodsMyoblasts from three healthy pediatric donors were used to create three-dimensional skeletal muscle units termed myobundles. Myobundles were treated with IFN I, either IFNα or IFNβ. A subset of IFNβ-exposed myobundles was treated with JAKi tofacitinib or baricitinib. RNA sequencing analysis was performed on all myobundles.ResultsSeventy-six myobundles were analysed. Principal component analysis showed donor-specific clusters of gene expression across IFNα and IFNβ-exposed myobundles in a dose-dependent manner. Both cytokines upregulated interferon response and proinflammatory genes; however, IFNβ led to more significant upregulation. Key downregulated pathways involved oxidative phosphorylation, fatty acid metabolism and myogenesis genes. Addition of tofacitinib or baricitinib moderated the gene expression induced by IFNβ, with partial reversal of upregulated inflammatory and downregulated myogenesis pathways. Baricitinib altered genetic profiles more than tofacitinib.ConclusionIFNβ leads to more pro-inflammatory gene upregulation than IFNα, correlating to greater decrease in contractile protein gene expression and reduced contractile force. JAK inhibitors, baricitinib more so than tofacitinib, partially reverse IFN I-induced genetic changes. Increased IFN I exposure in healthy bioengineered skeletal muscle leads to IFN-inducible gene expression, inflammatory pathway enrichment, and myogenesis gene downregulation, consistent with what is observed in JDM.

01 May 2024·Lung India

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study

Article

Author: Sundaram, Dhivya ; Sahoo, Alok Kumar ; Sharma, Arun ; Rao, Parnandi Bhaskar ; Joshi, Krupal ; Sreedevi, Billa PS ; Agarwal, Sonika ; Kothari, Nikhil ; Singhal, Sanjay ; Sivaramakrishnan, Prakash ; Mukherjee, Sudipta ; Katoch, Chandan Dev Singh ; Saran, Sai ; Deokar, Kunal ; Gurjar, Mohan ; Sahoo, Jyoti Narayan ; Dua, Ruchi ; Ghosh, Pralay Shankar ; Singh, Umadri ; Agrawal, Avinash ; Sharma, Ankur ; Sharma, Prakhar

Background:In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs).Methods:After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device.Results:From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV.Conclusion:Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

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Indication	Highest Phase	Country/Location	Organization	Date
Herpes Simplex	Phase 2	CN	Beijing Kawin Technology Share-Holding Co., Ltd.	27 Apr 2023
Herpangina	Phase 2	-	Beijing Kawin Technology Share-Holding Co., Ltd.	-

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