Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections.

Tigecycline (TIG) is a broad-spectrum antibiotic that has been approved for the treatment of a number of complicated infections, including community-acquired bacterial pneumonia. Currently it is available only as an intravenous injection that undergoes rapid chemical degradation and limits the use to in-patient scenarios. The use of TIG as an inhaled dry powder inhaler may offer a promising treatment option for patients with multidrug-resistant respiratory tract infections, such as Stenotrophomonas maltophilia (S. maltophilia). This study explores the feasibility of engineering an inhaled powder formulation of TIG that could administer relevant doses at a wide range of inhalation flow rates while maintaining stability of this labile drug. Using air-jet milling, micronized TIG had excellent aerosolization efficiency, with over 80% of the device emitted dose being within the respirable range. TIG was also readily dispersed using different inhaler devices even when tested at different pressure drops and flow rates. Additionally, micronized TIG was stable for 6 months at 25 °C/60% RH and 40 °C/75% RH. Micronized TIG maintained a low minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of 0.8 µM and >0.5 µM, respectively in S. maltophilia cultures in vitro. These results strongly suggest that the micronization of TIG results in a stable and respirable formulation that can be delivered via the pulmonary route for the treatment of lung infections.

Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage. Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking. METHODS: Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years. We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits. RESULTS: Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates. Virus infection was strongly associated with exacerbation events (P < 5E-20). Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation. Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event. Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung. CONCLUSIONS: This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations. It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications.

Buccal delivery of small molecules and biologics: Of mucoadhesive polymers, films, and nanoparticles - An update.

Buccal delivery of small and large molecules is an attractive route of administration that has been studied extensively over the past few decades. This route bypasses first-pass metabolism and can be used to deliver therapeutics directly to systemic circulation. Moreover, buccal films are efficient dosage forms for drug delivery due to their simplicity, portability, and patient comfort. Films have traditionally been formulated using conventional techniques, including hot-melt extrusion and solvent casting. However, newer methods are now being exploited to improve the delivery of small molecules and biologics. This review discusses recent advances in buccal film manufacturing, using the latest technologies, such as 2D and 3D printing, electrospraying, and electrospinning. This review also focuses on the excipients used in the preparation of these films, with emphasis on mucoadhesive polymers and plasticizers. Along with advances in manufacturing technology, newer analytical tools have also been used for the assessment of permeation of the active agents across the buccal mucosa, the most critical biological barrier and limiting factor of this route. Additionally, preclinical and clinical trial challenges are discussed, and some small molecule products already on the market are explored.

Unilocular thymic cyst with features of intra-thymic bronchogenic cyst: A clinicopathological correlation of 4 cases.

Four cases of primary unilocular thymic with features of bronchogenic cyst are presented. The patients are three men and a woman between the ages of 43 and 57 years. All the patients presented with symptoms of cough, chest pain, and dyspnea. Diagnostic imaging revealed the presence of an anterior mediastinal cystic lesion. Initial mediastinoscopic biopsies were non-diagnostic. Surgical resection of the anterior mediastinal cystic lesion was performed in all patients. Macroscopically, all the lesions were described as large cystic lesions measuring from 2 to 4 cm in largest diameter and containing yellowish fluid. The surface of the cysts was described as corrugated and of brownish color. The walls of the cysts were not thickened and no other elements were described. Histologically, the cystic lesions were characterized by single cystic structures lined by ciliated epithelium. No atypia or mitotic activity was present in any of the cases. Immunohistochemical stains show positive staining of the respiratory epithelium with keratin and negative staining for GATA3, PAX-8, TTF-1, and Napsin. All the patients have recovered well after surgical resection.

Strengthening tobacco control policies during the COVID-19 pandemic in India.

Problem considered: The aim of this paper was to support policy makers to make informed decisions regarding public health response in general, and tobacco control interventions particularly, in the context of COVID-19. Methods: An online cross-sectional survey using a semi-structured questionnaire was conducted in the year 2020 with stakeholders in tobacco control and public health experts from private and government organizations. Information pertaining to background characteristics of study participants and impact of pandemic on tobacco use and means to leverage tobacco control policy was collected. Data was analysed using Microsoft excel 2010 and results are presented as frequencies and percentages along with key responses from open ended questions. Results: A total of 72 stakeholders were approached out of which, 46 (56.1%) responded and were included. About 32 (74.4%) of the participants thought that public health authorities had given advice on stopping tobacco use during COVID-19 pandemic. About 19 (43.2%) participants did not notice any change in level of interest in tobacco cessation during the pandemic while a majority 34(73.8%) agreed that COVID-19 pandemic had an impact on health seeking behaviour of patients with non-communicable diseases. Nearly half of participants, 21(48.8%) opined that tobacco industry was engaged in corporate social responsibilities during COVID-19. Conclusion: The stakeholders expressed that there is a good opportunity to further strengthen tobacco control activities during COVID-19 pandemic and also emphasized need to closely monitor tobacco industry interference during this time.

Building a smart FNA cart: When Google meets cytology.

BACKGROUND: The appropriate management of a fine needle aspiration (FNA) supply cart and equipment set up is essential to ensure the smooth and optimal operation of a busy FNA clinic. We applied Lean strategies such as value stream mapping (VSM), the 5S method (Sort, Set in order, Shine, Standardize, Sustain), and Kanban to remove waste and improve patient flow in an FNA clinic. METHODS: The workflow analysis suggested that existent problems such as suboptimal inventory management and unavailability of standard operating procedures (SOPs) caused a 10% to 85% increase in total procedure time. To improve inventory management, we created a 2-bin Kanban system. We used the "Scan to Web" app and a Google Drive form to create a cost-effective electronic inventory management system. We distributed the essential SOPs in the format of video clips using our YouTube channel and leveraged barcode technology to access the links. RESULTS: Upon completion of our process improvement project, we succeeded to eliminate the stock-out events and maintain a process cycle efficiency of 87%. The 5S audit checklist result increased from 6% to 100% implementation, which is consistent with focused improvement. The developed inventory system enabled us to track the supply usage, forecast demands, and improve the accuracy of orders. CONCLUSIONS: Lean methods such as VSM, 5S, and Kanban combined with open source technologies can be implemented to ensure material availability, track inventory, and provide immediate access to SOPs on demand. The developed system also led to increased efficiency and improved flow, as well as responsiveness to changes in demand.