Intra-epithelial neutrophils in paediatric severe asthma are associated with better lung function

BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4.75 (1.6-16) years) underwent clinically indicated fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial brushings and biopsy. Neutrophils, IL-17A and IL-17RA expressing cells and levels of IL-17A and IL-22 were quantified in BAL and biopsies and related to clinical features. Primary bronchial epithelial cells (PBECs) were stimulated with IL-17A and/or IL-22, with and without Budesonide. RESULTS: Children with STRA had increased intra-epithelial neutrophils, which positively correlated with FEV1 %predicted (r=0.43, p=0.008). Neutrophil-high patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in STRA. Submucosal and epithelial IL-17A positive cells and BAL IL-17A and IL-22 levels were similar in STRA and controls. However, there were significantly more IL-17RA positive cells in the submucosa and epithelium in children with STRA compared to controls (p=0.001). Stimulation of PBECs with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of Budesonide. CONCLUSIONS: A proportion of children with STRA exhibit increased intra-epithelial airway neutrophilia that correlated with better lung function. STRA was additionally characterised by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in paediatric severe asthma pathophysiology

BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections.

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias

Radiological outcome of proximal tibia fractures treated with MIPPO – a retrospective study

Background: The concept of minimally invasive Osteosynthesis using percutaneous plate (MIPPO) was established when it is accepted that the length and alignment of proximal tibia can be restored with indirect manipulation aand reduction a technique. Biological fixation with percutaneous plating augments the healing process without additional risk of wound disruption a and infection. Purpose: The aim of the study was to evaluate the radiological outcome of proximal tibial fractures treated with minimal invasive percutaneous plate technique osteosynthesis.Method & Material: The present study is a retrospective cohort study conducted based on the data obtained in the operative registry from the Department of Orthopaedics, during the period of September 2019 to January 2021, at R L Jalappa Hospital, kolar. This study included 32 patients with the fracture proximal tibia treated with MIPPO plating technique and age of patient ranging from 20 to 75 years. All the patients meeting the inclusion and exclusion criteria were included in the study. The radiographic images were taken from the database and classified fractures based on schatzkers classification and were evaluated for the radiological outcome based on union time and Rasmussen’s radiological criteria for the outcome. Result: A total of 32 patients of proximal tibial fractures were treated with minimally invasive percutaneous plate osteosynthesis technique. There were 20(62.5%) were males and 12(37.5%) were females, with patients in the age group of 26-68 years. 17(53.3%) were right sided and 15(46.8%) were left sided. Lateral condyle involved was 17(53%) >bicondylar condyle involved was 8(25%) >medial condyle involved was 7(21%). Road traffic accident evolved as most common (75%) mode of injury. Fractures were classified according to schatzkers classification. Type 1 of fracture seen in 6 (19 %), type 2 in 3 (9%), type 3 in 10 (21.9%) type 4 in 7 (21.9%) type 5 in 5 (15%) patients and type 6 in 2 (6%) patients. Rasmussen’s radiological scoring system was used for final evaluation of the results. According to Rasmussen’s radiological score, in our study we excellent radiological outcome was achieved in 25% (8) of the cases and good outcome was achieved in 40.6% (13) of cases and fair outcome was achieved in 34 % (10) of cases and poor outcome was achieved in 3% (1) of casesConclusion: Minimally invasive percutaneous plate Osteosynthesis is better technique, and should be considered as primary option for the surgical treatment of the proximal tibia fractures. Radiological outcome of MIPPO technique are excellent and good and comparable to world literature in terms of fracture union. MIPPO technique can be successfully used for the simple or compound fracture of proximal tibia