A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

Blue delayed luminescence emission in neutral nitrogen vacancy containing chemical vapor deposition synthetic diamond

Herein, the authors investigate the temperature‐dependent properties of delayed luminescence in an as‐grown nitrogen‐containing chemical vapor deposition synthetic diamond gemstone when excited above its bandgap. At room temperature, this gemstone exhibits delayed luminescence from nitrogen‐vacancy centers at 575 nm. However, at 77 K, the first recorded instance of a long‐lived delayed blue luminescence centered at ≈465 nm, accompanied by spectral peaks at 419, 455, and 499 nm is reported. By analyzing spectral and temporal data at different temperatures, it can be speculated on potential photophysical transitions. This discovery documents the initial observation of this delayed luminescence emission, contributing to the collective understanding of synthetic diamonds

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

A retrospective analysis of the prevalence and clinical outcomes of vitamin D deficiency in myeloma patients in tropical Australia

Purpose The aim of this descriptive study was to assess the prevalence of vitamin D deficiency in patients on active therapy for multiple myeloma in a tropical climate. We also tested for the association of vitamin D status on clinical outcomes. Methods This was a single centre, observational study performed in Townsville, Australia, which has a sunlight heavy, tropical climate. Patients on active therapy for multiple myeloma underwent testing of serum 25-hydroxyvitamin D (25(OH)D). Information on disease stage, skeletal morbidity and symptoms of peripheral neuropathy were collected from medical records and self-reported patient questionnaires. Results A total of 41 patients were included. With a median disease duration of 38 months, 27% were found to be vitamin D deficient. Patients with vitamin D deficiency had a higher likelihood of peripheral neuropathy compared with their non-vitamin D counterparts (73% vs. 33%, P = 0.03). Although those with vitamin D deficiency had more skeletal morbidity, this was not statistically significant (73% vs 50%, P = 0.19). Reduced 25(OH) D was associated with a poor performance status (P = 0.003). There was no association between vitamin D status and stage of myeloma. Conclusion There is a relatively high prevalence of vitamin D deficiency in patients with myeloma in our study. This is despite a sunlight heavy, tropical climate. We report an association between vitamin D deficiency and peripheral neuropathy. Prospective interventional trials are required to further assess this

A comprehensive study of the epidemiology of haematological malignancies in North Queensland

Background: There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. Aim: To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. Methods: Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005-2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematologic malignancies by geographic regions. Results: 1581 haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data is presented for 58 major subtypes as per the WHO diagnostic classification of tumours of haematopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematologic malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100,000 ranging from 0.5 to 233.5. Our data suggests an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared to other regions. Conclusion: This study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive, and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications toward developing appropriate data-driven management strategies and public health responses for haematological malignancies