Epidemiological trends of respiratory tract pathogens detected via mPCR in Australian adult patients before COVID-19.

BACKGROUND: Respiratory tract infections (RTIs) are a major global health burden due to their high morbidity and mortality. This retrospective study described the epidemiology of respiratory pathogens in adults over a 5-year period at an Australian tertiary healthcare network. METHODS: All multiplex reverse transcription polymerase chain reaction respiratory samples taken between the 1st of November 2014 and the 31st of October 2019 were included in this study. Overall prevalence and variations according to seasons, age groups and sex were analysed, as well as factors associated with prolonged hospital and intensive care length of stay. RESULTS: There were 12,453 pathogens detected amongst the 12,185 positive samples, with coinfection rates of 3.7%. Picornavirus (Rhinovirus), Influenza A and respiratory syncytial virus were the most commonly detected pathogens. Mycoplasma pneumoniae was the most commonly detected atypical bacteria. Significant differences in the prevalence of Chlamydia pneumoniae and Human metapneumovirus infections were found between sexes. Longest median length of intensive care and hospital stay was for Legionella species. Seasonal variations were evident for certain pathogens. CONCLUSIONS: The high rates of pathogen detection and hospitalisation in this real-world study highlights the significant burden of RTIs, and the urgent need for an improved understanding of the pathogenicity as well as preventative and treatment options of RTIs.

Respiratory Infection and Inflammation in Cystic Fibrosis: A Dynamic Interplay among the Host, Microbes, and Environment for the Ages.

The interplay between airway inflammation and infection is now recognized as a major factor in the pathobiology in cystic fibrosis (CF). A proinflammatory environment is seen throughout the CF airway resulting in classic marked and enduring neutrophilic infiltrations, irreversibly damaging the lung. Although this is seen to occur early, independent of infection, respiratory microbes arising at different timepoints in life and the world environment perpetuate this hyperinflammatory state. Several selective pressures have allowed for the CF gene to persist until today despite an early mortality. Comprehensive care systems, which have been a cornerstone of therapy for the past few decades, are now revolutionized by CF transmembrane conductance regulator (CTFR) modulators. The effects of these small-molecule agents cannot be overstated and can be seen as early as in utero. For an understanding of the future, this review looks into CF studies spanning the historical and present period.

Reduced dendritic arborization and hyperexcitability of pyramidal neurons in a Scn1b-based model of Dravet syndrome.

Epileptic encephalopathies, including Dravet syndrome, are severe treatment-resistant epilepsies with developmental regression. We examined a mouse model based on a human ß1 sodium channel subunit (Scn1b) mutation. Homozygous mutant mice shared phenotypic features and pharmaco-sensitivity with Dravet syndrome. Patch-clamp analysis showed that mutant subicular and layer 2/3 pyramidal neurons had increased action potential firing rates, presumably as a consequence of their increased input resistance. These changes were not seen in L5 or CA1 pyramidal neurons. This raised the concept of a regional seizure mechanism that was supported by data showing increased spontaneous synaptic activity in the subiculum but not CA1. Importantly, no changes in firing or synaptic properties of gamma-aminobutyric acidergic interneurons from mutant mice were observed, which is in contrast with Scn1a-based models of Dravet syndrome. Morphological analysis of subicular pyramidal neurons revealed reduced dendritic arborization. The antiepileptic drug retigabine, a K+ channel opener that reduces input resistance, dampened action potential firing and protected mutant mice from thermal seizures. These results suggest a novel mechanism of disease genesis in genetic epilepsy and demonstrate an effective mechanism-based treatment of the disease.

Lane-Hamilton syndrome.

The co-existence of idiopathic hemosiderosis and celiac disease is Lane-Hamilton Syndrome. This is a rare condition with only a few dozen cases reported to date. Its clinical presentation typically involves hemoptysis that can be life-threatening in the acute phase. We report the uncommon case of the development of idiopathic pulmonary hemosiderosis almost a decade after the diagnosis of celiac disease. Delayed diagnosis led to recurrent episodes of large volume hemoptysis despite immunosuppressive therapy due to ongoing ingestion of gluten. High doses of glucocorticoids accompanied by a cell cycle inhibitor mycophenolate mofetil were required for treatment. A strict gluten free diet is vital to control the disease. We highlight the importance of identifying this syndrome and definitive treatment, including avoidance of dietary triggers in addition to conventional immunosuppressive therapy.

Lessons from the contrast dye shortage during COVID-19: A narrative review.

The sudden contrast dye shortage, precipitated by a temporary forced closure of healthcare plant, has limited the supply of iodinated contrast media to Australia. Furthering the impact of the coronavirus disease 2019 pandemic, this new crisis has increased burden on the radiology system. Lessons from the strategies applied during the shortage should be used as building blocks as safeguards for the future. A pragmatic approach to education and training is required in an ever-changing environment. Our relationships between medical specialties and manufacturers are paramount to maintaining an effective workflow. An ongoing commitment to a strong workforce will be the backbone to overcome another challenge in these uncertain times.

Relapsing polychondritis with large airway involvement.

Relapsing polychondritis is a rare autoimmune condition characterized by episodic and progressive cartilaginous inflammation. Its clinical presentation is vastly divergent and can affect various organs. We report the uncommon case of large airway involvement in a patient presenting with shortness of breath on the background of diagnosed relapsing polychondritis. Computed tomography (CT) chest demonstrated thickening of the cartilaginous portions of the trachea and bronchi with sparing of the posterior membranes, consistent with tracheobronchomalacia and repeated cartilaginous destruction. High doses of systemic glucocorticoids, accompanied by continuous positive airway pressure, were required for treatment. We highlight the importance of identifying the extent of airways affected and definitive positive airway pressure support for relapsing polychondritis affecting major airways in addition to conventional therapy of immunosuppression.

Endobronchial tuberculosis polyps.

Endobronchial tuberculosis (TB) is an uncommon manifestation of Mycobacterium tuberculosis. We report a case of endobronchial TB polyps in a patient from India presenting with cough, loss of weight and night sweats. Computed tomography chest revealed enlarged mediastinal lymph nodes, endobronchial invasion, and nodular infiltrates in the right lower lobe. Flexible bronchoscopy revealed two endobronchial polyps at the carina and left main bronchus which were biopsied. Histopathology showed non-caseating granulomas. Both the biopsy and bronchial washings did not identify acid-fast bacilli on Ziehl-Neelsen stain and had negative TB complex DNA polymerase chain reaction. One month after bronchoscopy, M. tuberculosis was cultured from the bronchial washings. Following six months of TB treatment, there was full resolution of symptoms and significant radiological improvement. We highlight the diagnostic challenges in endobronchial TB which may impact on the timely institution of treatment.

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

BACKGROUND: Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality. METHODS: We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated. RESULTS: The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p = 0.2). CONCLUSIONS: Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.

A complicated cockroach-ectomy.

The exact incidence of foreign body aspiration among adults is unknown, and its clinical presentation is vastly divergent. We report the previously undescribed occurrence of cockroach aspiration in an adult, presenting with a "crawling sensation" in his chest. Flexible endobronchial examination revealed a foreign body impacted in the lingula, resembling the Australian cockroach Periplaneta australasiae. Partial extraction via biopsy forceps was performed and complicated by acute hypoxia on disimpaction, requiring a brief period of bag/mask ventilation. Following the offset of procedural sedation, the remaining foreign body was manually expectorated. A total of 24 h post-procedure, the patient was febrile with positive blood cultures (Micrococcus luteus). We highlight the importance of definitive airway support during endobronchial interventions and raise the question regarding the significance of transient bacteraemia following bronchoscopic manipulation.