Health-related quality of life after 12 months post discharge in patients hospitalised with COVID-19-related severe acute respiratory infection (SARI): a prospective analysis of SF-36 data and correlation with retrospective admission data on age, disease severity, and frailty.

Long-term outcome and 'health-related quality of life' (HRQoL) following hospitalisation for COVID-19-related severe acute respiratory infection (SARI) is limited. OBJECTIVE: To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity. METHOD: Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (<49, 49-69, and the over 69-year-olds), the relative impact of frailty (using the Clinical Frailty Score; CFS), and disease severity (using National Early Warning Score; NEWS) on HRQoL domains. RESULTS: Overall mortality was 46.5% in admitted patients. In our SF-36 cohort (n=169), there was a significant reduction in all HRQoL domains versus normative data; the most significant reductions were in the physical component (p<0.001) across all ages and the emotional component (p<0.01) in the 49-69 year age group, with age having no additional impact on HRQoL. However, there was a significant correlation between physical well-being versus CFS (the correlation coefficient=-0.37, p<0.05), though not NEWS, with no gender difference observed. CONCLUSION: There was a significant reduction in all SF-36 domains at 1 year. Poor CFS at admission was associated with a significant and prolonged impact on physical parameters at 1 year. Age had little impact on the severity of HRQoL, except in the domains of physical functioning and the overall physical component.

Transtracheal jet ventilation in a general tertiary hospital: A 7-year audit.

Airway management in patients presenting with severe airway obstruction can present a challenge to the anaesthetist, as conventional difficult airway pathways are often inappropriate. The use of a transtracheal jet cannula is an alternative means of airway securement, but lack of familiarity has limited its use in general tertiary hospitals. We report a retrospective audit of the use of transtracheal jet ventilation in a general tertiary healthcare centre over the past seven years, with a total of 50 patients with severe airway compromise undergoing pharyngolaryngeal surgery. Transtracheal jet ventilation was successful in 98% of patients, and was the definitive means of airway management in 43 cases. In six cases, the technique was a useful temporising measure while the airway was secured by other means. Minor complications occurred in 12% of patients. No major morbidities or mortalities were recorded. We conclude that transtracheal jet ventilation for high-risk pharyngolaryngeal surgery can be performed using a high frequency jet ventilator, with a high rate of success and only minor complications. Cannulation of the trachea below the cricothyroid membrane is feasible but more challenging. Low-flow apnoeic oxygenation through the transtracheal jet ventilation cannula maintains oxygenation during initial surgical airway manipulation.

Corynebacterium kroppenstedtii Is an Emerging Cause of Mastitis Especially in Patients With Psychiatric Illness on Antipsychotic Medication.

This retrospective study of patients with Corynebacterium kroppenstedtii infections revealed a predominance of mastitis and a potential association with psychiatric illnesses. At least one third of our patients with C kroppenstedtii mastitis had psychiatric illness, and >92% received antipsychotic medications. Drug-induced hyperprolactinemia may be an important modifiable risk factor in these patients.

PGC-1α rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function.

Huntington's disease (HD) is caused by CAG repeat expansions in the huntingtin (htt) gene, yielding proteins containing polyglutamine repeats that become misfolded and resist degradation. Previous studies demonstrated that mutant htt interferes with transcriptional programs coordinated by the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α), a regulator of mitochondrial biogenesis and oxidative stress. We tested whether restoration of PGC-1α could ameliorate the symptoms of HD in a mouse model. We found that PGC-1α induction virtually eliminated htt protein aggregation and ameliorated HD neurodegeneration in part by attenuating oxidative stress. PGC-1α promoted htt turnover and the elimination of protein aggregates by activating transcription factor EB (TFEB), a master regulator of the autophagy-lysosome pathway. TFEB alone was capable of reducing htt aggregation and neurotoxicity, placing PGC-1α upstream of TFEB and identifying these two molecules as important therapeutic targets in HD and potentially other neurodegenerative disorders caused by protein misfolding.