Ferroptosis, a key to unravel the enigma of the FLASH effect?

Ferroptosis is a non-apoptotic form of cell death dependent on iron and lipid peroxides. It has been recently described to have a role on cell death after radiation (RT) through a DNA damage independent mechanism. While the modification of ferroptosis pathways is suggested to enhance radiosensitisation, normal tissue toxicity may limit the combined treatment of RT and ferroptosis inducers. FLASH RT is given at ultra-high dose rates to reduce normal tissue toxicities, which contributes to the RT effect on the tumour. Although several hypotheses including oxygen depletion, reduced ROS, and immune responses are suggested to explain the FLASH effect, the underlying mechanisms of normal tissue sparing effects are still not well understood. Previous studies highlighting the inverse effect of RT dose rates and lipid peroxidation, along with the hypothesis by Spitz et al, suggest that oxygen depletion from the chain reaction of lipid peroxidation and differences in labile pool between normal and tumour tissues may be related to the normal tissue sparing effect of FLASH. Therefore, the role of ferroptosis in ultra-high dose rate FLASH RT needs to be investigated further as it might be the key to increase the therapeutic window of FLASH RT.

Respiratory viral infections among hospitalized adults: experience of a single tertiary healthcare hospital.

BACKGROUND: Following the 2009 H1N1 pandemic, there have been a large number of studies focusing on the epidemiology and outcomes of influenza A infection; however, there have been fewer studies focused on other respiratory viral infections. OBJECTIVES: To define the epidemiology and outcomes of non-influenza respiratory viral infections in hospitalized adults. PATIENTS/METHODS: Data on all patients ≥18 years of age with a positive molecular respiratory viral assay who were hospitalized at a single tertiary healthcare system in Chicago, IL, from retrospectively collected and analyzed. RESULTS: Over the study period, 503 of 46 024 (1·1%) admitted patients had a positive RVP result. Human rhinovirus was the most commonly detected virus followed by influenza A, human metapneumovirus, respiratory syncytial virus, and parainfluenza virus, adenovirus, and influenza B, respectively. Infection in immunocompromised patients was associated with a higher rate of progression to pneumonia and death. CONCLUSIONS: Non-influenza respiratory viral infections are commonly detected among adults admitted to the hospital and can cause serious illness. The data can inform the prioritization of research into novel antiviral therapies for these infections.

An implementation program targeted at non-physician, anaesthesia assistants improves the quality of laryngeal mask anaesthesia.

The laryngeal mask airway (LMA) is used to facilitate adequate ventilation in the majority of procedures requiring general anaesthesia in the UK. Excessive LMA cuff pressure and/or volume, generated by injection of air to form an adequate seal within the upper airway, has been associated with pharyngolaryngeal morbidity, an indicator of quality in anaesthetic practice. However, measurement of LMA cuff pressure to limit excessive cuff pressure is not routine practice, despite trial data showing this reduces adverse outcomes. Our aim was to reduce morbidity from the LMA through the implementation of an educational and interventional program targeted at anaesthetic nurses and operating department assistants (ODA), to alter their physician colleagues' practice. LMA cuff pressure measurements were made, and postoperative outcomes recorded, in an observational cohort of surgical patients over an initial 2-month period. These results, including patient morbidity and the evidence for LMA cuff pressure measurement, were presented to anaesthesia providers and their assistants. An implementation plan to adjust pressures within recommended levels was then undertaken by anaesthesia assistants. In 90 patients, >95% of LMA pressures were beyond the recommended level; higher volumes of injected air correlated with excess pressure (r=0.58; p<0.0001) and were associated with pharyngolaryngeal morbidity in 28% patients (P=0.04). There was no association with difficulty in LMA insertion, duration or type of surgical procedure. In the implementation cohort (102 patients), pharyngolaryngeal morbidity was reduced to 11% (P=0.001) in the 45 patients where LMA cuff pressure was reduced to within normal limits (absolute risk reduction: 38% (95% CI: 22-54%). LMA manometry in three patients (95% CI: 2-5) was required to prevent an episode of postoperative pharyngolaryngeal morbidity. A systematic educational and interventional program targeted at the entire perioperative anaesthesia team, but implemented by anaesthesia assistants, can improve perioperative safety and quality.