Peripheral Nerve Blocks and Potentially Attributable Adverse Events in Older People with Hip Fracture: A Retrospective Population-based Cohort Study.

BACKGROUND: Peripheral nerve blocks are being used with increasing frequency for management of hip fracture-related pain. Despite converging evidence that nerve blocks may be beneficial, safety data are lacking. This study hypothesized that peripheral nerve block receipt would not be associated with adverse events potentially attributable to nerve blocks, as well as overall patient safety incidents while in hospital. METHODS: This was a preregistered, retrospective population-based cohort study using linked administrative data. This study identified all hip fracture admissions in people 50 yr of age or older and identified all nerve blocks (although we were unable to ascertain the specific anatomic location or type of block), potentially attributable adverse events (composite of seizures, fall-related injuries, cardiac arrest, nerve injury), and any patient safety events using validated codes. The study also estimated the unadjusted and adjusted association of nerve blocks with adverse events; adjusted absolute risk differences were also calculated. RESULTS: In total, 91,563 hip fracture patients from 2009 to 2017 were identified; 15,631 (17.1%) received a nerve block, and 5,321 (5.8%; 95% CI, 5.7 to 6.0%) patients experienced a potentially nerve block-attributable adverse event: 866 (5.5%) in patients with a block and 4,455 (5.9%) without a block. Before and after adjustment, nerve blocks were not associated with potentially attributable adverse events (adjusted odds ratio, 1.05; 95% CI, 0.97 to 1.15; and adjusted risk difference, 0.3%, 95% CI, -0.1 to 0.8). CONCLUSIONS: The data suggest that nerve blocks in hip fracture patients are not associated with higher rates of potentially nerve block-attributable adverse events, although these findings may be influenced by limitations in routinely collected administrative data.

Insights Into Type I and III Interferons in Asthma and Exacerbations.

Asthma is a highly prevalent, chronic respiratory disease that impacts millions of people worldwide and causes thousands of deaths every year. Asthmatics display different phenotypes with distinct genetic components, environmental causes, and immunopathologic signatures, and are broadly characterized into type 2-high or type 2-low (non-type 2) endotypes by linking clinical characteristics, steroid responsiveness, and molecular pathways. Regardless of asthma severity and adequate disease management, patients may experience acute exacerbations of symptoms and a loss of disease control, often triggered by respiratory infections. The interferon (IFN) family represents a group of cytokines that play a central role in the protection against and exacerbation of various infections and pathologies, including asthma. Type I and III IFNs in particular play an indispensable role in the host immune system to fight off pathogens, which seems to be altered in both pediatric and adult asthmatics. Impaired IFN production leaves asthmatics susceptible to infection and with uncontrolled type 2 immunity, promotes airway hyperresponsiveness (AHR), and inflammation which can lead to asthma exacerbations. However, IFN deficiency is not observed in all asthmatics, and alterations in IFN expression may be independent of type 2 immunity. In this review, we discuss the link between type I and III IFNs and asthma both in general and in specific contexts, including during viral infection, co-infection, and bacterial/fungal infection. We also highlight several studies which examine the potential role for type I and III IFNs as asthma-related therapies.

The MyMOMA domain of MYO19 encodes for distinct Miro-dependent and Miro-independent mechanisms of interaction with mitochondrial membranes.

MYO19 interacts with mitochondria through a C-terminal membrane association domain (MyMOMA). Specific mechanisms for localization of MYO19 to mitochondria are poorly understood. Using promiscuous biotinylation data in combination with existing affinity-capture databases, we have identified a number of putative MYO19-interacting proteins. We chose to explore the interaction between MYO19 and the mitochondrial GTPase Miro2 by expressing mchr-Miro2 in combination with GFP-tagged fragments of the MyMOMA domain and assaying for recruitment of MYO19-GFP to mitochondria. Coexpression of MYO19898-970 -GFP with mchr-Miro2 enhanced MYO19898-970 -GFP localization to mitochondria. Mislocalizing Miro2 to filopodial tips or the cytosolic face of the nuclear envelope did not recruit MYO19898-970 -GFP to either location. To address the kinetics of the Miro2/MYO19 interaction, we used FRAP analysis and permeabilization-activated reduction in fluorescence analysis. MyMOMA constructs containing a putative membrane-insertion motif but lacking the Miro2-interacting region displayed slow exchange kinetics. MYO19898-970 -GFP, which does not include the membrane-insertion motif, displayed rapid exchange kinetics, suggesting that MYO19 interacting with Miro2 has higher mobility than MYO19 inserted into the mitochondrial outer membrane. Mutation of well-conserved, charged residues within MYO19 or within the switch I and II regions of Miro2 abolished the enhancement of MYO19898-970 -GFP localization in cells ectopically expressing mchr-Miro2. Additionally, expressing mutant versions of Miro2 thought to represent particular nucleotide states indicated that the enhancement of MYO19898-970 -GFP localization is dependent on Miro2 nucleotide state. Taken together, these data suggest that membrane-inserted MYO19 is part of a larger complex, and that Miro2 plays a role in integration of actin- and microtubule-based mitochondrial activities.