Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Contribution of Multisensory Stimuli to the Representation of Space in the Hippocampus and Medial Entorhinal Cortex

How the brain integrates information over multiple sensory modalities to encode highly complex stimuli is a central question of neuroscience. The mammalian brain structures that encode space provide a tractable system in which to explore this question, as there are several well-defined cell types that have spatially selective firing. Place cells in the hippocampus fire when an animal is in a particular location in the environment. Grid cells, found in the upstream medial entorhinal cortex (MEC), have multiple firing fields located on the vertices of a triangular grid. Also found in the MEC are border cells that fire along the boundaries of an environment, and head direction (HD) cells that fire when the animal’s head is facing a particular direction. Using virtual reailty for rats, we explored the contribtion of multiple sensory modalities to the spatial selectivity of these cell types.The hippocampal cognitive map is thought to be driven by distal visual cues and self-motion cues. In VR place cells showed robust spatial selectivity, however a much smaller proportion were track active, compared to the RW. This indicates that distal visual and non-vestibular self-motion cues are indeed sufficient to provide selectivity, but vestibular and other sensory cues present in RW are necessary to fully activate the place cell population. Additionally, bidirectional cells preferentially encoded distance along the track in VR, but encoded absolute position in RW. Taken together these results suggest the differential contributions of sensory cues in shaping the hippocampal population code.Similarly, we also measured the activity of grid cells and head direction cells in open field environments in VR and RW. Here, we found that grid cells lost their spatial selectivity and periodicity, demonstrating that the cues available in the VR were insufficient. Most HD cells, likewise, did not retain their directional tuning in a body-fixed VR, suggesting that visual cues might maintain only a partial ability to update the firing directions of HD cells in the absence of reliable angular vestibular cues. However, a small portion of HD cells found to maintain their selectivity in the VR warrant further investigation.These results provide insight to the contributions of individual sensory modalities to the firing of spatially selective cell types, as well as the mental representation of space

Multisensory control of multimodal behavior: do the legs know what the tongue is doing?

Understanding of adaptive behavior requires the precisely controlled presentation of multisensory stimuli combined with simultaneous measurement of multiple behavioral modalities. Hence, we developed a virtual reality apparatus that allows for simultaneous measurement of reward checking, a commonly used measure in associative learning paradigms, and navigational behavior, along with precisely controlled presentation of visual, auditory and reward stimuli. Rats performed a virtual spatial navigation task analogous to the Morris maze where only distal visual or auditory cues provided spatial information. Spatial navigation and reward checking maps showed experience-dependent learning and were in register for distal visual cues. However, they showed a dissociation, whereby distal auditory cues failed to support spatial navigation but did support spatially localized reward checking. These findings indicate that rats can navigate in virtual space with only distal visual cues, without significant vestibular or other sensory inputs. Furthermore, they reveal the simultaneous dissociation between two reward-driven behaviors

Environmental Samples Test Negative for Avian Influenza Virus H5N1 Four Months after Mass Mortality at A Seabird Colony

High pathogenicity avian influenza (HPAI) profoundly impacted several seabird populations during the summers of 2021 and 2022. Infection spread rapidly across colonies, causing unprecedented mortality. At Foula, Shetland, 1500 breeding adult great skuas Stercorarius skua, totalling about two tonnes of decomposing virus-laden material, died at the colony in May−July 2022. Carcasses were left where they died as Government policy was not to remove dead birds. The factors influencing risk of further spread of infection are uncertain, but evidence suggests that HPAI can persist in water for many months in cool conditions and may be a major transmission factor for birds living in wetlands. We investigated risk of further spread of infection from water samples collected from under 45 decomposing carcasses and in three freshwater lochs/streams by sampling water in October 2022, by which time the great skua carcasses had rotted to bones, skin, and feathers. No viral genetic material was detected four months after the mortality, suggesting a low risk of seabird infection from the local environment when the seabirds would return the next breeding season. These findings, although based on a relatively small number of water samples, suggest that the high rainfall typical at Shetland probably washed away the virus from the decomposing carcasses. However, limitations to our study need to be taken on board in the design of environmental monitoring at seabird colonies during and immediately after future outbreaks of HPAI

Multisensory Control of Multimodal Behavior: Do the Legs Know What the Tongue Is Doing?

<div><p>Understanding of adaptive behavior requires the precisely controlled presentation of multisensory stimuli combined with simultaneous measurement of multiple behavioral modalities. Hence, we developed a virtual reality apparatus that allows for simultaneous measurement of reward checking, a commonly used measure in associative learning paradigms, and navigational behavior, along with precisely controlled presentation of visual, auditory and reward stimuli. Rats performed a virtual spatial navigation task analogous to the Morris maze where only distal visual or auditory cues provided spatial information. Spatial navigation and reward checking maps showed experience-dependent learning and were in register for distal visual cues. However, they showed a dissociation, whereby distal auditory cues failed to support spatial navigation but did support spatially localized reward checking. These findings indicate that rats can navigate in virtual space with only distal visual cues, without significant vestibular or other sensory inputs. Furthermore, they reveal the simultaneous dissociation between two reward-driven behaviors.</p></div

Navigational performance and reward checking during the auditory and visual virtual spatial navigation tasks.

<p>(A) Schematic of the auditory task and the visual task. Symbols as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080465#pone-0080465-g003" target="_blank">Figure 3</a>. (B) Example paths from each task. (C) 2-D histogram of occupancy averaged across rats over 4 sessions for each trial type. (D) 2-D histogram of the normalized check rate averaged across rats over these sessions. White areas indicate insufficient coverage. (E) Percentage of occupancy and check rate in the target quadrant for the two tasks. Two way ANOVA for effect target vs. other quadrants and auditory vs. visual trial types: Effect of quadrant F(1,8)  = 95.16, p< 0.001, Effect of task type: F(1,8)  = 2.08, p<0.001, Interaction of quadrant and task type: F(1,8)  = 2.08, p = 0.002; Effect of quadrant for auditory task: p = 0.097, target quadrant percentage occupancy: 23.9±0.5% vs. mean non-target occupancy: 25.36±0.17%, note that occupancy is slightly decreased in the target quadrant as animals entering the reward zone are teleported out; for visual task: p<0.001, target quadrant percentage occupancy: 59.6±1.15% vs. mean non-target occupancy: 13.5±0.38%, N = 5. (F) Normalized check rate as a function of distance away from the reward zone in radial bins for both trial types. Effect of distance from reward: F(14,112)  = 67.11, p<0.0001, p> 0.05 for effects of task type and interaction.</p

Multisensory contribution to virtual spatial navigation and reward checking.

<p>(A) Schematic of the Audiovisual (AV), Visual (V) only and Auditory (A) virtual spatial mazes. Symbols as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080465#pone-0080465-g001" target="_blank">Figure 1</a>. (B) Example paths for the three trial types from a single rat. The color of each path indicates start location, color coded from the arrows in A. (C) Median latency and distance to reward for each trial type. Effect of trial type, F(2,17)  = 7.555, p = 0.01, F(2,17)  = 8.911, p = 0.006, respectively. A vs. AV and V: p<0.05 for both measures, N = 6. (D) Percentage occupancy in the target quadrant for the three trial types. Effect of trial type: F(2,17)  = 13.19, p = 0.0064. A vs. AV: p = 0.013, A and V: p = 0.018.</p