Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs flexible spatial memory in the rat.

In a changing environment, animals must process spatial signals in a flexible manner. The rat hippocampal formation projects directly upon the retrosplenial cortex, with most inputs arising from the dorsal subiculum and terminating in the granular retrosplenial cortex (area 29). The present study examined whether these same projections are required for spatial working memory and what happens when available spatial cues are altered. Consequently, injections of iDREADDs were made into the dorsal subiculum of rats. In a separate control group, GFP-expressing adeno-associated virus was injected into the dorsal subiculum. Both groups received intracerebral infusions within the retrosplenial cortex of clozapine, which in the iDREADDs rats should selectively disrupt the subiculum to retrosplenial projections. When tested on reinforced T-maze alternation, disruption of the subiculum to retrosplenial projections had no evident effect on the performance of those alternation trials when all spatial-cue types remained present and unchanged. However, the same iDREADDs manipulation impaired performance on all three alternation conditions when there was a conflict or selective removal of spatial cues. These findings reveal how the direct projections from the dorsal subiculum to the retrosplenial cortex support the flexible integration of different spatial cue types, helping the animal to adopt the spatial strategy that best meets current environmental demands.

Collateral rostral thalamic projections to prelimbic, infralimbic, anterior cingulate and retrosplenial cortices in the rat brain.

As the functional properties of a cortical area partly reflect its thalamic inputs, the present study compared collateral projections arising from various rostral thalamic nuclei that terminate across prefrontal (including anterior cingulate) and retrosplenial areas in the rat brain. Two retrograde tracers, fast blue and cholera toxin B, were injected in pairs to different combinations of cortical areas. The research focused on the individual anterior thalamic nuclei, including the interanteromedial nucleus, nucleus reuniens and the laterodorsal nucleus. Of the principal anterior thalamic nuclei, only the anteromedial nucleus contained neurons reaching both the anterior cingulate cortex and adjacent cortical areas (prefrontal or retrosplenial), though the numbers were modest. For these same cortical pairings (medial prefrontal/anterior cingulate and anterior cingulate/retrosplenial), the interanteromedial nucleus and nucleus reuniens contained slightly higher proportions of bifurcating neurons (up to 11% of labelled cells). A contrasting picture was seen for collaterals reaching different areas within retrosplenial cortex. Here, the anterodorsal nucleus, typically provided the greatest proportion of bifurcating neurons (up to 15% of labelled cells). While individual neurons that terminate in different retrosplenial areas were also found in the other thalamic nuclei, they were infrequent. Consequently, these thalamo-cortical projections predominantly arise from separate populations of neurons with discrete cortical termination zones, consistent with the transmission of segregated information and influence. Overall, two contrasting medial-lateral patterns of collateral projections emerged, with more midline nuclei, for example, nucleus reuniens and the interoanteromedial nucleus innervating prefrontal areas, while more dorsal and lateral anterior thalamic collaterals innervated retrosplenial cortex.

Virtual reality intervention effects on future self-continuity and delayed reward preference in substance use disorder recovery: pilot study results.

Sustained remission from substance use disorder (SUD) is challenged by high relapse rates, which provides opportunities for novel clinical interventions. Immersive virtual reality (VR) permits delivering synthetic experiences that feel real and actualizes otherwise impossible scenarios for therapeutic benefit. We report on the feasibility of an immersive VR intervention designed to increase valuation of the future by enhancing future self-continuity and leveraging future self-discrepancy with personalized future selves as SUD recovery support. Twenty-one adults in early SUD recovery (< 1 year) interacted with versions of themselves age-progressed fifteen years from two different behavioral trajectories: an SUD Future Self and a Recovery Future Self. The future selves' interactive monologs include personalized details and voice for a lifelike interaction within a time travel vignette. Before and following the intervention, participants rated future self-continuity and performed delay discounting. Following the intervention, daily images of the Recovery Future Self were sent to participants' smartphones for thirty days. The VR intervention generated no adverse events, was well tolerated (presence, liking, and comfort), and significantly increased future self-continuity and delayed reward preference (doubling delay tolerance). The intervention also reduced craving, ps < 0.05. Thirty days later, n = 18 remained abstinent; importantly, increased future self-similarity persisted. Abstainers' future self-similarity increased following VR. All individual participants showing increased future self-similarity post-VR remained abstinent, and all participants who relapsed showed either reduced or zero effect on future self-similarity. Post-intervention semi-structured interviews revealed emotional engagement with the experience. VR simulation of imagined realities reifies novel clinical interventions that are practicable and personalized. The current study demonstrates an implementation readily applied in the clinic and shows promise for facilitating SUD recovery. Creative collaboration between researchers, clinicians, and VR developers has great potential to revolutionize mental health interventions and expand the range of tools for clinicians targeting SUD and other disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s44192-022-00022-1.

Time to retire the serial Papez circuit: Implications for space, memory, and attention.

After more than 80 years, Papez serial circuit remains a hugely influential concept, initially for emotion, but in more recent decades, for memory. Here, we show how this circuit is anatomically and mechanistically naïve as well as outdated. We argue that a new conceptualisation is necessitated by recent anatomical and functional findings that emphasize the more equal, working partnerships between the anterior thalamic nuclei and the hippocampal formation, along with their neocortical interactions in supporting, episodic memory. Furthermore, despite the importance of the anterior thalamic for mnemonic processing, there is growing evidence that these nuclei support multiple aspects of cognition, only some of which are directly associated with hippocampal function. By viewing the anterior thalamic nuclei as a multifunctional hub, a clearer picture emerges of extra-hippocampal regions supporting memory. The reformulation presented here underlines the need to retire Papez serially processing circuit.

Transvitreal and subretinal fibrinoid reaction following diabetic vitrectomy.

Purpose: To describe an unexpected and atypical transvitreal and subretinal fibrinoid reaction following vitrectomy for non-clearing vitreous hemorrhage due to proliferative diabetic retinopathy. Observations: A 58-year-old woman with bilateral proliferative diabetic retinopathy and non-clearing vitreous hemorrhage underwent combined phacoemulsification, intraocular lens implantation and vitrectomy in the right eye. Two months later she underwent staged phacoemulsification with intraocular lens implantation followed by vitrectomy in the left eye. The early postoperative course of each eye was complicated by choroidal effusion and submacular fibrinoid material on optical coherence tomography. The left eye also developed transvitreal fibrinoid bands. Conclusions and importance: Subretinal fibrin accumulation is a rare complication of diabetic vitrectomy. Optical coherence tomography (OCT) in the early post-operative period may assist in the recognition of this complication.

Is Nerve Electrophysiology a Robust Primary Endpoint in Clinical Trials of Treatments for Diabetic Peripheral Neuropathy?

There is currently no FDA-approved disease-modifying therapy for diabetic peripheral neuropathy (DPN). Nerve conduction velocity (NCV) is an established primary endpoint of disease-modifying therapies in DPN and clinical trials have been powered with an assumed decline of 0.5 m/s/year. This paper sought to establish the time-dependent change in NCV associated with a placebo, compared to that observed in the active intervention group. A literature search identified twenty-one double-blind, randomised controlled trials in DPN of ≥1 year duration conducted between 1971 and 2021. We evaluated changes in neurophysiology, with a focus on peroneal motor and sural sensory NCV and amplitude in the placebo and treatment groups. There was significant variability in the change and direction of change (reduction/increase) in NCV in the placebo arm, as well as variability influenced by the anatomical site of neurophysiological measurement within a given clinical trial. A critical re-evaluation of efficacy trials should consider placebo-adjusted effects and present the placebo-subtracted change in NCV rather than assume a universal annual decline of 0.5 m/s/year. Importantly, endpoints such as corneal confocal microscopy (CCM) have demonstrated early nerve repair, whilst symptoms and NCV have not changed, and should thus be considered as a viable alternative.

The separate and combined properties of the granular (area 29) and dysgranular (area 30) retrosplenial cortex.

Retrosplenial cortex contains two principal subdivisions, area 29 (granular) and area 30 (dysgranular). Their respective anatomical connections in the rat brain reveal that area 29 is the primary recipient of hippocampal and parahippocampal spatial and contextual information while area 30 is the primary interactor with current visual information. Lesion studies and measures of neuronal activity in rodents indicate that retrosplenial cortex helps to integrate space from different perspectives, e.g., egocentric and allocentric, providing landmark and heading cues for navigation and spatial learning. It provides a repository of scene information that, over time, becomes increasingly independent of the hippocampus. These processes, reflect the interactive actions between areas 29 and 30, along with their convergent influences on cortical and thalamic targets. Consequently, despite their differences, both areas 29 and 30 are necessary for an array of spatial and learning problems.

A Direct Comparison of Afferents to the Rat Anterior Thalamic Nuclei and Nucleus Reuniens: Overlapping But Different.

Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI. Despite frequent overlap in layer VI, ventral prefrontal and anterior cingulate inputs to nucleus reuniens were concentrated in the deepest sublayer (VIb). Meanwhile, inputs to the anterior thalamic nuclei originated more evenly from both sublayers VIa and VIb, with the result that they were often located more superficially than the projections to nucleus reuniens. Again, while the many hippocampal (subiculum) neurons projecting to nucleus reuniens and the anterior thalamic nuclei were partially intermingled within the deep cellular parts of the subiculum, cells projecting to nucleus reuniens consistently tended to lie even deeper (i.e., immediately adjacent to the alveus). Variable numbers of double-labeled cells were present in those cortical and subicular portions where the two cell populations intermingled, though they remained in a minority. Our data also show how projections to these two thalamic sites are organized in opposing dorsal/ventral and rostral/caudal gradients across both the cortex and hippocampal formation. While the anterior thalamic nuclei are preferentially innervated by dorsal cortical sites, more ventral frontal sites preferentially reach nucleus reuniens. These anatomic differences may underpin the complementary cognitive functions of these two thalamic areas.

The anterior thalamic nuclei and cognition: A role beyond space?

The anterior thalamic nuclei are a vital node within hippocampal-diencephalic-cingulate circuits that support spatial learning and memory. Reflecting this interconnectivity, the overwhelming focus of research into the cognitive functions of the anterior thalamic nuclei has been spatial processing. However, there is increasing evidence that the functions of the anterior thalamic nuclei extend beyond the spatial realm. This work has highlighted how these nuclei are required for certain classes of temporal discrimination as well as their importance for processing other contextual information; revealing parallels with the non-spatial functions of the hippocampal formation. Yet further work has shown how the anterior thalamic nuclei may be important for other forms of non-spatial learning, including a critical role for these nuclei in attentional mechanisms. This evidence signals the need to reconsider the functions of the anterior thalamic within the framework of their wider connections with sites including the anterior cingulate cortex that subserve non-spatial functions.

Chemogenetics Reveal an Anterior Cingulate-Thalamic Pathway for Attending to Task-Relevant Information.

In a changing environment, organisms need to decide when to select items that resemble previously rewarded stimuli and when it is best to switch to other stimulus types. Here, we used chemogenetic techniques to provide causal evidence that activity in the rodent anterior cingulate cortex and its efferents to the anterior thalamic nuclei modulate the ability to attend to reliable predictors of important outcomes. Rats completed an attentional set-shifting paradigm that first measures the ability to master serial discriminations involving a constant stimulus dimension that reliably predicts reinforcement (intradimensional-shift), followed by the ability to shift attention to a previously irrelevant class of stimuli when reinforcement contingencies change (extradimensional-shift). Chemogenetic disruption of the anterior cingulate cortex (Experiment 1) as well as selective disruption of anterior cingulate efferents to the anterior thalamic nuclei (Experiment 2) impaired intradimensional learning but facilitated 2 sets of extradimensional-shifts. This pattern of results signals the loss of a corticothalamic system for cognitive control that preferentially processes stimuli resembling those previously associated with reward. Previous studies highlight a separate medial prefrontal system that promotes the converse pattern, that is, switching to hitherto inconsistent predictors of reward when contingencies change. Competition between these 2 systems regulates cognitive flexibility and choice.

Distributed interactive brain circuits for object-in-place memory: A place for time?

Rodents will spontaneously learn the location of an individual object, an ability captured by the object-in-place test. This review considers the network of structures supporting this behavioural test, as well as some potential confounds that may affect interpretation. A hierarchical approach is adopted, as we first consider those brain regions necessary for two simpler, 'precursor' tests (object recognition and object location). It is evident that performing the object-in-place test requires an array of areas additional to those required for object recognition or object location. These additional areas include the rodent medial prefrontal cortex and two thalamic nuclei (nucleus reuniens and the medial dorsal nucleus), both densely interconnected with prefrontal areas. Consequently, despite the need for object and location information to be integrated for the object-in-place test, for example, via the hippocampus, other contributions are necessary. These contributions stem from how object-in-place is a test of associative recognition, as none of the individual elements in the test phase are novel. Parallels between the structures required for object-in-place and for recency discriminations, along with a re-examination of the demands of the object-in-place test, signal the integration of temporal information within what is usually regarded as a spatial-object test.

Organisation of cingulum bundle fibres connecting the anterior thalamic nuclei with the rodent anterior cingulate and retrosplenial cortices.

Despite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle. The mouse data were collated from the Allen Mouse Brain Atlas. The projections from the three major anterior thalamic nuclei occupied much of the external medullary stratum of the cingulum bundle, where they were concentrated in its more medial portions. These anterior thalamic projections formed a rostral-reaching basket of efferents prior to joining the cingulum bundle, with anteromedial efferents taking the most rostral routes, often reaching the genu of the corpus callosum, while anterodorsal efferents took the least rostral route. In contrast, the return cortico-anterior thalamic projections frequently crossed directly through the bundle or briefly joined the internal stratum of the cingulum bundle, often entering the internal capsule before reaching the anterior thalamus. These analyses confirm that anterior thalamic connections comprise an important component of the rodent cingulum bundle, while also demonstrating the very different routes used by thalamo-cortical and cortico-thalamic projections. This information reveals how the composition of the cingulum bundle alters along its length.

Deconstructing the Direct Reciprocal Hippocampal-Anterior Thalamic Pathways for Spatial Learning.

The hippocampus is essential for normal memory but does not act in isolation. The anterior thalamic nuclei may represent one vital partner. Using DREADDs, the behavioral consequences of transiently disrupting anterior thalamic function were examined, followed by inactivation of the dorsal subiculum. Next, the anterograde transport of an adeno-associated virus expressing DREADDs was paired with localized intracerebral infusions of a ligand to target specific input pathways. In this way, the direct projections from the anterior thalamic nuclei to the dorsal hippocampal formation were inhibited, followed by separate inhibition of the dorsal subiculum projections to the anterior thalamic nuclei. To assay spatial working memory, all animals performed a reinforced T-maze alternation task, then a more challenging version that nullifies intramaze cues. Across all four experiments, deficits emerged on the spatial alternation task that precluded the use of intramaze cues. Inhibiting dorsal subiculum projections to the anterior thalamic nuclei produced the severest spatial working memory deficit. This deficit revealed the key contribution of dorsal subiculum projections to the anteromedial and anteroventral thalamic nuclei for the processing of allocentric information, projections not associated with head-direction information. The overall pattern of results provides consistent causal evidence of the two-way functional significance of direct hippocampal-anterior thalamic interactions for spatial processing. At the same time, these findings are consistent with hypotheses that these same, reciprocal interactions underlie the common core symptoms of temporal lobe and diencephalic anterograde amnesia.SIGNIFICANCE STATEMENT It has long been conjectured that the anterior thalamic nuclei might be key partners with the hippocampal formation and that, respectively, they are principally responsible for diencephalic and temporal lobe amnesia. However, direct causal evidence for this functional relationship is lacking. Here, we examined the behavioral consequences of transiently silencing the direct reciprocal interconnections between these two brain regions on tests of spatial learning. Disrupting information flow from the hippocampal formation to the anterior thalamic nuclei and vice versa impaired performance on tests of spatial learning. By revealing the conjoint importance of hippocampal-anterior thalamic pathways, these findings help explain why pathology in either the medial diencephalon or the medial temporal lobes can result in profound anterograde amnesic syndromes.

Clinical Utility of Triplicate En Face Image Averaging for Optical Coherence Tomography Angiography in Glaucoma and Glaucoma Suspects.

PRéCIS:: Averaging triplicate en face angiograms of the radial peripapillary capillary (RPC) plexus with optical coherence tomography angiography (OCTA) improves vessel visualization, reduces vessel density parameters, and increases the diagnostic accuracy for glaucoma of one such parameter. PURPOSE: The purpose of this study was to test the hypothesis that triplicate averaging of the RPC layer improves visualization and diagnostic accuracy of OCTA for glaucoma. MATERIALS AND METHODS: This is a cross-sectional study involving 63 primary open-angle glaucoma patients and 70 age-matched glaucoma suspects. Triplicate 6×6 mm OCTA scans of the optic nerve head were acquired, and the RPC layer was extracted. RPC en face images were registered and averaged. Parameters of global entropy, global standard deviation, local texture correlation, local homogeneity, signal-to-noise ratio, and intercapillary distance were used to measure the change in visualization with averaging. Vessel area density (VAD), vessel skeleton density (VSD), and flux parameters were calculated in a 2.8 mm annulus excluding the optic disc. The diagnostic accuracy of these parameters for glaucoma was assessed by calculating the area under the receiver operating curve (AUC) values. RESULTS: Three-frame averaging resulted in decreased global entropy and global standard deviation (Ps<0.001), and increased local texture correlation, local homogeneity, signal-to-noise ratio, and intercapillary distance (Ps<0.001). Averaged images also had reduced VAD, VSD, and flux (Ps<0.001). AUC was significantly increased for VSD after image averaging (P=0.018), while no significant change in AUC was observed for VAD (P=0.229) or flux (P=0.193). CONCLUSIONS: Triplicate averaging improves visualization of the RPC layer and the diagnostic accuracy of VSD for glaucoma. The impact of image averaging on OCTA diagnostic performance and other potential applications warrants further exploration.

Stable Encoding of Visual Cues in the Mouse Retrosplenial Cortex.

The rodent retrosplenial cortex (RSC) functions as an integrative hub for sensory and motor signals, serving roles in both navigation and memory. While RSC is reciprocally connected with the sensory cortex, the form in which sensory information is represented in the RSC and how it interacts with motor feedback is unclear and likely to be critical to computations involved in navigation such as path integration. Here, we used 2-photon cellular imaging of neural activity of putative excitatory (CaMKII expressing) and inhibitory (parvalbumin expressing) neurons to measure visual and locomotion evoked activity in RSC and compare it to primary visual cortex (V1). We observed stimulus position and orientation tuning, and a retinotopic organization. Locomotion modulation of activity of single neurons, both in darkness and light, was more pronounced in RSC than V1, and while locomotion modulation was strongest in RSC parvalbumin-positive neurons, visual-locomotion integration was found to be more supralinear in CaMKII neurons. Longitudinal measurements showed that response properties were stably maintained over many weeks. These data provide evidence for stable representations of visual cues in RSC that are spatially selective. These may provide sensory data to contribute to the formation of memories of spatial information.

Systemic Determinants of Peripapillary Vessel Density in Healthy African Americans: The African American Eye Disease Study.

PURPOSE: To determine the relationship between systemic factors and radial peripapillary capillary (RPC) vessel density (VD) in healthy African American (AA) participants of the African American Eye Disease Study. DESIGN: A population-based, cross-sectional study. METHODS: A total of 4135 eyes from 2127 AA participants aged 40 years and older in Inglewood, California, were imaged for 6×6-mm optic disc scans on a spectral-domain optical coherence tomography angiography (OCTA) device. Of these, 1029 eyes from 1029 participants who met the inclusion and exclusion criteria were analyzed, including only 1 eye per participant. Custom software was used to quantify RPC VD. Multivariate linear regression was used to identify systemic factors associated with RPC VD with a significance level set at 0.05. The contribution of each variable to the final model was estimated with the magnitude of standardized regression coefficients (SRCs). The fit of the final model was measured by R2. RESULTS: The average RPC VD was 0.346±0.045. Controlling for signal strength, the systemic variables in the final multivariate model associated with reduced RPC VD were older age (ß = -0.0123 per decade; SRC = -0.2733; P < .0001), male sex (ß = -0.0067; SRC = -0.0716; P = .0060), and longer diabetes duration (ß = -0.0022 per 5 years; SRC = -0.0527; P = .0427). The model R2 was 0.3689. CONCLUSIONS: Age, sex, and systemic influences, such as diabetes duration, need to be considered when assessing changes in RPC VD in glaucoma and other ocular diseases. Longitudinal studies are needed to investigate whether reduced RPC VD and the factors that affect it are associated with an increased risk of developing glaucomatous nerve damage.

A comparison of density-modulus relationships used in finite element modeling of the shoulder.

Subject- and site-specific modeling techniques greatly improve the accuracy of computational models derived from clinical-resolution quantitative computed tomography (QCT) data. The majority of shoulder finite element (FE) studies use density-modulus relationships developed for alternative anatomical locations. As such, the objectives of this study were to compare the six most commonly used density-modulus relationships in shoulder finite element (FE) studies. To achieve this, ninety-eight (98) virtual trabecular bone cores were extracted from uCT scans of scapulae from 14 cadaveric specimens (7 male; 7 female). Homogeneous tissue moduli of 20 GPa, and heterogeneous tissue moduli scaled by CT-intensity were considered. Micro finite element models (µ-FEMs) of each virtual core were compressively loaded to 0.5% apparent strain and apparent strain energy density (SEDapp) was collected. Each uCT virtual core was then co-registered to clinical QCT images, QCT-FEMs created, and each of the 6 density-modulus relationships applied (6 × 98 = 588 QCT-FEMs). The loading and boundary conditions were replicated and SEDapp was collected and compared to µ-FEM SEDapp. When a homogeneous tissue modulus was considered in the µ-FEMs, SEDapp was best predicted in QCT-FEMs with the density-modulus relationship developed from pooled anatomical locations (QCT-FEM SEDapp = 0.979µ-FEM SEDapp + 0.0066, r2 = 0.933). A different density-modulus relationship best predicted SEDapp (QCT-FEM SEDapp = 1.014µ-FEM SEDapp + 0.0034, r2 = 0.935) when a heterogeneous tissue modulus was considered. This study compared density-modulus relationships used in shoulder FE studies using an independent computational methodology for comparing these relationships.

Reconsidering Strategies for Managing Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: Using Decision Analytics to Find the Optimal Strategy Between One-Stage and Two-Stage Total Knee Revision.

BACKGROUND: Periprosthetic joint infection (PJI) following total knee arthroplasty is a growing concern, as the demand for total knee arthroplasty (TKA) expands annually. Although 2-stage revision is considered the gold standard in management, there is substantial morbidity and mortality associated with this strategy. One-stage revision is associated with lower mortality rates and better quality of life, and there has been increased interest in utilizing the 1-stage strategy. However, surgeons are faced with a difficult decision regarding which strategy to use to treat these infections, considering uncertainty with respect to eradication of infection, quality of life, and societal costs with each strategy. The purpose of the current study was to use decision analysis to determine the optimal decision for the management of PJI following TKA. METHODS: An expected-value decision tree was constructed to estimate the quality-adjusted life-years (QALYs) and costs associated with 1-stage and 2-stage revision. Two decision trees were created: Decision Tree 1 was constructed for all pathogens, and Decision Tree 2 was constructed solely for difficult-to-treat infections, including methicillin-resistant infections. Values for parameters in the decision model, such as mortality rate, reinfection rate, and need for additional surgeries, were derived from the literature. Medical costs were derived from Medicare data. Sensitivity analysis determined which parameters in the decision model had the most influence on the optimal strategy. RESULTS: In both decision trees, the 1-stage strategy produced greater health utility while also being more cost-effective. In the Monte Carlo simulation for Decision Trees 1 and 2, 1-stage was the dominant strategy in about 85% and 69% of the trials, respectively. Sensitivity analysis showed that the reinfection and 1-year mortality rates were the most sensitive parameters influencing the optimal decision. CONCLUSIONS: Despite 2-stage revision being considered the current gold standard for infection eradication in patients with PJI following TKA, the optimal decision that produced the highest quality of life was 1-stage revision. These results should be considered in shared decision-making with patients who experience PJI following TKA. LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Extent of resection predicts risk of progression in adult pilocytic astrocytoma.

Object: Pilocytic astrocytomas are rare tumours in adults. Presentation, management and prognostic factors are poorly characterised. Methods: Retrospective single centre study from 2000 to 2016. Results: 50 cases were identified (median age 29 years; range 16-76). Symptoms at presentation were neurological deficit (n = 21), headache (n = 18) and seizures (n = 6). Five were incidental findings. Five patients had hydrocephalus at presentation and required emergent management, two by endoscopic third ventriculostomy and three by external ventricular drain. Symptoms were present for a median of 16 weeks (range 1 week to 34 years). Surgery consisted of gross total resection (n = 23), subtotal resection (n = 21) or biopsy (n = 6). Progression occurred in 20 patients at a median time of 7 years following surgery and was asymptomatic in just over half of these cases. A greater degree of resection (complete vs. subtotal) was associated with longer time to progression (Kaplan-Meier analysis, log rank test = 3.58, p = 0.059). At their first progression 12 patients underwent re-resective surgery and the remainder received radiotherapy. The median 5-year survival was 80%. Conclusions: In adult patients with a pilocytic astrocytoma, a macroscopic resection should be the aim at the first resective operation. Emergency management of hydrocephalus may be required in the first instance.