Clavicle fixation to reduce short-term analgesia and improve respiratory function in patients with chest wall injuries.

INTRODUCTION: The objective of this study was to determine if operative fixation of clavicle fractures in patients with non-operatively treated ipsilateral rib fractures is associated with a lower overall analgesic requirement and improved respiratory function. MATERIALS AND METHODS: A retrospective matched cohort study was conducted involving patients admitted to a single tertiary trauma centre having sustained a clavicle fracture with ipsilateral rib fracture/s between January 2014 and June 2020. Patients were excluded if brain, abdominal, pelvic, or lower limb trauma was identified. 31 patients with operative clavicle fixation (study group) were matched 1:1 to 31 patients with non-operative management of the clavicle fracture (control group) based on age, sex, number of rib fractures and injury severity score. The primary outcome was the number of analgesic types used, and the secondary outcome was respiratory function. RESULTS: The study group required a mean of 3.50 types of analgesia prior to surgery which decreased to 1.57 post-surgery. The control group required 2.92 types of analgesia, reducing to 1.65 after the date of surgery in the study group. A General Linear Mixed Model indicated that the intervention (operative vs. non-operative management) had statistically significant effects on the number of required analgesic types (p < 0.001, [Formula: see text] = 0.365), oxygen saturation (p = 0.001, [Formula: see text] = 0.341, 95% CI 0.153-0.529) and temporal decline in daily supplemental oxygen requirement (p < 0.001, [Formula: see text] = 0.626, 95% CI 0.455-0.756). CONCLUSION: This study supported the hypothesis that operative clavicle fixation reduces short-term in-patient analgesia use and improves respiratory parameters in patients with ipsilateral rib fractures. LEVEL OF EVIDENCE: Level III therapeutic study.

A systematic review of patient-reported outcome measures used in shoulder instability research.

BACKGROUND: Shoulder instability is extremely common, with various outcome scores used to assess its progression after treatment. This review was performed to identify the scores most commonly used and to evaluate them according to the 4 core domains of shoulder trials (according to the Core Outcome Measures in Effectiveness Trials [COMET] initiative) and their respective psychometric qualities. METHODS: A systematic review of the literature of 3 databases (MEDLINE, Embase, PubMed) was undertaken. Studies were identified using eligibility criteria and critically appraised by 2 authors. Data were extracted using an a priori template. Outcome scores were identified and assessed regarding COMET domain inclusion and their psychometric properties. RESULTS: The most frequently used scores were the Rowe (58%), Constant (33%), Western Ontario Shoulder Instability Index (WOSI; 24%), and American Shoulder and Elbow Surgeons (23%) scores. The majority of outcome scores assessed pain and all assessed physical functioning. Quality of life and a global assessment of treatment success were rarely incorporated. No single outcome score considered all core COMET domains. The WOSI was the most acceptable measure of those assessed with respect to its validity, reliability, and responsiveness. CONCLUSIONS: The WOSI incorporated 3 of the 4 core domains for shoulder trials (pain, physical functioning, and health-related quality of life). It had the most psychometric testing of the identified scores, confirming its reliability, validity, and responsiveness in the setting of shoulder instability. We recommend its use in this setting; however, it should be supplemented with additional outcome scores, such as the University of California-Los Angeles score, to cover all of the core COMET domains.

A profile of health, lifestyle and training habits of 4720 Australian recreational runners-The case for promoting running for health benefits.

ISSUE ADDRESSED: The aim of this study was to characterise lifestyle and training habits of a large cohort of Australian recreational runners. Understanding the health benefits of recreational running and differentiating between the habits of males and females may allow for the development of gender-specific messaging for promoting recreational running as a form of physical activity. METHODS: An online questionnaire was used to collect data from 4720 Australian recreational runners. Data on physical, lifestyle and training characteristics of male and female subgroups were compared using chi-square tests. Multiple logistic regression method was used to assess the effect of running experience on the reported clinically significant weight loss. RESULTS: The study cohort was 54.1% female and 45.9% male. Smoking was uncommon among surveyed runners. The most typical weekly running distance in the cohort was 20-40 km, usually distributed by 2-5 running sessions. Significantly more males than females reported running over 40 km per week (29.9% vs 18.9%, P < .001) and running at least six sessions per week (11.5% vs 6.7%, P < .001). The majority (72.9%) of runners had normal BMI, and the cohort reported a lower overweight/obesity rate than the Australian population. The logistic regression model indicated that commencing running may lead to a clinically significant weight loss irrespectively of sex, participation in other sports and injury history. CONCLUSION: Recreational running was associated with beneficial health outcomes. Commencement of running is associated with weight loss, and regular running supports healthy weight maintenance. Male and female runners had different running preferences which should be taken into account for physical activity promotion. SO WHAT?: Captured health outcomes associated with running and described sex differences in training patterns may assist in development of physical activity promotion programmes involving recreational running, particularly targeting weight loss and healthy weight maintenance.

Prevalence of illness, poor mental health and sleep quality and low energy availability prior to the 2016 Summer Olympic Games.

OBJECTIVE: Establish the prevalence of illness symptoms, poor sleep quality, poor mental health symptoms, low energy availability and stress-recovery state in an Olympic cohort late in the 3 months prior to the Summer Olympic Games. METHODS: Olympic athletes (n=317) from 11 sports were invited to complete questionnaires administered 3 months before the Rio 2016 Olympic Games. These questionnaires included the Depression, Anxiety and Stress Questionnaire, Perceived Stress Scale, Dispositional Resilience Scale, Recovery-Stress Questionnaire (REST-Q-52 item), Low Energy Availability in Females Questionnaire (LEAF-Q), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and custom-made questionnaires on probiotic usage and travel. Multiple illness (case) definitions were applied. ORs and attributable fractions in the population were used. Factor analyses were used to explore the relationships between variables. RESULTS: The response rate was of 42% (male, n=47, age 25.8±4.1 years; female, n=85, age 24.3±3.9 years). Low energy availability was associated with sustaining an illness in the previous month (upper respiratory, OR=3.8, 95% CI 1.2 to 12). The main factor relating to illness pertained to a combination of anxiety and stress-recovery states (as measured by the REST-Q-52 item). All participants reported at least one episode of illness in the last month (100% prevalence). CONCLUSIONS: All participants reported at least one illness symptom in the previous month. Low energy availability was a leading variable associated with illness in Olympic-class athletes. The estimates duration of symptoms ranged from 2 to 7 days. Factor analyses show the interdependence of various health domains and support multidisciplinary care.

The effects of C5aR1 on leukocyte infiltration following pilocarpine-induced status epilepticus.

This study aimed to determine the role C5aR1 plays in mediating immune responses acutely after pilocarpine-induced status epilepticus (SE), specifically those of brain-infiltrating leukocytes. Three days following pilocarpine SE, we determined by flow cytometry the brain immune cell phenotypes and measured key proinflammatory and antiinflammatory cytokine expression by infiltrating leukocytes and microglia in C5aR1-deficient and wild-type mice. Absence of C5aR1 reduced by 47% the numbers of Ly6G+ neutrophils in the brains of No-SE mice and decreased neutrophil entry after SE to levels found in wild-type brains that did not undergo SE (No-SE). Moreover, C5aR1-deficient mice showed increased interleukin (IL)-4 expression in infiltrating leukocytes, but not in microglia. Increases in IL-4 expression in infiltrating leukocytes coupled with decreased neutrophil invasion in C5aR1-deficient mice after SE is likely to contribute to the reduced neuronal loss previously found in these mice compared to their wild-type littermates. Although other SE models need to be investigated to substantiate our findings, this study provides further evidence that C5aR1 is an inflammatory mediator and may play a role in epileptogenesis.

Intravenous immunoglobulin (IVIg) dampens neuronal toll-like receptor-mediated responses in ischemia.

BACKGROUND: Ischemic stroke causes a high rate of deaths and permanent neurological damage in survivors. Ischemic stroke triggers the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1), which activate toll-like receptors (TLRs) and receptor for advanced glycation endproducts (RAGE) in the affected area, leading to an exaggerated inflammatory response and cell death. Both TLRs and RAGE are transmembrane pattern recognition receptors (PRRs) that have been shown to contribute to ischemic stroke-induced brain injury. Intravenous immunoglobulin (IVIg) preparations obtained by fractionating human blood plasma are increasingly being used as an effective therapeutic agent in the treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke has been proposed, but little is known about the direct neuroprotective mechanisms of IVIg. We therefore investigate whether IVIg exerts its beneficial effects on the outcome of neuronal injury by modulating HMGB1-induced TLR and RAGE expressions and activations. METHODS: Primary cortical neurons were subjected to glucose deprivation or oxygen and glucose deprivation conditions and treated with IVIg and recombinant HMGB1. C57/BL6J mice were subjected to middle cerebral artery occlusion, followed by reperfusion, and IVIg was administered intravenously 3 h after the start of reperfusion. Expression of TLRs, RAGE and downstream signalling proteins in neurons and brain tissues were evaluated by immunoblot. RESULTS: Treatment of cultured neurons with IVIg reduced simulated ischemia-induced TLR2, TLR4, TLR8 and RAGE expressions, pro-apoptotic caspase-3 cleavage and phosphorylation of the cell death-associated kinases such as c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) as well as the p65 subunit of nuclear factor kappa B (NF-κB). These results were recapitulated in an in vivo model of stroke. IVIg treatment also upregulated the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) in cortical neurons under ischemic conditions. Finally, IVIg protected neurons against HMGB1-induced neuronal cell death by modulating TLR and RAGE expressions and signalling pathways. CONCLUSIONS: Taken together, these results provide a rationale for the potential use of IVIg to target inappropriately activated components of the innate immune system following ischemic stroke.

Complex alterations in microglial M1/M2 markers during the development of epilepsy in two mouse models.

OBJECTIVE: To characterize the changes in microglial proinflammatory M1 and antiinflammatory M2 marker expression during epileptogenesis in the chronic pilocarpine and intrahippocampal kainate models. METHODS: M1-activated microglia express proinflammatory cytokines driving infiltration of cells, whereas M2-activated microglia are more reparative, promoting phagocytosis of debris and expression of proteins associated with cellular stability and repair. Microglial markers were characterized as acute (3 days after status epilepticus [SE]), early chronic (21 days post-SE), and late chronic epileptic (5-12 months post-SE) time points. Following pilocarpine-SE, microglial markers were assessed by flow cytometry. Quantitative real-time polymerase chain reaction (RT-PCR) was used to measure messenger RNA (mRNA) levels of selected M1 (interleukin [IL] 1ß, tumor necrosis factor α [TNFα] cluster of differentiation [CD],CD16, and CD86), interleukin-6 [IL-6], interleukin-12 [IL-12], Fc receptors 16, and CD86) and M2 (arginase 1 [Arg1], chitinase-3-like protein [Ym1], found in inflammatory zone [FIZZ-1] [FIZZ-1], mannose receptor C type-1 [CD206], interleukin-4 [IL-4], and interleukin-10 (IL-10)) markers in both models. Video-electroencephalography (EEG) recordings were used to quantify late chronic seizure frequency. RESULTS: Three days post-SE microglia in the pilocarpine model expressed M1 and M2 markers, but only M1 markers were upregulated after kainate-induced SE. After 3 weeks, M1/M2 marker expression was largely ablated in the hippocampal formation of both models. Small mRNA level increases of CD11b, glial fibrillary acidic protein (GFAP), and IL-1ß were found in the pilocarpine model, consistent with IL-1ß contributing to spontaneous seizures, whereas mRNA levels of TNFα and Ym1 were decreased. In the late chronic phase, some M1/M2 markers, IL-1ß, TNFα, Arg1, Ym1, and CD206, resurged in the kainate, but not pilocarpine model, which may reflect and/or contribute to highly frequent seizures in kainate-SE mice. SIGNIFICANCE: The common M1 upregulation acutely post-SE may signal a role early in epileptogenesis, with a more pure "inflamed" central nervous system state after kainate-SE, potentially contributing to the development of more frequent seizures. The difference may also be due to the contribution of peripheral inflammation after pilocarpine injection. In summary, the microglial inflammatory response during epileptogenesis is complex, varies between models, and appears to correlate with chronic seizure frequency.

Evidence that collaboration between HIF-1α and Notch-1 promotes neuronal cell death in ischemic stroke.

Recent findings suggest that Notch-1 signaling contributes to neuronal death in ischemic stroke, but the underlying mechanisms are unknown. Hypoxia inducible factor-1α (HIF-1α), a global regulator of cellular responses to hypoxia, can interact with Notch and modulate its signaling during hypoxic stress. Here we show that Notch signaling interacts with the HIF-1α pathway in the process of ischemic neuronal death. We found that a chemical inhibitor of the Notch-activating enzyme, γ-secretase, and a HIF-1α inhibitor, protect cultured cortical neurons against ischemic stress, and combined inhibition of Notch-1 and HIF-1α further decreased neuronal death. HIF-1α and Notch intracellular domain (NICD) are co-expressed in the neuronal nucleus, and co-immunoprecipitated in cultured neurons and in brain tissue from mice subjected to focal ischemic stroke. Overexpression of NICD and HIF-1α in cultured human neural cells enhanced cell death under ischemia-like conditions, and a HIF-1α inhibitor rescued the cells. RNA interference-mediated depletion of endogenous NICD and HIF-1α also decreased cell death under ischemia-like conditions. Finally, mice treated with inhibitors of γ-secretase and HIF-1α exhibited improved outcome after focal ischemic stroke, with combined treatment being superior to individual treatments. Additional findings suggest that the NICD and HIF-1α collaborate to engage pro-inflammatory and apoptotic signaling pathways in stroke.

Functional role of soluble receptor for advanced glycation end products in stroke.

OBJECTIVE: Little is known about the involvement of the soluble form of receptor for advanced glycation end products (sRAGE) in acute ischemic stroke (IS). Here, we aim to identify the role of plasma sRAGE and high mobility group box 1 (HMGB1) in imaging-confirmed IS patients, as well as mice subjected to focal ischemic stroke. METHODS AND RESULTS: IS patients were recruited and plasma samples were collected for the measurement of sRAGE and HMGB1 after stroke. The relation of sRAGE and HMGB1 with acute IS was also investigated in a C57BL/6J mouse model of focal ischemic stroke and primary cortical neurons subjected to oxygen and glucose deprivation. Plasma levels of sRAGE and HMGB1 were both significantly increased within 48 hours after IS, and the sRAGE level was an independent predictor of functional outcome at 3 months poststroke. Immunoprecipitation assays revealed that the binding of plasma HMGB1 to sRAGE increased progressively after IS both in patients and mice. Administration of recombinant sRAGE significantly reduced infiltrating immune cells and improved the outcome of injury in mice, protected cultured neurons against oxygen and glucose deprivation-induced cell death, and ameliorated the detrimental effect of recombinant HMGB1. CONCLUSIONS: Early poststroke plasma sRAGE may play a protective role in IS by capturing HMGB1. Hence, recombinant sRAGE is a potential therapeutic agent in acute IS.

The impact of infection on length of stay in adult burns: A scoping review.

BACKGROUND: The disruption to the immune system and profound metabolic response to burn injury gives rise to a unique susceptibility to infection. Indeed, infection is one of the most frequently encountered post-burns complications placing significant burden on patients and healthcare system. Advancements in burn care have led to marked improvements in burn-related mortality and morbidity; however, scarce hospital resources hamper adequate burn-related care, and patient length of stay (LOS) in hospital is an important drain on such resources. The aim of this review was to assess and evaluate the existing literature relating to the impact of infections on LOS in hospitalised, adult burn patients. METHODS: Electronic searches were performed in Medline and Embase. Eligible studies were those reporting on LOS and infection in adult burn populations. Articles published before 2000 were excluded to ensure that the analysis was focused on contemporary literature that reflects current, clinical management of burn patients. RESULTS: Nineteen studies (54,397 burn patients) were included in the review. All studies were retrospective, with the majority undertaken in North America (14 studies). The mean age range was 38-67 years and the majority of patients were male. Inhalation injury was recorded in eleven studies. The most common types of infection included pneumonia, blood stream infections (BSI) and burn wound infections. Overall, there was a trend towards a positive association between infection and LOS. CONCLUSION: The results of this scoping review provide an overview of the existing literature on the relationship between infection and LOS in adult burn populations. However, significant gaps remain in knowledge which call for further high-quality research. Standardised definitions for the collection of infection data and the use of burns specific infection control guidelines are also critical to understanding and improving patient outcomes.

Clinical Outcomes of Arthroscopic Ligament-Sparing Dorsal Capsulodesis for Partial Scapholunate Ligament Tear.

Introduction Various wrist arthroscopy techniques can be used in the management of scapholunate ligament (SLL) partial tears but their success has not been proven. Arthroscopic techniques including thermal shrinkage are becoming more popular in the management of partial SLL injuries. We hypothesized that arthroscopic ligament-sparing capsular tightening yields reliable and satisfactory results for the management of partial SLL tears. Methods A prospective cohort study was conducted on adult (age ≥18 years) patients with chronic partial SLL tears. All patients failed a trial of conservative management consisting of scapholunate strengthening exercises. Patients underwent an arthroscopic dorsal capsular tightening of the radiocarpal joint capsule radial to the origin of the dorsal radiocarpal ligament and proximal to the dorsal intercarpal ligament by either thermal shrinkage or dorsal capsule abrasion. Demographic data, radiological outcomes, patient-rated outcome measures and objective measures of wrist range of motion (ROM), and grip and pinch strength were recorded. Postoperative outcome scores were collected at 3, 6, 12, and 24 months. Data are reported as median and interquartile range, and comparisons were drawn between baseline and last follow-up. Clinical outcome data were analyzed using a linear mixed model method, while radiographic outcomes were assessed with nonparametric analysis with p < 0.05 indicating statistical significance. Results Twenty-three wrists (22 patients) underwent SLL treatment by thermal capsular shrinkage (19 wrists) or dorsal capsular abrasion (4 wrists). Median age at surgery was 41 years (range: 32-48) and median follow-up time was 12 months (range: 3-24). Pain significantly decreased from 62 (45-76) to 18 (7-41) and satisfaction significantly increased from 2 (0-24) to 86 (52-92). Patient-Rated Wrist and Hand Evaluation and Quick Disabilities of the Arm, Shoulder, and Hand significantly improved from 68 (38-78) to 34 (13-49) and from 48 (27-55) to 36 (4-58), respectively. Median grip and tip pinch strength significantly increased at final review. Range of movement and lateral pinch strength were satisfactory and maintained. Four patients required further surgery for ongoing pain or reinjury. All were successfully managed with partial wrist fusion or wrist denervation. Conclusion Arthroscopic ligament-sparing dorsal capsular tightening is a safe and effective treatment for partial SLL tears. Dorsal capsular tightening demonstrates good pain relief and patient satisfaction while improving patient-reported outcomes, grip strength, and maintaining ROM. Longer term studies are required to determine the longevity of these results.

Factors associated with higher alcohol concentrations in emergency department presentations: PACE study.

INTRODUCTION: The health impact from alcohol is of recognised concern, from acute intoxication as well as increased risk of chronic health issues over time. Identifying factors associated with higher alcohol consumption when presenting to the emergency department (ED) will inform public health policy and enable more targeted health care and appropriate referrals. METHODS: Secondary testing of blood samples collected during routine clinical care of 1160 ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, for 10 days between 22 January and 1 February 2021. Alcohol was measured by blood ethanol (intake in recent hours) and phosphatidylethanol (PEth; intake over 2-4 weeks). Zero-inflated negative binomial regression was used to identify demographic and clinical factors associated with higher alcohol concentrations. RESULTS: Males were found to have 83% higher blood ethanol and 32% higher PEth concentrations than females (adjusted rate ratio [ARR] 1.83, 95% confidence interval [CI] 1.37-2.45 and ARR 1.32, 95% CI 1.04-1.68, respectively). Blood ethanol concentrations were 3.4 times higher for those 18-44 years, compared to those aged 65+ (ARR 3.40, 95% CI 2.40-4.82) whereas PEth concentrations were found to be the highest in those aged 45-64 years, being 70% higher than those aged 65+ (ARR 1.70, 95% CI 1.19-2.44). Patients brought in involuntarily had eight-times higher blood ethanol concentrations than those who self-attended. DISCUSSION AND CONCLUSIONS: This study used two alcohol markers to identify factors associated with higher alcohol concentrations in emergency presentations. The findings demonstrate how these biomarkers can provide informative data for public health responses and monitoring of alcohol use trends.

Prevalence of alcohol consumption in emergency presentations: Novel approach using two biomarkers, ethanol and phosphatidylethanol.

INTRODUCTION: The aim was to determine the prevalence of alcohol-related presentations to an emergency department (ED) in a major Australian hospital, through a novel surveillance approach using two biomarkers, blood ethanol and phosphatidylethanol (PEth). METHODS: Observational study using secondary testing of blood samples collected during routine clinical care of ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, between 22 January and 2 February 2021. Data were collected from 1160 patients during the 10-day study period. The main outcomes were the prevalence of acute alcohol intake, as determined by blood ethanol, and recent use over 2-4 weeks, as determined by PEth concentrations, for all ED presentations and different diagnostic groups. RESULTS: The overall prevalence for blood ethanol was 9.3% (95% confidence interval [CI] 7.8%, 11.1%), 5.3% for general medical presentations, increasing four-fold to 22.2% for injury presentations. The overall prevalence of PEth positive samples was 32.5% (95% CI 29.9%, 35.3%) and 41.4% for injury presentations. There were 263 (25.3%) cases that tested negative for acute blood ethanol but positive for PEth concentrations indicative of significant to heavy medium-term alcohol consumption. DISCUSSION AND CONCLUSIONS: This novel surveillance approach demonstrates that using blood ethanol tests in isolation significantly underestimates the prevalence of medium-term alcohol consumption in ED presentations. Prevalence of alcohol use was higher for key diagnostic groups such as injury presentations. Performing periodic measurement of both acute and medium-term alcohol consumption accurately and objectively in ED presentations, would be valuable for informing targeted public health prevention and control strategies.

PREdiction and Diagnosis using Imaging and Clinical biomarkers Trial in Traumatic Brain Injury (PREDICT-TBI) study protocol: an observational, prospective, multicentre cohort study for the prediction of outcome in moderate-to-severe TBI.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition with a broad spectrum of injury severity, pathophysiological processes and variable outcomes. For moderate-to-severe TBI survivors, recovery is often protracted and outcomes can range from total dependence to full recovery. Despite advances in medical treatment options, prognosis remains largely unchanged. The objective of this study is to develop a machine learning predictive model for neurological outcomes at 6 months in patients with a moderate-to-severe TBI, incorporating longitudinal clinical, multimodal neuroimaging and blood biomarker predictor variables. METHODS AND ANALYSIS: A prospective, observational, cohort study will enrol 300 patients with moderate-to-severe TBI from seven Australian hospitals over 3 years. Candidate predictors including demographic and general health variables, and longitudinal clinical, neuroimaging (CT and MRI), blood biomarker and patient-reported outcome measures will be collected at multiple time points within the acute phase of injury. The predictor variables will populate novel machine learning models to predict the Glasgow Outcome Scale Extended 6 months after injury. The study will also expand on current prognostic models by including novel blood biomarkers (circulating cell-free DNA), and the results of quantitative neuroimaging such as Quantitative Susceptibility Mapping and Dynamic Contrast Enhanced MRI as predictor variables. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Royal Brisbane and Women's Hospital Human Research Ethics Committee, Queensland. Participants or their substitute decision-maker/s will receive oral and written information about the study before providing written informed consent. Study findings will be disseminated by peer-review publications and presented at national and international conferences and clinical networks. TRIAL REGISTRATION NUMBER: ACTRN12620001360909.

Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways.

Intravenous immunoglobulin (IVIg) preparations obtained by fractionating blood plasma, are increasingly being used increasingly as an effective therapeutic agent in treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke and Alzheimer's disease has been proposed, but little is known about the neuroprotective mechanisms of IVIg. In this study, we investigated the effect of IVIg on downstream signaling pathways that are involved in neuronal cell death in experimental models of stroke and Alzheimer's disease. Treatment of cultured neurons with IVIg reduced simulated ischemia- and amyloid ßpeptide (Aß)-induced caspase 3 cleavage, and phosphorylation of the cell death-associated kinases p38MAPK, c-Jun NH2 -terminal kinase and p65, in vitro. Additionally, Aß-induced accumulation of the lipid peroxidation product 4-hydroxynonenal was attenuated in neurons treated with IVIg. IVIg treatment also up-regulated the anti-apoptotic protein, Bcl2 in cortical neurons under ischemia-like conditions and exposure to Aß. Treatment of mice with IVIg reduced neuronal cell loss, apoptosis and infarct size, and improved functional outcome in a model of focal ischemic stroke. Together, these results indicate that IVIg acts directly on neurons to protect them against ischemic stroke and Aß-induced neuronal apoptosis by inhibiting cell death pathways and by elevating levels of the anti-apoptotic protein Bcl2.

Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.

The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRgamma was essential for macrophage activation and Th17 adjuvanticity. The FcRgamma-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRgamma were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guérin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.

Characteristics and Effectiveness of Postoperative Rehabilitation Strategies in Ankle Fractures: A Systematic Review.

OBJECTIVES: To explore the characteristics and to report on the effectiveness of postoperative rehabilitation strategies for people with an ankle fracture. DATA SOURCES: PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL were searched to identify studies published from January 2010 to November 2021. STUDY SELECTION: Studies that described or evaluated postoperative rehabilitation strategies for surgically repaired ankle fractures were included. DATA EXTRACTION: Data on postoperative rehabilitation were extracted in accordance with the Template for Intervention Description and Replication guide. Quality was assessed using the National Heart, Lung, and Blood Institute's Study Quality Assessment Tools. DATA SYNTHESIS: Meta-analysis was planned to look at the effectiveness of postoperative rehabilitation strategies. Forty studies described postoperative rehabilitation strategies without evaluating effectiveness, whereas 15 studies focused on evaluating effectiveness. Because of the large variety in postoperative strategies and outcomes, narrative synthesis was deemed most suitable to answer our aims. Characteristics of postoperative rehabilitation strategies varied widely and were poorly described in a way that could not be replicated. Most of the studies (48%) used a late weight-bearing approach, although definitions and details around weight-bearing were unclear. CONCLUSIONS: Late weight-bearing has been the most common postoperative approach reported in the past 10 years. The variety of definitions around weight-bearing and the lack of details of rehabilitation regimens limit replication and affect current clinical practice. The authors propose to adopt consistent definitions and terminology around postoperative practices such as weight-bearing to improve evidence for effectiveness and ultimately patient outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Prevalence of Alcohol Consumption in Emergency department presentations (PACE) in Queensland, Australia, using alcohol biomarkers ethanol and phosphatidylethanol: an observational study protocol.

INTRODUCTION: Alcohol use in patients presenting to the emergency department (ED) is a significant problem in many countries. There is a need for valid and reliable surveillance of the prevalence of alcohol use in patients presenting to the ED, to provide a more complete picture of the risk factors and inform targeted public health interventions. This PACE study will use two biomarkers, blood ethanol and phosphatidylethanol (PEth), to determine the patterns, presence and level of alcohol use in patients presenting to an Australian ED. METHODS AND ANALYSIS: This is an observational prevalence study involving the secondary use of routinely collected blood samples from patients presenting to the Royal Brisbane and Women's Hospital (RBWH) Emergency and Trauma Centre (ETC). Samples will be tested for acute and medium-term alcohol intake using the two biomarkers blood ethanol and PEth respectively, over one collection period of 10-12 days. Descriptive statistics such as frequencies, percentages, means, SD, medians and IQRs, will be used to describe the prevalence, pattern and distribution of acute and medium-term alcohol intake in the study sample. The correlation between acute and medium-term alcohol intake levels will also be examined. ETHICS AND DISSEMINATION: This study has been approved by the RBWH Human Research Ethics Committee (reference, LNR/2019/QRBW/56859). Findings will be disseminated to key stakeholders such as RBWH ETC, Australasian College for Emergency Medicine, Royal Australasian College of Surgeons, Statewide Clinical Networks, and used to inform clinicians and hospital services. Findings will be submitted for publication in peer-reviewed journals and presentation at appropriate conferences.

Correlation of magnetic resonance and arthroscopy in the diagnosis of shoulder injury.

BACKGROUND: Advances in shoulder magnetic resonance imaging (MRI) and arthrography (MRA) have revolutionised musculoskeletal diagnosis and surgical planning. Despite this, the overall accuracy of MRI, with or without intra-articular contrast, can be variable. METHODS: In this prospective non-randomised analysis, 200 participants (74.5% males) with suspected shoulder injuries underwent MRI (41.0%) or MRA followed by arthroscopy. A study specific proforma was developed to ensure consistency of reporting by radiologists and surgeons. The reports were compared to assess the predictive power of MRI/MRA. Specific assessment of rotator cuff tendon appearance, long head of biceps (LHB) tendon appearance, position and anchor, subacromial space, glenoid labrum and humeral cartilage grade were included. RESULTS: Shoulder MRA demonstrated a higher agreement with arthroscopy than MRI for supraspinatus, infraspinatus and subscapularis tendon appearance (κ = 0.77 vs. κ = 0.61, κ = 0.55 vs. κ = 0.53 and κ = 0.58 vs. κ = 0.46 respectively). There were also superior agreement rates with MRA compared to MRI for LHB tendon appearance (κ = 0.70 vs. κ =0.54) and position (κ = 0.89 vs. κ = 0.72). As an overall assessor of shoulder pathology we found significantly higher total agreement scores when MRA was used (p = 0.002). DISCUSSION: Whilst magnetic resonance imaging with arthrography is an extremely useful tool to assess underlying pathological shoulder states it does not confer 100% accuracy. In cases whereby this modality is inconclusive, an examination under anaesthesia and diagnostic arthroscopic assessment for the detection of intra-articular shoulder pathology may be considered.