A Prospective Cohort Study Characterizing Incidence of Dural Venous Sinus Thrombosis in Traumatic Brain Injury Patients with Skull Fractures.

BACKGROUND: Limited retrospective data suggest that dural venous sinus thrombosis (DVST) in traumatic brain injury (TBI) patients with skull fractures is common and associated with significant morbidity and mortality. Prospective data accurately characterizing the incidence of DVST in patients with high-risk TBI are sparse but are needed to develop evidence-based TBI management guidelines. METHODS: After obtaining institutional approval, 36 adult patients with TBI with skull fractures admitted to an Australian level III adult intensive care unit between April 2022 and January 2023 were prospectively recruited and underwent computed tomography venography or magnetic resonance venography within 72 hours of injury. When available, daily maximum intracranial pressure was recorded. RESULTS: Dural venous sinus abnormality was common (36.1%, 95% confidence interval 22.5%-52.4%) and strongly associated with DVST (P = 0.003). The incidence of DVST was 13.9% (95% confidence interval 6.1%-28.7%), which was lower than incidence reported in previous retrospective studies. Of DVSTs confirmed by computed tomography venography, 80% occurred in patients with extensive skull fractures including temporal or parietal bone fractures in conjunction with occipital bone fractures (P = 0.006). However, dural venous sinus abnormality and DVST were not associated with an increase in maximum daily intracranial pressure within the first 7 days after injury. CONCLUSIONS: Dural venous sinus abnormality was common in TBI patients with skull fractures requiring intensive care unit admission. DVST was confirmed in more than one third of these patients, especially patients with concomitant temporal or parietal and occipital bone fractures. Computed tomography venography is recommended for this subgroup of TBI patients.

Monitoring anti-Xa Levels to Optimize Low-Molecular-Weight-Heparin Thromboprophylaxis in High-Risk Hospitalized Patients: A Stratified Meta-Analysis.

It is uncertain whether monitoring or targeting anti-Xa levels is necessary when using low-molecular-weight-heparin (LMWH) to prevent venous thromboembolism (VTE). This stratified meta-analysis assessed whether monitoring trough or peak anti-Xa levels with LMWH dosing would reduce risk of VTE. Twelve non-randomized studies involving 3604 hospitalized patients met the inclusion criteria and were subject to meta-analysis. Eight studies assessed the association between VTE and peak anti-Xa levels (between .2 and .5 IU/ml) and four studies assessed the benefits of targeting the trough anti-Xa levels (>.1 IU/ml). Achieving an adequate peak or trough anti-Xa level was associated with a reduced risk of VTE (random-effects model odds ratio [OR] .52, 95% confidence interval [CI] .34-.77; P = .001, I2 = 30% and P-value for heterogeneity = .171) compared with using a fixed standard dose of LMWH. Targeting the trough level (OR .40, 95%CI 0.22-.75, P = .004) appeared to be more effective than targeting the peak level (OR .62, 95%CI 0.37-1.03, P = .066), although a formal interaction analysis did not confirm they were statistically different (ratio of ORs = 1.52, 95%CI 0.68-3.40; z score = 1.03, P = .306). Targeting a higher anti-Xa level did not appear to increase the risk of bleeding or transfusion (OR 1.20, 95%CI 0.46-3.17, P = .707).

Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage: A systematic review of published prediction models with risk of bias and clinical applicability assessment.

BACKGROUND: Pre-treatment rebleeding following aneurysmal subarachnoid hemorrhage (aSAH) increases the risk of death and a poor neurological outcome. Current guidelines recommend aneurysm treatment "as early as feasible after presentation, preferably within 24 h of onset" to mitigate this risk, a practice termed ultra-early treatment. However, ongoing debate regarding whether ultra-early treatment is independently associated with reduced re-bleeding risk, together with the recognition that re-bleeding occurs even in centres practicing ultra-early treatment due to the presence of other risk-factors has resulted in a renewed need for patient-specific re-bleed risk prediction. Here, we systematically review models which seek to provide patient specific predictions of pre-treatment rebleeding risk. METHODS: Following registration on the International prospective register of systematic reviews (PROSPERO) CRD 42023421235; Ovid Medline (Pubmed), Embase and Googlescholar were searched for English language studies between 1st May 2002 and 1st June 2023 describing pre-treatment rebleed prediction models following aSAH in adults ≥18 years. Of 763 unique records, 17 full texts were scrutinised with 5 publications describing 4 models reviewed. We used the semi-automated template of Fernandez-Felix et al. incorporating the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for data extraction, risk of bias and clinical applicability assessment. To further standardize risk of bias and clinical applicability assessment, we also used the published explanatory notes for the PROBAST tool and compared the aneurysm treatment practices each prediction model's formulation cohort experienced to a prespecified benchmark representative of contemporary aneurysm treatment practices as outlined in recent evidence-based guidelines and published practice pattern reports from four developed countries. RESULTS: Reported model discriminative performance varied between 0.77 and 0.939, however, no single model demonstrated a consistently low risk of bias and low concern for clinical applicability in all domains. Only the score of Darkwah Oppong et al. was formulated using a patient cohort in which the majority of patients were managed in accordance with contemporary, evidence-based aneurysm treatment practices defined by ultra-early and predominantly endovascular treatment. However, this model did not undergo calibration or clinical utility analysis and when applied to an external cohort, its discriminative performance was substantially lower that reported at formulation. CONCLUSIONS: No existing prediction model can be recommended for clinical use in centers practicing contemporary, evidence-based aneurysm treatment. There is a pressing need for improved prediction models to estimate and minimize pre-treatment re-bleeding risk.

Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that' s the question.

The aging population is an important issue around the world especially in developed countries. Although medical advances have substantially extended life span, the same cannot be said for the duration of health span. We are seeing increasing numbers of elderly people who are frail and/or have multiple chronic conditions; all of these can affect the quality of life of the elderly population as well as increase the burden on the healthcare system. Aging is mechanistically related to common medical conditions such as diabetes mellitus, ischemic heart disease, cognitive decline, and frailty. A recently accepted concept termed 'Accelerated Biological Aging' can be diagnosed when a person's biological age-as measured by biomarkers of DNA methylation-is older than their corresponding chronological age. Taurine, a conditionally essential amino acid, has received much attention in the past few years. A substantial number of animal studies have provided a strong scientific foundation suggesting that this amino acid can improve cellular and metabolic health, including blood glucose control, so much that it has been labelled one of the 'longevity amino acids'. In this review article, we propose the rationale that an adequately powered randomized-controlled-trial (RCT) is needed to confirm whether taurine can meaningfully improve metabolic and microbiome health, and biological age. This trial should incorporate certain elements in order to provide the much-needed evidence to guide doctors, and also the community at large, to determine whether this promising and inexpensive amino acid is useful in improving human metabolic health.

Sex-related differences in functional capacity and its implications in risk stratification before major non-cardiac surgery: a post hoc analysis of the international METS study.

Background: Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO2), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a post hoc analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO2 improve risk prediction of postoperative complications. Methods: We undertook a post hoc analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n = 1266). Logistic regression models were analyzed for the association of low peak VO2 with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO2 thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO2 threshold (14 mL kg-1 min-1) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI). Findings: Female patients (n = 480) had a lower mean (SD) peak VO2 than males (16.7 (4.9) mL kg-1 min-1 versus 21.2 (6.5) mL kg-1 min-1, p < 0.001) and a lower postoperative complication rate (10.4% versus 15.3%; p = 0.018) than males (n = 786). The optimal peak VO2 threshold for predicting postoperative complications was 12.4 mL kg-1 min-1 for females and 22.3 mL kg-1 min-1 for males, respectively. In the multivariable regression model, low non-sex-specific peak VO2 did not independently predict postoperative complications. In contrast, low sex-specific peak VO2 was an independent predictor of postoperative complications (OR 2.29; 95% CI: 1.60, 3.30; p < 0.001). The optimism-corrected AUC-ROC of the sex-specific model was higher compared with the non-sex-specific model (0.73 versus 0.7; DeLong's test: p = 0.021). The sex-specific model classified 39% of the patients more correctly than the baseline model (NRI = 0.39; 95% CI: 0.24, 0.55). In contrast, the non-sex-specific model only classified 9% of the patients more correctly when compared against the baseline model (NRI = 0.09; 95% CI: -0.04, 0.22). Interpretation: Our data report sex-specific differences in preoperative CPET-derived functional capacity parameters. Sex-specific peak VO2 thresholds identify patients at increased risk for postoperative complications with a higher discriminatory ability than a sex-unspecific threshold. As such, sex-specific threshold values should be considered in preoperative CPET to potentially improve risk stratification and to guide surgical decision-making, including eligibility for surgery, preoperative optimization strategies (prehabilitation) or seeking non-surgical options. Funding: There was no funding for the present study. The original METS study was funded by Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Dose-related relationship between ergothioneine concentrations and risk of preeclampsia.

The study by Kenny et al. is of considerable importance. They concluded that there was a weak association between the ergothioneine levels and maternal age, and if a threshold was set at the 90th percentile of the reference range in the control population (≥462 ng/ml), only one of these 97 women (1%) developed preeclampsia, versus 96/397 (24.2%) whose ergothioneine level was below this threshold. These results suggest that there might be a dichotomized association between ergothioneine concentrations and preeclampsia; and only a high ergothioneine level over 90th percentile of the control population could be protective against preeclampsia. With the kind supply of the dataset from the authors, further analysis using univariable as well as multivariable analyses were performed while allowing for non-linearity between ergothioneine concentrations and risk of preeclampsia using a 3-knot restricted cubic spline function. The univariable results showed that ergothioneine had a significant non-linear association with preeclampsia and it would start to offer protective effect from 300 ng/ml onward. The results were similar to the multivariable analysis. In addition, the analysis also confirmed that body mass index was significantly associated with an increased risk of preeclampsia.

Biological age as a predictor of unplanned intensive care readmission during the same hospitalization.

BACKGROUND: Biological age is increasingly being recognized as an important predictor of health but its utility in acute care setting remains uncertain. OBJECTIVE: We assessed whether biological age on intensive care unit (ICU) admission can predict unplanned ICU readmission during the same hospitalization. METHODS: The Levine PhenoAge model based on biomarkers of DNA methylation was used to determine each patient's biological age. The difference between PhenoAge and chronological age was indexed to the local context by regressing PhenoAge on chronological age using linear regression. A positive residual implied one's biological age was older than the corresponding chronological age compared to other patients - defined as PhenoAgeAccel. RESULTS: Of the 2950 patients included, 153 (5.2%) had unplanned ICU readmission. Chronological age, Acute Physiology and Chronic Health Evaluation II score, the use of mechanical ventilation, vasopressor, or renal replacement therapy were not significantly different between those with and without readmission. PhenoAgeAccel was, however, more common among those who had unplanned ICU readmission (52% vs 43%, p =0.031). Quantitatively, the degree of phenotypical age above chronological age exhibited a 'dose-related' relationship with the risk of readmission (odds ratio 1.12, 95% confidence interval 1.01-1.24; p=0.040) after adjusting for chronological age, comorbidities, and severity of acute illness in the index (first) ICU admission. CONCLUSION: Biological age was predictive of unplanned ICU readmission during the same hospitalization.

Biological age is superior to chronological age in predicting hospital mortality of the critically ill.

Biological age is increasingly recognized as being more accurate than chronological age in determining chronic health outcomes. This study assessed whether biological age, assessed on intensive care unit (ICU) admission, can predict hospital mortality. This retrospective cohort study, conducted in a tertiary multidisciplinary ICU in Western Australia, used the Levine PhenoAge model to estimate each patient's biological age (also called PhenoAge). Each patient's PhenoAge was calibrated to generate a regression residual which was equivalent to biological age unexplained by chronological age in the local context. PhenoAgeAccel was a dichotomized measure of the residuals, and its presence suggested that one was biologically older than the corresponding chronological age. Of the 2950 critically ill adult patients analyzed, 291 died (9.9%) before hospital discharge. Both PhenoAge and its residuals (after regressing on chronological age) had a significantly better ability to differentiate between hospital survivors and non-survivors than chronological age (area under the receiver-operating-characteristic curve 0.648 and 0.654 vs. 0.547 respectively). Being phenotypically older than one's chronological age was associated with an increased risk of mortality (PhenoAgeAccel hazard ratio [HR] 1.997, 95% confidence interval [CI] 1.568-2.542; p = 0.001) in a dose-related fashion and did not reach a plateau until at least a 20-year gap. This adverse association remained significant (adjusted HR 1.386, 95% CI 1.077-1.784; p = 0.011) after adjusted for severity of acute illness and comorbidities. PhenoAgeAccel was more prevalent among those with pre-existing chronic cardiovascular disease, end-stage renal failure, cirrhosis, immune disease, diabetes mellitus, or those treated with immunosuppressive therapy. Being phenotypically older than one's chronological age was more common among those with comorbidities, and this was associated with an increased risk of mortality in a dose-related fashion in the critically ill that was not fully explained by comorbidities and severity of acute illness.

Incidence of factor XII deficiency in critically ill patients with a prolonged activated partial thromboplastin time: a prospective observational study.

Limited data is available on factor XII deficiency in critically ill patients with prolonged activated partial thromboplastin time (aPTT). The association of factor XII deficiency with an increased risk of thromboembolism is unclear. This prospective observational study assessed the incidence of factor XII deficiency among critically ill patients with prolonged aPTT (>40 s), whether factor XII deficiency manifesting as prolonged aPTT was associated with an increased risk of thromboembolism, and clotting time on a viscoelastic (ROTEM) test was useful to predict factor XII deficiency. Of the 40 included patients, 48% [95% confidence interval (CI) 33-63) had a factor XII deficiency (mean ±â€Šstandard deviation of factor XII level of all patients: 54% ±â€Š29%). Factor XII levels were not significantly correlated with the measured aPTT ( r  = -0.163, P  = 0.315). Factor XII deficiency was significantly more common in patients who were less critically ill ( P  = 0.027), but it was not significantly related to Disseminated Intravascular Coagulation scores ( P  = 0.567). The incidence of symptomatic venous thromboembolism ( P  = 0.246), allogeneic blood transfusion ( P  = 0.816), and hospital mortality ( P  = 0.201) were not significantly different between those with and without factor XII deficiency. The clotting time on the viscoelastic test was not predictive of factor XII deficiency (area under the receiver-operating characteristic = 0.605, P  = 0.264). Factor XII deficiency was common in critically ill patients with a prolonged aPTT. There was no association between factor XII deficiency and risk of thromboembolism. The clotting time on ROTEM was not predictive of the presence of factor XII deficiency.

The association between intraoperative cardiopulmonary bypass power and complications after cardiac surgery.

BACKGROUND: Low cardiac power (product of flow and pressure) has been shown to be associated with mortality in patients with cardiogenic shock after acute myocardial infarction, but has not been studied in cardiac surgical patients. This study's hypothesis was that cardiac power during cardiopulmonary bypass for cardiac surgery would have a greater association with adverse events than either flow or MAP (mean arterial pressure) alone. METHODS: We undertook a retrospective observational study using patient data from February 2015 to March 2022 undergoing cardiac surgery at Fiona Stanley Hospital in Perth Australia. Excluded were patient age less than 18 years old, patients undergoing thoracic transplantation, ventricular assist devices, off pump cardiac surgery and aortic surgery. The primary outcome was a composite outcome of 30-days mortality, stroke or new-onset renal insufficiency. RESULTS: Overall, 1984 cardiac surgeries were included in the analysis. Neither duration nor area below thresholds tested for power, MAP or flow was associated with the primary composite outcome. However, we found that an area below MAP thresholds 35-50 mmHg was associated with new renal insufficiency (adjusted odds ratio 1.17 [95% CI 1.02 to 1.35] for patients spending 10 min at 10 mmHg below 50 mmHg MAP compared to those who did not). CONCLUSIONS: This study suggests that MAP during cardiopulmonary bypass, but not power or flow, was an independent risk factor for adverse renal outcomes for cardiac surgical patients.

Rebleeding following aneurysmal subarachnoid hemorrhage before 'endovascular first' treatment: a retrospective case-control study of published scoring systems.

BACKGROUND: Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage (aSAH) affects up to 7.2% of patients even with ultra-early treatment within 24 hours. We retrospectively compared the utility of three published re-bleed prediction models and individual predictors between cases who re-bled matched to controls using size and parent vessel location from a cohort of patients treated in an ultra-early, 'endovascular first' manner. METHODS: On retrospective analysis of our 9-year cohort of 707 patients suffering 710 episodes of aSAH, there were 53 episodes of pre-treatment re-bleeding (7.5%). Forty-seven cases who had a single culprit aneurysm were matched to 141 controls. Demographic, clinical and radiological data were extracted and predictive scores calculated. Univariate, multivariate, area under the receiver operator characteristic curve (AUROCC) and Kaplan-Meier (KM) survival curve analyses were performed. RESULTS: The majority of patients (84%) were treated using endovascular techniques at a median 14.5 hours post-diagnosis. On AUROCC analysis the score of Liu et al. had minimal utility (C-statistic 0.553, 95% confidence interval (CI) 0.463 to 0.643) while the risk score of Oppong et al. (C-statistic 0.645 95% CI 0.558 to 0.732) and the ARISE-extended score of van Lieshout et al. (C-statistic 0.53 95% CI 0.562 to 0.744) had moderate utility. On multivariate modeling, the World Federation of Neurosurgical Societies (WFNS) grade was the most parsimonious predictor of re-bleeding (C-statistic 0.740, 95% CI 0.664 to 0.816). CONCLUSIONS: For aSAH patients treated in an ultra-early timeframe matched on size and parent vessel location, WFNS grade was superior to three published models for re-bleed prediction. Future re-bleed prediction models should incorporate the WFNS grade.

Correct dosing of Prothrombinex-VF in normalising elevated international normalised ratio in critically ill patients: a prospective cohort pilot study.

BACKGROUND: Prothrombinex-VF is being increasingly used as an off-label therapy to correct non-warfarin-related elevations in international normalised ratio (INR) in the critically ill. Currently there are no dosing guidelines for such use. AIMS: To validate a prediction equation, embedded in a smartphone application (app), to guide dosing of Prothrombinex-VF in critically ill patients. METHODS: A prospective pilot cohort study of critically ill adult patients with elevated INRs who were treated with Prothrombinex-VF. The main outcome measured was INR following Prothrombinex-VF administration. RESULTS: Of the 31 patients included, five (16%) were taking warfarin prior to admission and 14 (45%) had chronic liver disease. There was a significant decrease in INR after Prothrombinex-VF treatment (P < 0.001) and a significant correlation between the app's predicted INRs and the measured INRs (r = 0.63 and P < 0.001). The app's predicted INRs were less accurate for patients with chronic liver disease than for those without. Overall, the app's recommendations achieved an INR either similar to (29.6%) or better than (55.6%) what would have been achieved had the warfarin reversal guidelines been applied to dose the Prothrombinex-VF. CONCLUSION: The app appeared to be reasonably accurate at predicting normalisation of elevated INRs after administration of Prothrombinex-VF, especially among patients without liver disease. Its dosing recommendations were similar to or possibly better than preexisting warfarin reversal guidelines in over 85% of the situations analysed, if we assume a higher dose of Prothrombinex-VF would achieve a greater reduction in INR than a lower dose.

Utility of the National Emergency Laparotomy Audit prognostic model in predicting outcomes in an Australian health system.

The Royal College of Anaesthetists was commissioned by the United Kingdom Health Quality Partnership to conduct the National Emergency Laparotomy Audit of England and Wales (NELA), to compare outcomes of patients undergoing emergency laparotomy in order to promote quality improvement. Prior to 2016 there were minimal data for emergency laparotomy patients in Australia. The aim of this cohort study was to assess the utility and applicability of the NELA model in a tertiary centre in Western Australia. NELA-related data of patients who underwent emergency laparotomy, between June 2018 and May 2020, were merged with other administrative databases and clinical records. The discriminative ability and calibration of the model were assessed by the area under the receiver operating characteristic (AUROC) curve and calibration plot, respectively. Cox proportional hazards regression was used to assess whether the NELA-predicted risks were an independent predictor of hospital mortality. Of the 502 patients included, 168 (33.5%) patients had a NELA-predicted risk >10%, and of these, 93 (55.4%) were admitted to a critical care unit in a planned fashion immediately after surgery. The NELA model had a good ability to discriminate between survivors and non-survivors (AUROC 0.892, 95% confidence intervals 0.854 to 0.93, P <0.001). However, the model was not perfectly calibrated, with the predicted risks tending to overestimate the observed risks of mortality, especially when the predicted risks were >50%. A high NELA-predicted risk remained significantly associated with mortality after adjusting for other covariates, including sepsis and plasma lactate concentration, suggesting that it is a reliable screening tool for identifying high-risk patients requiring emergency laparotomy.

Long-term outcomes after using retrievable vena cava filters in major trauma patients with contraindications to prophylactic anticoagulation.

PURPOSE: To investigate the long-term outcomes of using vena cava filters to prevent symptomatic pulmonary embolism (PE) in major trauma patients who have contraindications to prophylactic anticoagulation. METHODS: This was an a priori sub-study of a randomized controlled trial (RCT) involving long-term outcome data of 223 patients who were enrolled in Western Australia. State-wide clinical information system, radiology database and death registry were used to assess long-term outcomes, including incidences of venous thromboembolism, venous injury and mortality beyond day-90 follow-up. RESULTS: The median follow-up time of 198 patients (89%) who survived beyond 90 days was 65 months (interquartile range 59-73). Ten patients (5.1%) died after day-90 follow-up; and four patients developed venous thromboembolism, including two with symptomatic PE, all allocated to the control group (0 vs 4%, p = 0.043). Inferior vena cava injuries were not recorded in any patients. The mean total hospitalization cost, including the costs of the filter and its insertion and removal, to prevent one short- or long-term symptomatic PE was A$284,820 (€193,678) when all enrolled patients were considered. The number of patients needed to treat (NNT = 5) and total hospitalization cost to prevent one symptomatic PE (A$1,205 or €820) were, however, substantially lower when the filter was used only for patients who could not be anticoagulated within seven days of injury. CONCLUSION: Long-term complications related to retrievable filters were rare, and the cost of using filters to prevent symptomatic PE was acceptable when restricted to those who could not be anticoagulated within seven days of severe injury.

COVID-19 Serosurvey of Frontline Healthcare Workers in Western Australia.

We aimed to study COVID-19 infection in healthcare workers (HCWs) during the first wave in a setting of low community incidence prior to HCW vaccination. We performed a cross-sectional study of frontline HCWs in two tertiary hospitals in Western Australia with questionnaire and testing for SARS-CoV-2 IgG antibodies, using a screening assay followed by confirmatory assays for initial reactive results. 799 Frontline HCWs were enrolled in the study, working in the emergency department (n = 194, 24.2%), ICU (n = 176, 22.0%), respiratory ward (n = 20, 2.5%), COVID clinic (n = 37, 4.6%), and theatre (n = 222, 28%). 189 (23.6%) were doctors, 327 (41.0%) nurses, and 283 (35.4%) other. Contact with a known COVID-19-positive patient occurred at work for 337 (42.1%), and outside work for 10 (1.2%). Four were diagnosed with COVID-19 by PCR, acquired overseas in two cases and related to healthcare work in two cases (one acquired from a colleague and one possibly acquired from patient contact in the healthcare setting). Nine HCWs had reactive screening serology, and three had confirmed positive IgG (these three were PCR-positive cases). Infection control procedures in the setting of low community incidence were effective at preventing HCW acquisition of COVID-19 infection.

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

A prospective ex vivo biomechanical analysis of retrievable inferior vena cava filters.

OBJECTIVE: In the present study, we investigated the structural integrity of inferior vena cava (IVC) filters after their retrieval. METHODS: A prospective ex vivo biomechanical analysis was performed of the structural integrity of 100 IVC filters used in a randomized controlled trial to evaluate the effectiveness of prophylactic IVC filters in preventing mortality or symptomatic pulmonary embolism in major trauma patients. RESULTS: Of the 100 included patients, 7 (7%) had required more than one attempt to remove the filter. The median duration of the filter left in situ was 54 days (interquartile range, 17-101 days). During the initial attempt to remove six filters (6%), thrombi were found entrapped and required 4 weeks of systemic anticoagulation therapy before the filters could be removed in a second attempt. A positive correlation was found between the duration of the filter left in situ and the loss in metallic elasticity of the nitinol alloy of the filter struts (Pearson correlation coefficient, 0.232; P = .008). One filter was adherent to the IVC wall and required open surgical removal 227 days after its initial placement. One of the six long struts of the filter had been fractured during the removal process, with evidence of hardening to bending stress in the remaining five struts of the fractured filter compared with the struts of the 25 intact filters. Fibrous endothelial tissue (73%) and thrombi (33%) adherent to the retrieved filters were frequently observed. The presence of adherent fibrous tissue was not significantly related statistically to the duration of the filter left in situ (P = .353) but was more common among the patients who had had a delay in receiving prophylactic anticoagulation therapy (mean difference, 2 days; 95% confidence interval, 0.6-3.3; P = .039). CONCLUSIONS: Metallic fatigue might account for IVC filter strut fractures. Fibrous endothelial tissue adherent to the filters was common, especially for those with a delay in receiving prophylactic anticoagulation therapy.

Endothelial biomarkers of thrombosis in critically ill patients with acquired coagulopathy: a prospective cohort study.

Background: It remains largely unknown whether endothelial biomarkers can be used to predict thromboembolism in critically ill patients with an acquired coagulopathy. Materials & methods: The ability of syndecan-1, P-selectin and microRNA expressions to predict thromboembolism were assessed in 40 critically ill coagulopathic patients. Results: The area under the receiver operating characteristic curves for syndecan-1, P-selectin and the four differentially expressed microRNAs - determined by real-time qPCR analysis - to predict thromboembolism (n = 10, 25%) were 0.71 (95% CI: 0.52-0.89), 0.73 (95% CI: 0.52-0.95) and >0.80, respectively. Syndecan-1 and P-selectin concentrations were also significantly correlated with one another (R = 0.41, p = 0.008). Conclusion: Endothelial function biomarkers, including endothelial microRNA expressions, were associated with subsequent thromboembolism in critically ill patients who had a deranged coagulation profile.

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs.

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.