Normobaric Oxygen Therapy in Acute Stroke: A Systematic Review and Meta-Analysis.

PURPOSE: Normobaric oxygen (NBO) is potentially a readily accessible neuroprotective therapy. We undertook a systematic review to assess NBO in acute stroke. METHODS: MEDLINE, EMBASE, and CENTRAL databases were searched to December 2020. Randomized controlled trials of NBO administered <7 days after stroke to normoxic patients with no other indication for oxygen were identified. Data on early neurological recovery; functional outcome; mortality; oxygen saturation, and imaging markers were collected. FINDINGS: Fifteen publications involving 12 cohorts and 9,255 participants were identified. One study with 8,003 participants had low risk of bias, but the designs of smaller trials had limitations. Ninety-seven per cent of participants were in studies of low-flow oxygen (≤4 L/min). 82.8% had ischaemic stroke. Median time to treatment was 19.3 h. Meta-analysis demonstrated no significant effect on: reduction in National Institutes of Health Stroke Scale at 7 days in all stroke or ischaemic stroke only (mean difference -0.16 [-1.11 to 0.80] and -0.73 [-3.54 to 2.08], respectively); modified Rankin scale at 3-6 months of follow-up (combined standardized mean difference [SMD] -0.08 [-0.38 to 0.22]; 3 months SMD -0.01 [-0.03 to 0.029]; 6-month SMD -0.20 [-1.49 to 1.09]), or mortality (odds ratio 1.15 [0.87-1.53]). DISCUSSION: The majority of patients were administered low-flow oxygen in the sub-acute phase. Intervention strategies targeted at modification of early tissue survival (higher oxygen delivery and administration at early time points when significant volumes of viable tissue persist) have not been tested adequately. CONCLUSION: Studies of NBO have shown no significant effect on early neurological recovery, functional outcome, or mortality in acute stroke. Oxygen has been predominantly low-flow and commenced in the sub-acute phase.

Real-world uptake, safety profile and outcomes of docetaxel in newly diagnosed metastatic prostate cancer.

OBJECTIVES: To investigate the uptake, safety and efficacy of docetaxel chemotherapy in hormone-naïve metastatic prostate cancer (mPC) in the first year of use outside of a clinical trial. PATIENTS AND METHODS: Patients in the West of Scotland Cancer Network with newly diagnosed mPC were identified from the regional multidisciplinary team meetings and their treatment details were collected from electronic patient records. The rate of febrile neutropenia, hospitalisations, time to progression, and overall survival were compared between those patients who received docetaxel and androgen-deprivation therapy (ADT), or ADT alone using survival analysis. RESULTS: Of the 270 eligible patients, 103 received docetaxel (38.1%). 35 patients (34%) were hospitalised and there were 17 episodes of febrile neutropenia (16.5%). Two patients (1.9%) died within 30 days of chemotherapy. Patients who received ADT alone had an increased risk of progression (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.27-3.25; log-rank test, P = 0.002) and had an increased risk of death (HR 5.88, 95% CI: 2.52-13.72; log-rank test, P = 0.001) compared to the docetaxel group. The risk of febrile neutropenia was nine-times greater if chemotherapy was started within 3 weeks of ADT initiation (95% CI: 1.22-77.72; P = 0.032). CONCLUSION: Docetaxel chemotherapy in hormone-naïve mPC has significant toxicities, but has a similar effect on time to progression and overall survival as seen in randomised trials. Chemotherapy should be started at ≥3 weeks after ADT.

Effect of prior statin use on outcome after severe traumatic brain injury in a South-East Asian population.

INTRODUCTION: Traumatic brain injury (TBI) is a global concern associated with high mortality and morbidity. Costs to individuals and society are extensive due to poor recovery, long-term disability and the young age group affected. Statins have emerged as potential therapeutic agents in TBI. This study aimed to investigate the protective effect of statins in severe TBI. METHODS: This case-control study included adults with severe TBI. A sliding dichotomy approach was used to dichotomize mortality at 14-days and Glasgow Outcome Score (GOS) at 6 months. Logistic regression analysis was used to calculate the odds ratios (OR) for 14-day mortality and 6-month GOS. RESULTS: Equivalent cohorts of 59 age- and sex-matched statin and non-statin users were selected, resulting in population of 118 (mean age = 70.2 years, SD = 10.3), with a median Glasgow Coma Score of 5. Statins did not reduce the likelihood of mortality at 14 days (adjusted OR = 1.23, p = 0.68) or unfavourable outcome at 6 months (adjusted OR = 1.19, p = 0.78). CONCLUSIONS: Despite increasing evidence for benefit of statins in TBI, this study in an Asian population does not support this association, demonstrating no significant improvement in outcome for statin users. Further research is required to understand the mechanisms and impact of statins in TBI.

Size and Location of Ruptured Intracranial Aneurysms: A 5-Year Clinical Survey.

BACKGROUND: Prospective international cohort trials have suggested that incidental cerebral aneurysms with diameters less than 10 mm are unlikely to rupture. Consequently, small ruptured cerebral aneurysms should rarely be seen in clinical practice. To verify this theory, dimensions and locations of ruptured cerebral aneurysms were analyzed across the state of Tasmania, Australia. METHODS: We retrospectively reviewed medical records and diagnostic tests of all patients admitted with ruptured cerebral aneurysms during a 5-year interval. Aneurysm location, maximum size, dome-to-neck ratio, volume, and presence of daughter sacs were determined by preoperative digital subtraction angiography or computed tomography angiography. RESULTS: A total of 131 ruptured cerebral aneurysms were encountered and treated by microsurgical clipping (n = 59) or endovascular techniques (n = 72). The mean maximum aneurysm diameter was 6.4 ± 3.7 mm, dome-to-neck ratio 2 ± 0.8, aneurysm volume 156 ± 372 mm(3), and daughter sacs were present in 70 aneurysms (53.4%). The anterior communicating artery was the most common location (37.4%). Cumulative maximum diameters of ruptured aneurysms were ≤5 mm in 49%, ≤7 mm in 73%, and ≤10 mm in 90%. CONCLUSIONS: Despite findings from prospective international cohort trials, small ruptured intracranial aneurysms are common in clinical practice. In consequence, it seems important to identify those patients with small but vulnerable unruptured aneurysms before conservative management is considered.

External validation of the CRASH and IMPACT prognostic models in severe traumatic brain injury.

An accurate prognostic model is extremely important in severe traumatic brain injury (TBI) for both patient management and research. Clinical prediction models must be validated both internally and externally before they are considered widely applicable. Our aim is to independently externally validate two prediction models, one developed by the Corticosteroid Randomization After Significant Head injury (CRASH) trial investigators, and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) group. We used a cohort of 300 patients with severe TBI (Glasgow Coma Score [GCS] ≤8) consecutively admitted to the National Neuroscience Institute (NNI), Singapore, between February 2006 and December 2009. The CRASH models (base and CT) predict 14 day mortality and 6 month unfavorable outcome. The IMPACT models (core, extended, and laboratory) estimate 6 month mortality and unfavorable outcome. Validation was based on measures of discrimination and calibration. Discrimination was assessed using the area under the receiving operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. In the NNI database, the overall observed 14 day mortality was 47.7%, and the observed 6 month unfavorable outcome was 71.0%. The CRASH base model and all three IMPACT models gave an underestimate of the observed values in our cohort when used to predict outcome. Using the CRASH CT model, the predicted 14 day mortality of 46.6% approximated the observed outcome, whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to 0.89, and good overall calibration. We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI.

Modulated Raman spectroscopy for enhanced identification of bladder tumor cells in urine samples.

Standard Raman spectroscopy (SRS) is a noninvasive technique that is used in the biomedical field to discriminate between normal and cancer cells. However, the presence of a strong fluorescence background detracts from the use of SRS in real-time clinical applications. Recently, we have reported a novel modulated Raman spectroscopy (MRS) technique to extract the Raman spectra from the background. In this paper, we present the first application of MRS to the identification of human urothelial cells (SV-HUC-1) and bladder cancer cells (MGH) in urine samples. These results are compared to those obtained by SRS. Classification using the principal component analysis clearly shows that MRS allows discrimination between Raman spectra of SV-HUC-1 and MGH cells with high sensitivity (98%) and specificity (95%). MRS is also used to distinguish between SV-HUC-1 and MGH cells after exposure to urine for up to 6 h. We observe a marked change in the MRS of SV-HUC-1 and MGH cells with time in urine, indicating that the conditions of sample collection will be important for the application of this methodology to clinical urine samples.