Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.
Campbell, B. C. V. et al. (2018) Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurology, 17(1), pp. 47-53. (doi:10.1016/S1474-4422(17)30407-6) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/149670/ variables. An alternative approach using propensity-score stratification was also used. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Bias was assessed using the Cochrane tool.Findings: Of 1764 patients in 7 trials, 871 were allocated to endovascular thrombectomy. After exclusion of 74 patients (72 who did not undergo the procedure and 2 with missing data on anaesthetic strategy), 236/797 (30%) of endovascular patients were treated under GA. At baseline, GA patients were younger and had shorter time to randomisation but similar pre-treatment clinical severity compared to non-GA. Endovascular thrombectomy improved functional outcome at 3 months versus standard care in both GA (adjusted common odds ratio (cOR) 1·52, 95%CI 1·09-2·11, p=0·014) and non-GA (adjusted cOR 2·33, 95%CI 1·75-3·10, p<0·001) patients. However, outcomes were significantly better for those treated under non-GA versus GA (covariate-adjusted cOR 1·53, 95%CI 1·14-2·04, p=0·004; propensitystratified cOR 1·44 95%CI 1·08-1·92, p=0·012). The risk of bias and variability among studies was assessed to be low.Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. Funding:The HERMES collaboration was funded by an unrestricted grant from Medtronic to the University of Calgary. Research in contextEvidence before this study between abolition of the thrombectomy treatment effect in MR CLEAN and no effect in THRACE. Three single-centre randomised trials of general anaesthesia versus conscious sedation found either no difference in functional outcome between groups or a slight benefit of general anaesthesia. Added value of this studyThese data from contemporary, high quality randomised trials form the largest study to date of the association between general anesthesia and the benefit of endovascular thrombectomy versus standard care. We used two different approaches to adjust for baseline imbalances (multivariable logistic regression and propensity-score stratification). We found that GA for endovascular thrombectomy, as practiced in contemporary clinical care across a wide range of expert centres during the rand...
, over 7 million confirmed cases and over 400,000 deaths had been recorded across 213 countries and territories [3]. In outbreaks, epidemics, and pandemics, epidemiologists aim to quantify the spread of a disease within a population across space and time. In addition, epidemiologists aim to quantify the rate of disease transmission. This information is then used to inform prevention and mitigation strategies. Although aggressive prevention strategies may be disruptive and costly, such measures may ultimately reduce the burden of morbidity and mortality within a population, as has been demonstrated in previous pandemics, such as the 1918-1920 influenza and the 2009 influenza A (H1N1) pandemics [4, 5]. The first tier of response is containment to prevent the spread of disease before it has a chance to take hold in the community [6]. This may include contact tracing, surveillance in the community through widespread testing, and quarantine measures. However, once a disease has spread through the community, the second tier, mitigation strategies, are necessary to reduce transmission. Interventions include social distancing measures; closure of schools, workplaces, and community facilities; travel restrictions; and individual-level hygiene measures, such as wearing a mask and washing hands [6]. Without mitigation efforts in place, healthcare systems risk being stretched beyond capacity in, for example, intensive care unit (ICU) beds, personal protective equipment (PPE), and ventilators for treating patients with COVID-19. This is why countries who were in the mitigation phase of the pandemic conducted communication campaigns imploring individuals to engage in behaviors to "flatten the curve." Beyond the mitigation tier, state-level actors may put lockdowns in place to further curb transmission. Scope of the problem Asia Countries across Asia were some of the first to experience the outbreak of COVID-19. Many had already had previous experiences dealing with epidemics, including severe acute respiratory syndrome (SARS) from 2002 to 2003, H1N1 flu in 2009, and Middle East Respiratory Syndrome (MERS) in 2014, 2015 and 2018 [7]. Such experiences had prepared governments to respond and made their populations more receptive to restrictive public health measures. Some entities, including South Korea, Mongolia, Hong Kong, and Singapore, initially succeeded in containing the virus through aggressive preemptive measures: transparency in communication, ubiquitous testing, strict quarantine, and thorough disinfectant protocols [7, 8]. South Korea used such measures without ever putting a lockdown in place. After failures in communication during the MERS epidemic in 2015, new standard operating procedures were put in place. By the time COVID-19 arrived, Koreans were willing to
Objective: To characterize the role of steroid hormone and antihormone exposure on neurotrimin (NTM) expression in human leiomyoma and myometrial tissue and cells. Design: Laboratory study of placebo and ulipristal acetate (UPA)-treated patient tissue. In vitro assessment of immortalized myometrial and leiomyoma cell lines after hormone and antihormone exposure. Setting: Academic research center. Patient(s): Not applicable. Interventions(s): Exposure of leiomyoma cell lines to 17b-E 2 , medroxyprogesterone acetate (MPA), UPA, and fulvestrant. Main Outcome Measure(s): Messenger RNA expression quantified with the use of RNASeq analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels quantified by means of Western blot analysis. Immunohistochemistry (IHC) on placebo-and UPA-treated patient uterine tissue specimens. Result(s): Expression of NTM in human uterine leiomyoma specimens according to RNASeq was increased compared with myometrium (5.22 AE 0.57-fold), which was confirmed with the use of qRT-PCR (1.95 AE 0.05). Furthermore, NTM protein was elevated in leiomyoma tissue compared with matched myometrium (2.799 AE 0.575). IHC revealed increased staining intensity in leiomyoma surgical specimens compared with matched myometrium of placebo patients. Western blot analysis in immortalized leiomyoma cell lines demonstrated an up-regulation of NTM protein expression (2.4 AE 0.04). Treatment of leiomyoma cell lines with 17b-E 2 yielded a 1.98 AE 0.11-fold increase in NTM protein expression; however, treatment with fulvestrant showed no significant change compared with control. Leiomyoma cell lines demonstrated a 1.91 AE 0.97-fold increase in NTM protein expression after progesterone treatment. RNASeq analysis demonstrated a reduced expression in patient leiomyoma after UPA treatment (0.75 AE 0.14). Treatment of leiomyoma cells with UPA demonstrated a reduced total NTM protein amount (0.54 AE 0.31) in patients, which was confirmed with the use of IHC (UPA10 147.2 AE 9.40, UPA20 182.8 AE 8.98). In vitro studies with UPA treatment revealed a concentration-dependent effect that supported these findings. Conclusion(s): NTM, a neural cell adhesion molecule, is increased in leiomyoma compared with myometrium in patient tissue and in vitro models after estrogen and progesterone treatment. Down-regulation of expression occurs after UPA treatment, but not after fulvestrant exposure.
Purpose of reviewTurner syndrome is the most common sex chromosome abnormality in female individuals, affecting 1/2000–1/2500 female newborns. Despite the high incidence of this condition, the mechanisms underlying the development of multiorgan dysfunction have not been elucidated.Recent findingsClinical features involve multiple organ systems and include short stature, dysmorphic facial features, delayed puberty and gonadal failure, cardiac and renal abnormalities, audiologic abnormalities, and a high prevalence of endocrine and autoimmune disorders. Paucity of available genotype/phenotype correlation limits the ability of clinicians to provide accurate guidance and management. Given the advent of robust genetic testing and analysis platforms, developments in the genetic basis of disease are materializing at a rapid pace.SummaryThe objective of this review is to highlight the recent advances in knowledge and to provide a framework with which to apply new data to the foundational understanding of the condition.
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