Strengthening Muscle Health of Community-Dwelling Older Adults in Singapore: Evidence Towards Clinical Implementation.

The prevalence of sarcopenia will inevitably increase as the population ages in Singapore, rendering it a growing public health concern with a significant impact on healthcare resources. This article firstly summarizes the current understanding of the epidemiology, diagnosis and management of sarcopenia, focusing on community-dwelling older individuals. Early identification is key to preventing and minimizing muscle loss. Appropriate interventions, including resistance exercise training, nutritional interventions and prehabilitation program, should be tailored to each patient. We suggest several key actions to ultimately improve awareness and overcome challenges in identifying and managing sarcopenia to improve patient outcomes. A paradigm shift where muscle health is seen as an integral component to maintaining good health with longer lifespan is needed. Education - of healthcare professionals and the public - serves as the foundation to improving awareness of muscle health and sarcopenia, and to promoting physical exercise across the age spectrum for sarcopenia prevention. The use of cost-effective evidence-based modalities (e.g., calf circumference measurement, 5-times chair stand test or bioelectric impedance assessment) enable early identification of muscle loss in routine practice. Providing subsidies for nutritional interventions (e.g., oral nutritional supplements) and exercise (e.g., ActiveSG gym membership) would encourage uptake of and adherence to interventions. Further high-quality research on interventions and their outcomes is important to determine the optimal strategy in different patient populations and to demonstrate clinical significance and value of addressing sarcopenia. Having local champions within healthcare institution would facilitate the much-needed change in healthcare culture where muscle health is a part of routine clinical practice.

Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

Serum interleukin-4 is elevated in clinical drug-induced liver injury.

BACKGROUND: Drug-induced liver injury (DILI) remains a challenging diagnosis due to an absence of specific biomarkers. DILI due to volatile anaesthetics (VA-DILI) is characterised by trifluoroacetyl and CYP2E1 antibodies, but may not be seen for weeks after injury. Interleukin-4 (IL-4) may be involved in the production of these antibodies and may serve as a clinically useful early biomarker of VA-DILI. AIM: To prospectively compare serum IL-4 levels between patients who develop VA-DILI and controls following exposure to the volatile anaesthetic. METHODS: A nested case-control study of patients exposed to VA during surgery was conducted. Thirteen DILI cases were identified from the original cohort, and 26 controls were matched according to age, sex and VA agent. Serum samples were collected before and 48-96 h after VA exposure, and analysed for IL-4 using quantitative enzyme-linked immunosorbent assay techniques. RESULTS: There was a statistically significant difference in serum IL-4 in post-VA samples between DILI cases and controls (control: 0.030 pg/mL, IQR: 0.030 - 0.030 pg/mL vs DILI: 0.044 pg/mL, IQR: 0.030 - 0.061 pg/mL; p = 0.039). A greater proportion of DILI cases had post-VA IL-4 levels above the assay lower limit of detection compared to controls (control: 23% vs DILI: 69%; p = 0.013). CONCLUSION: IL-4 is a potential biomarker of DILI. Clinical diagnosis and understanding of DILI disease mechanisms may be improved by further investigation of novel biomarkers, and this IL-4 signal in serum is important as proof of concept for prospective study designs.

Predictors of glaucoma in patients with uveitis and scleritis.

BACKGROUND: To examine risk factors for development of glaucoma in a large cohort of subjects with uveitis and scleritis. METHODS: Retrospective review of subjects diagnosed with uveitis or scleritis between 2006 and 2019 at Auckland District Health Board. Subjects were excluded if they had glaucoma due to another cause. Main outcome measure was development of glaucoma. Data for local steroid use was not available. RESULTS: 3462 eyes of 2414 subjects were included in the study. Mean follow-up was 5.7 years (total follow-up time 19,897 eye years). Median age was 44.3 years and 1189 (49.3%) were female. Glaucoma developed in 222 eyes (6.3%) during the follow-up. Five-year cumulative risk of glaucoma was 6.2% (CI 5.0-7.5%) for anterior uveitis, 5.4% (CI 3.2-9.0%) for intermediate uveitis, 1.6% (CI 0.4-6.7%) for posterior uveitis, 8.7% (CI 6.5-11.7%) for panuveitis, and 3.2% (CI 1.0-9.5%) for scleritis. Five-year cumulative risk of glaucoma was lowest in HLA-B27 uveitis at 0.9% (CI 0.4-2.1%) and highest in viral uveitis 15.1% (CI 10.1-22.3%), sarcoidosis 9.9% (CI 6.1-15.9%) and tuberculosis 9.7% (CI 5.4-17.0%). On multivariate analysis, risk factors for development of glaucoma were older age at presentation, higher presenting intraocular pressure, chronic inflammation, and cystoid macular oedema. CONCLUSIONS: Glaucoma is a common complication of uveitis and scleritis and was more frequent in older subjects, high presenting IOP, chronic inflammation and those with cystoid macular oedema. Local steroid therapy contributes to this, but is not quantifiable in this study. Targeted screening is required to avoid irreversible progression of glaucomatous optic neuropathy.

Atypical meningioma with nodal metastasis: A case report.

INTRODUCTION: Meningiomas are common and usually benign central nervous system neoplasms. These neoplasms are graded into three groups which differ in biological behaviour. Atypical meningioma is an intermediate grade (Grade 2) tumour that is rarely associated with metastases compared to higher grade (Grade 3) meningiomas. CASE REPORT: A 68-year-old lady with a history of multiple craniotomies and hemifacial resections for meningothelial meningioma currently underwent orbital exenteration, tumour debulking and cervical nodal excision for tumour recurrence. Histopathological examination of the tumour showed atypical meningioma, with cervical nodal metastasis. DISCUSSION: This case report presents a rare finding of lymph node metastasis associated with atypical meningioma. The previous history of surgical resection is a known risk factor for metastasis for low to intermediate grade meningioma. Tumour biology and histology are predictors of metastasis. Haematogenous dissemination is the commonest route of metastasis. No standardised management protocol has been developed and the prognosis remains unknown.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Alendronate use in older patients with reduced renal function: challenges and opportunities in clinical practice.

In this retrospective cohort study, alendronate use among older osteoporosis patients (age>65 years) with reduced renal function (creatinine clearance<35ml/min) was not associated with significant deterioration in renal function from baseline nor increased incidence of osteoporotic fractures or acute kidney injury, compared with patients conservatively managed with only calcium/vitamin D supplementation. INTRODUCTION: Oral bisphosphonates are not recommended in patients with creatinine clearance (CrCl) <35ml/min, although this is not supported by post hoc analyses of pivotal oral bisphosphonate studies. As both osteoporosis and renal insufficiency are more prevalent with advancing age, it is important to determine the safety and efficacy of oral bisphosphonates among these patients. METHODS: Patients with CrCl <35ml/min on alendronate (group A, n=98), with CrCl <35ml/min conservatively managed (group B, n=96), and with CrCl ≥35ml/min on alendronate (group C, n=96) were followed up to 22 months. Primary outcomes were mean change in CrCl from baseline in group A compared with groups B and C, respectively. Secondary outcomes were the incidence of osteoporotic fractures and adverse events between groups. RESULTS: There was no significant change in CrCl from baseline when comparing group A (-1.53±6.83ml/min) with group B (0.59±5.17ml/min) (p=0.075), and group A with group C (-3.71±7.54ml/min) (p=0.163). There was no significant increase in incidences of osteoporotic fractures in group A compared with group B (adjusted relative risk (aRR) 2.02, 95% confidence interval (CI) 0.64-6.37) and group A compared with group C (aRR 1.15, 95% CI 0.46-2.89). There was no significant difference in incidences of acute kidney injury (AKI) in group A compared with group B (aRR 0.48, 95% CI 0.20-1.12). Although statistically non-significant, there was an increase in AKI incidence in group A compared with group C (RR 7.84, 95% CI 0.98-62.66). CONCLUSION: Among patients with CrCl <35ml/min, alendronate therapy was not associated with significant deterioration in renal function from baseline. Although not powered for secondary outcomes, there were no statistically significant differences in osteoporotic fracture or AKI incidence between the groups.

Clinical outcomes of acute stroke thrombolysis in neurologist and non-neurologist centres - A comparative study in Malaysia.

BACKGROUND: Thrombolytic therapy with intravenous alteplase is a well-established treatment for acute ischaemic stroke (AIS). However, in Malaysia, treatment prescription is often limited by the availability of neurologists. The objective was to compare the outcomes of acute stroke thrombolysis therapy prescribed by neurologists in the Seberang Jaya Hospital (SJH) and non-neurologists in the Taiping Hospital (TH). METHODS: In this cross-sectional study, all AIS patients who received thrombolytic therapy in SJH and TH between January 2012 and September 2019 were included. Clinical data was extracted from admission records. The outcomes assessed were the percentage of patients who achieved excellent functional outcome at 3 months (modified Rankin scale of 0 to 1), rates of symptomatic intracranial haemorrhage (SICH), and mortality. RESULTS: A total of 63 AIS patients who received thrombolytic therapy were included, of which 37 patients (58.7%) were treated in SJH. The median NIHSS on admission was 12 in SJH and 11.5 in TH. In all 21.6% of patients from SJH and 30.7% of patients from TH achieved favourable functional outcome at 3 months (p=0.412). There were no significant differences between the two centres in terms of the rates of SICH (10.8% in SJH and 3.8% in TH, p=0.314) and 3-month mortality (24.3% versus 12.5%, p=0.203). CONCLUSION: The 3-month functional outcomes and complication rates of stroke thrombolysis in hospitals with or without neurologists are not significantly different. Thus non-neurologist hospitals may be able to provide thrombolysis service to AIS patients safely and effectively.

Facilitators and barriers to the training and maintenance of young persons' advisory groups (YPAGs).

INTRODUCTION: Increasing demands from public and private healthcare coupled with national initiatives in patient-oriented research has led to an increase in avenues to allow patients to be directly involved in research. In particular, the push towards participation of children and youth has resulted in the formation of pediatric patient advisory groups with broad partnerships and consultation requests across the globe. However, there is a lack of evidence to examine the challenges in formation and training of young persons' advisory groups (YPAGs) and management processes required thereafter. PURPOSE AND OBJECTIVES: This study's purpose is to document YPAG formation and training protocols around the world, highlight common strengths, and evaluate pitfalls and challenges. The results from this study will subsequently inform the development of standardized training protocols for children and youth to be piloted globally. METHODS: In this study, 17 select YPAG team leaders from 7 countries were surveyed to determine current training techniques used within existing groups. 17 youth representatives and 16 team leaders were then interviewed to gather further qualitative data on facilitators and barriers that aid or prevent successful initiation and maintenance of these groups. Qualitative interview data was coded and analyzed using NVivo by two independent reviewers (SYC, VWLT). Any inconsistencies in thematic analysis was confirmed by a third reviewer (JB). RESULTS: The most common training topics include consent and assent (64.71%), clinical trials (64.71%), and patient safety (70.59%). There are significant discrepancies to the amount of training received by each team. Most YPAGs out of the 17 groups receive no formal training (58.82%) while training sessions in the remaining 7 groups vary in both duration and frequency. Collectively, meetings ranged from 15  minutes to 6  hours long, with the majority of team meetings being 2-3  hours long (58.82%). The most common training facilitators are a positive relationship with a local hospital (82.35%) and access to a dedicated team coordinator (64.71%). 70.59% of team leaders identified a lack of access to appropriate educational materials available as a drawback to the impact of their YPAG, making this the greatest common barrier. CONCLUSION: Bringing children and youth to the forefront of paediatric trials and clinical research facilitates appropriate patient representation in subsequent research decision-making. There is an urgency to create and implement standardized protocols for the training of children and youth, especially in preparation for national and international research consultations. This low barrier framework may be of special interest to lower-middle-income countries who wish to encourage community participation in healthcare.

Leptomeningeal Relapse of Embryonal Rhabdomyosarcoma after 15 years.

Aim Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour of childhood. We present the case of a late relapse of RMS to the leptomeninges after 15 years. Methods A 20 year old male presented with a 3 week history of headaches and nausea. He previously had RMS of his right ear diagnosed at age 5 years which was treated with concurrent chemoradiotherapy. An MRI Brain and Spine confirmed extensive leptomeningeal disease and CSF analysis confirmed the presence of recurrent embryonal RMS. Results He completed two cycles of cyclophosphamide and topotecan followed by 45Gy/25Fr of craniospinal radiotherapy. Conclusion Late relapses beyond five years can be seen in up to 9% of patients, however very late recurrences (>10 years) are exceedingly rare. Molecular based methods such as gene expression profiling can aid risk stratification and survivorship clinics may become increasingly useful in following patients with high risk features.

Olfactory cell cultures to investigate health effects of air pollution exposure: Implications for neurodegeneration.

Air pollution is a major, global public health concern. A growing body of evidence shows that exposure to air pollutants may impair the brain. Living in highly polluted areas has been linked to several neurodegenerative diseases, where exposure to complex mixtures of air pollutants in urban environments may have harmful effects on brain function. These harmful effects are thought to originate from elevated inflammation and oxidative stress. The olfactory epithelium is a key entry site of air pollutants into the brain as the particles are deposited in the upper airways and the nasal region. A potential source of patient-derived cells for study of air pollutant effects is the olfactory mucosa, which constitutes a central part of the olfactory epithelium. This review first summarizes the current literature on the available in vitro models of the olfactory epithelium. It then describes how alterations of the olfactory mucosa are linked to neurodegeneration and discusses potential therapeutic applications of these cells for neurodegenerative diseases. Finally, it reviews the research performed on the effects of air pollutant exposure in cells of the olfactory epithelium. Patient-derived olfactory epithelial models hold great promise for not only elucidating the molecular and cellular pathophysiology of neurodegenerative disorders, but for providing key understanding about air pollutant particle entry and effects at this key brain entry site.

Dedifferentiated endometrioid adenocarcinoma of the uterus: A case series and review of literature.

Introduction Dedifferentiated endometrioid adenocarcinoma (DEAC) was first described in 2007. However, it has only been recognised as a distinct subtype of endometrioid adenocarcinoma in the last 1-2 years. DEAC is a more aggressive histological subtype and carries a poorer prognosis. Patients with DEAC tend to present with advanced disease compared the other endometrioid adenocarcinomas. Methodology The study is a retrospective review of patients with DEAC diagnosed in two institutions in Singapore between January 2012 and October 2017. Results 7 patients were diagnosed with DEAC. The mean age was 56.4 years. All patients presented with either abnormal uterine bleeding or post menopausal bleeding. Out of the 7 patients, one was diagnosed with Stage 2 disease, 5 were diagnosed with Stage 3 disease and 1 was diagnosed with Stage 4 disease. One patient had neoadjuvant chemotherapy, followed by surgery, and completion chemotherapy post surgery. The other 6 patients (87.5%) underwent primary debulking surgery. Out of these 6 patients, 5 patients had adjuvant chemotherapy post surgery and one patient had both adjuvant chemotherapy and radiotherapy. Lymphovascular invasion was found in 71.4% of the cases. Conclusion DEAC is a more aggressive histological subtype of endometrioid adenocarcinomas. Better awareness of this condition can lead to proper diagnosis and treatment.

The efficacy of intratympanic steroid injection for the treatment of idiopathic sudden sensorineural hearing loss.

OBJECTIVE: A systemic steroid is known to have a potential to recover hearing after idiopathic sudden sensorineural hearing loss (ISSHL). However, lately many centres have introduced the use of intratympanic (IT) steroid therapy as an option. We reviewed our experience in the treatment of patients with ISSHL looking at the overall success of using systemic steroid, IT steroid injections as salvage therapy and primary IT steroid injection. METHODS: A retrospective study was conducted on 20 patients who had suffered from ISSHL from January 1, 2012, to December 31, 2017. ISSHL is defined as a rapid decline in hearing over three days or less affecting three or more frequencies by 30dB or greater. Comparison between the mode of steroid therapies and improvement in patients was done. At least 15dB improvement in pure tone audiogram (PTA) was considered as successful therapeutic intervention. RESULTS: Twenty male and female patients who fit the inclusion and exclusion criteria were included. The mean age of the patients was 41.4 years with a range from 13 to 72 years. Ninety percent patients presented with unilateral ISSHL involvement. Eight ears of patients who received systemic steroid therapy alone had improved hearings (75%). Out of seven ears from six patients who received salvage therapy, four ears (57.1 %) had improvement in PTA. Seven ears showed improvement in PTA from a total of eight patients who primarily received IT injections. CONCLUSIONS: IT steroid therapy promises a favourable outcome in the improvement of the hearing, as compared to systemic steroid administration. Its usage is recommended not only for salvage therapy but should be used as primary treatment especially in those with co- morbidities.

Cheiroarthropathy and tendinopathy in diabetes.

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non-enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build-up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy.

Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers.

There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.

Development of a 10 kHz high harmonic source up to 140 eV photon energy for ultrafast time-, angle-, and phase-resolved photoelectron emission spectroscopy on solid targets.

We present a newly developed high harmonic beamline for time-, angle-, and carrier-envelope phase-resolved extreme ultraviolet photoemission spectroscopy on solid targets for the investigation of ultrafast band structure dynamics in the low-fs to sub-fs time regime. The source operates at a repetition rate of 10 kHz and is driven by 5 fs few-cycle near-infrared laser pulses generating high harmonic radiation with photon energies up to 120 eV at a feasible flux. The experimental end station consists of a complementary combination of photoelectron detectors which are able to spectroscopically address electron dynamics both in real and in k-space. The versatility of the source is completed by a phase-meter which allows for tracking the carrier-envelope phase for each pulse and which is synchronized to the photoelectron detectors, thus enabling phase sensitive measurements on the one hand and the selection of single attosecond pulses for ultimate time resolution in pump-probe experiments on the other hand. We demonstrate the applicability of the source by an angle- and carrier-envelope phase-resolved photoemission measurement on a tungsten (110) surface with 95 eV extreme ultraviolet radiation.

The Efficacy of a Group Cognitive Behavioral Therapy for War-Affected Young Migrants Living in Australia: A Cluster Randomized Controlled Trial.

Background: Preventative and treatment programs for people at risk of developing psychological problems after exposure to war trauma have mushroomed in the last decade. However, there is still much contention about evidence-based and culturally sensitive interventions for children. The aim of this study was to examine the efficacy of the Teaching Recovery Techniques in improving the emotional and behavioral outcomes of war-affected children resettled in Australia. Methods and Findings: A cluster randomized controlled trial with pre-test, post-test, and 3-month follow-up design was employed. A total of 82 participants (aged 10-17 years) were randomized by school into the 8-week intervention (n = 45) or the waiting list (WL) control condition (n = 37). Study outcomes included symptoms of post-traumatic stress disorder, depression, internalizing and externalizing problems, as well as psychosocial functioning. A medium intervention effect was found for depression symptoms. Participants in the intervention condition experienced a greater symptom reduction than participants in the WL control condition, F(1, 155) = 5.20, p = 0.024, partial η2 = 0.07. This improvement was maintained at the 3-month follow-up, F(2, 122) = 7.24, p = 0.001, partial η2 = 0.20. Conclusions: These findings suggest the potential benefit of the school and group-based intervention on depression symptoms but not on other outcomes, when compared to a waiting list control group. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12611000 948998.

A proposal for a new scoring system to predict difficult ventilation through a supraglottic airway.

BACKGROUND: The aim of this study was to propose and validate a new clinical score to predict difficult ventilation through a supraglottic airway device. METHODS: The score was proposed from our previously reported derivation data, and we prospectively validated the score in 5532 patients from November 2013 to April 2014. Predictive accuracy of the score was compared by the area under the receiver operating characteristic (ROC) curve (AUC). We assigned point values to each of the identified four risk factors: male, age >45 yr, short thyromental distance, and limited neck movement, their sum composing the score. The score ranged between 0 and 7 points. The optimal predictive level of the score was determined using ROC curve analysis. RESULTS: The AUC of the score was 0.75 (95% CI 0.66 to 0.84) in the validation data set, and was similar to that in the derivation data set (0.80; 95% CI 0.75 to 0.86). In derivation and validation data sets, the incidence of low risk categories (scores 0-3) was 0.42% vs 0.32% and of high risk categories (scores 4-7) was 3% vs 1.7% respectively. A score 4 or greater is associated with a six to seven fold increased risk of difficult ventilation through a supraglottic airway device. CONCLUSIONS: The new score for prediction of difficult ventilation through a supraglottic airway device is easy to perform and reliable, and could help anaesthetists plan for difficult airway management.

International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

Mechanical signatures of microbial biofilms in micropillar-embedded growth chambers.

Biofilms are surface-attached communities of microorganisms embedded in an extracellular matrix and are essential for the cycling of organic matter in natural and engineered environments. They are also the leading cause of many infections, for example, those associated with chronic wounds and implanted medical devices. The extracellular matrix is a key biofilm component that determines its architecture and defines its physical properties. Herein, we used growth chambers embedded with micropillars to study the net mechanical forces (differential pressure) exerted during biofilm formation in situ. Pressure from the biofilm is transferred to the micropillars via the extracellular matrix, and reduction of major matrix components decreases the magnitude of micropillar deflections. The spatial arrangement of micropillar deflections caused by pressure differences in the different biofilm strains may potentially be used as mechanical signatures for biofilm characterization. Hence, we submit that micropillar-embedded growth chambers provide insights into the mechanical properties and dynamics of the biofilm and its matrix.