Plasma creatine kinase indicates major amputation or limb preservation in acute lower limb ischemia

ObjectiveAcutely ischemic limbs are often of uncertain viability. To assist operative management, this study determined prospectively which indicators on admission were the best predictors of major amputation and, conversely, limb preservation.MethodsData were collected on admission. Presenting complaint, history, clinical assessment, and blood test results, including creatine kinase (CK), were recorded. Surgical procedures were noted—in particular, the presence or absence of major amputation by death or discharge. The setting was a tertiary vascular referral center in a university teaching hospital. Subjects included all patients referred as emergency cases to the vascular unit over an 18-month period who were admitted for inpatient management with acute lower limb ischemia. The main outcome measure was major amputation.ResultsA total of 97 patients with acute ischemia were studied prospectively (51 men and 46 women). Twenty-one patients (21.6%) underwent major amputation. Previous vascular surgery (P = .012), mottling (P = .001), sensory loss (P = .003), motor loss (P = .001), muscle tenderness (P < .001), absent ankle Doppler signals (P = .008), neutrophilia (P = .011), and increased CK (P < .001) were significantly associated with major amputation. If CK was normal, the risk of major amputation was 4.6% (95% confidence interval, 0.0%-9.7%). If CK was increased, the risk was 56.2% (95% CI, 39.1%-73.4%).ConclusionsSpecific clinical findings were significantly associated with major amputation. Of these, only CK had a positive predictive value greater than 50%. Plasma CK can assist operative management of acute lower limb ischemia by quantifying prospectively the risk of major amputation or limb preservation on admission

Substantial metabolic activity of human brown adipose tissue during warm conditions and cold-induced lipolysis of local triglycerides

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

ERCP: A single-centre study of 1020 cases

Introduction : En raison de l’essor de la cholangio-pancréatographie IRM (CPIRM) et de l’échoendoscopie, dans l’exploration des pathologies biliaires et pancréatiques, la cholangiopancréatographie rétrograde (ERCP) souvent source de complications, est actuellement, nettement moins prisée en tant que méthode diagnostique. Cette étude a pour but d’évaluer l’ERCP sur une série consécutive de patients de façon à cerner les types et taux de complications liées à cette procédure et à déterminer si les réticences formulées quant à son utilisation, sont justifiées. Méthodes : L’étude portait sur une série consécutive de patients soumis à ERCP, examen réalisé par un seul opérateur sur une période de 8 ans dans un petit hôpital général de district du sud-ouest de l’Ecosse. Les indications de la CPRE ont été enregistrées de même que les taux d’amylases sériques dans les 24 heures après l’examen. Les complications précoces liées à la CPRE étaient documentées et les dossiers des patients réadmis à l’hôpital dans les 30 jours suivant la procédure, ont été revus de façon à mettre en évidence toute complication tardive liée à l’examen. Résultats : Durant la période de l’étude, 1020 patients ont été évalués. La plupart (64,7 %) ont été soumis à des CPRE thérapeutiques qui pour la majorité, étaient pratiquées pour suspicion de lithiase de la voie biliaire principale (56 %). Le taux de complication global a été de 2,6%mais il n’y a pas de différence significative entre le groupe diagnostique et le groupe thérapeutique. Une pancréatite est survenue au cours de 15 ERCP (1,6 %) mais c’est cependant une complication rare qui a touché seulement 2 patients chez lesquels un cathétérisme sélectif de la voie biliaire principale avait été effectué. Dans tous les cas, il s’agissait d’une pancréatite modérée résolue par traitement conservateur uniquement. L’hémorragie a compliqué 6 ERCP (0,6 %). Nous n’avons enregistré aucune perforation liée à l’ERCP, ni complications cardio-pulmonaires, ni mortalité. Cinq patients (0,5%) ont développé une cholangite nécessitant une réadmission à l’hôpital dans les 30 jours suivant l’ERCP. Conclusions : Malgré la contre-publicité faite à l’ERCP au regard de ses complications, les résultats de cette étude ont montré que cette procédure était sûre entre des mains expérimentées avec un taux extrêmement bas de complications précoces ou tardives. Dans cette série, le taux de pancréatite était faible mais pourrait être encore réduit par cathétérisme sélectif de la voie biliaire principale

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications