A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden

Incidence of Nonunion of the Hallux Interphalangeal Joint Arthrodesis: A Systematic Review.

Hallux interphalangeal joint arthrodesis is an effective procedure to treat pain and provide stability and is often performed for intrinsic pain to the hallux interphalangeal joint. Additionally, this procedure is typically used in concert with the Jones tenosuspension. Although this as an accepted technique, the available data are scant, and questions remain regarding nonunion rates and contributory factors to poor healing. A systematic review of the reported data were undertaken to determine the rate of nonunion for hallux interphalangeal joint arthrodesis. Seven studies involving 313 hallux interphalangeal joint arthrodeses met the inclusion criteria. The nonunion rate was 28.3% at a weighted mean follow-up period of 8.4 months. The overall complication rate was 33.0%. Considering the increased rate of complications and nonunion rate for this commonly used procedure, additional prospective comparative analyses are needed regarding this topic to identify important patient demographic data and determine superior fixation constructs

Rate of Development of Hallucal Interphalangeal Degenerative Joint Disease After First Metatarsophalangeal Joint Arthrodesis: A Retrospective Radiographic Analysis.

The development of hallux interphalangeal joint (IPJ) arthritis after an arthrodesis of the first metatarsophalangeal joint has been established in the literature. However, the significance has not been well reported. A retrospective, radiographic review of patients who had undergone a first metatarsophalangeal joint arthrodesis was performed. The Coughlin classification for degree of arthritic degeneration, hallux abductus angle, and hallux interphalangeus angle were measured in 107 radiographs of 103 patients preoperatively and postoperatively. Postoperative angles were measured immediately following surgery at approximately 6 weeks, 3 months, 6 months, 12 months, and 24 months. We found that the hallux abductus angle had decreased in the patients postoperatively; however, the hallux abductus interphalangeus angle increased on average after first metatarsophalangeal fusion. The majority of patients started with a Coughlin classification I of the hallux IPJ, which remained unchanged over the postoperative period, with no statistically significant difference in IPJ degeneration in the patients with or without fusion of the first metatarsophalangeal joint. In addition, no patients had a symptomatic hallux IPJ postoperatively within our limited study period. Further prospective studies would be beneficial with longer follow-up times to assess IPJ degeneration following first metatarsophalangeal joint fusions

Effectiveness of the Cadaver Lab in Podiatric Surgery Residency Programs.

Since the inception of the first surgical training system by Sir William Stewart Halsted, resident surgical skill development has been promulgated in teaching hospitals. Currently, the Council on Podiatric Medical Education does not mandate the availability of a cadaver lab as a residency curriculum requirement. The purpose of the present study is to assess the structure of the cadaver lab and availability in the current podiatric surgical training programs. A survey was sent electronically to 229 American Association of Colleges of Podiatric Medicine-approved residency programs, excluding OhioHealth, across all residency programs. A total of 173 (6.9%) residents from 74 (32.3%) residency programs completed the survey. This survey analyzed the characteristics and perception of the current state of cadaver lab in podiatric residency. The most reported type of cadaver labs available were medical company sponsored and hospital sponsored. Other hands-on training, including inanimate simulators (n = 24) and animal models (n = 5), was also reported. Overall, 87.9% of the surveyed residents found that cadaver lab is either extremely beneficial (57.8%) or somewhat beneficial (30.1%). The most important factors perceived in a successful cadaver lab were faculty instruction (n = 78), accessibility of lab (n = 46), and availability of instrumentation/hardware (n = 26). This qualitative survey is the first study to address the uniformity, perception, and potential value of the cadaver lab in a podiatric surgical residency

Outcomes of Ankle Arthrodesis Conversion to Total Ankle Arthroplasty: A Systematic Review.

Ankle arthrodesis (AA) provides reliable pain relief, good patient satisfaction scores, and improved overall function. However, this procedure has been associated with numerous complications and sequelae, such as pseudoarthrosis, malunion, gait abnormalities, increased demand on surrounding joints, and a long period of convalescence. Conversion to total ankle arthroplasty (TAA) is a potential option in the management of these complex and challenging situations. The purpose of this study is to investigate the outcomes of AA conversion to TAA. A systematic review of electronic databases was performed. Six studies involving 172 ankles met inclusion criteria. The weighted mean preoperative Visual Analogue Scale (VAS) score at the time of TAA conversion was 7.8 and the weighted mean postoperative VAS score at the time of final follow-up was 2.5. The weighted mean preoperative AOFAS score at the time of TAA conversion was 32 and the weighted mean postoperative AOFAS score at the time of final follow-up was 72.4. The rate of salvage tibiotalocalcaneal arthrodesis was 2.3% and rate of transtibial amputation was also 2.3% after attempted conversion from initial AA to TAA. Conversion of AA to TAA appears to be a viable option to improve patient outcomes and prevent extensive hindfoot arthrodesis and transtibial amputation. More prospective studies with consistent reporting of outcomes, complications, and revision rates with long-term follow-up are needed

Standardized local assortativity in networks and systemic risk in financial markets.

The study of assortativity allows us to understand the heterogeneity of networks and the implication of network resilience. While a global measure has been predominantly used to characterize this network feature, there has been little research to suggest a local coefficient to account for the presence of local (dis)assortative patterns in diversely mixed networks. We build on existing literature and extend the concept of assortativity with the proposal of a standardized scale-independent local coefficient to observe the assortative characteristics of each entity in networks that would otherwise be smoothed out with a global measure. This coefficient provides a lens through which the granular level of details can be observed, as well as capturing possible pattern (dis)formation in dynamic networks. We demonstrate how the standardized local assortative coefficient discovers the presence of (dis)assortative hubs in static networks on a granular level, and how it tracks systemic risk in dynamic financial networks

The Incidence of Nonunion of the Naviculocuneiform Joint Arthrodesis:A Systematic Review.

Naviculocuneiform (NC) joint arthrodesis is an effective procedure to treat pain and provide stability to the medial column. Various forms of fixation have been described for NC arthrodesis. Despite this, the available literature is scant and questions remain regarding nonunion rate and contributory factors. A systematic review of the literature was undertaken to determine the rate of nonunion for NC joint arthrodesis. Seven studies involving 139 NC joint arthrodeses met inclusion criteria. The nonunion rate was 6.5% at a weighted mean follow-up of 73.2 months. There is insufficient evidence to provide a practice guideline based on the current literature. Adequately powered prospective clinical trials comparing well-matched patient groups with long-term follow-up are required to limit systematic error and enhance external validity. Specific outcomes measures should include union, functional assessment, complications, and cost-benefit analysis