Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.

Pre-clinical In Vitro Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) is a feared complication. Prevention is of the utmost importance and vascular graft coatings (VGCs) could offer a potential to do this, with in vitro research a first crucial step. The aim of this study was to summarise key features of in vitro models investigating coating strategies to prevent VGI in order to provide guidance for the setup of future translational research. DATA SOURCES: A comprehensive search was performed in MEDLINE, Embase, and Web of Science. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). In vitro models using a VGC and inoculation of the graft with a pathogen were included. The type of graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 45 papers met the inclusion criteria. The majority used polyester grafts (68.2%). Thirty-one studies (68.9%) included antibiotics, and nine studies (20%) used a commercial silver graft in their protocol. New antibacterial strategies (e.g., proteolytic enzymes) were investigated. A variety of testing methods was found and focused mainly on bacterial adherence, coating adherence and dilution, biofilm formation, and cytotoxicity. Ninety-three per cent of the studies (n = 41) were considered unreliable. CONCLUSION: Polyester is the preferred type of graft to coat on. The majority of coating studies are based on antibiotics; however, new coating strategies (e.g., antibiofilm coating) are coming. Many in vitro setups are available. In vitro studies have great potential, they can limit the use, but cannot replace in vivo studies completely. This paper can be used as a guidance document for future in vitro research.

The impact of therapeutics on mortality in hospitalised patients with COVID-19: systematic review and meta-analyses informing the European Respiratory Society living guideline.

Hospitalised patients with coronavirus disease 2019 (COVID-19) have a high mortality rate. There are an increasing number of published randomised controlled trials for anti-inflammatory, anti-viral and other treatments. The European Respiratory Society Living Guidelines for the Management of Hospitalised Adults with COVID-19 were published recently, providing recommendations on appropriate pharmacotherapy.Patient, Intervention, Comparator and Outcomes questions for key interventions were identified by an international panel and systematic reviews were conducted to identify randomised controlled trials meeting the inclusion criteria. The importance of end-points were rated, and mortality was identified as the key "critical" outcome for all interventions. Random-effects meta-analysis was used to pool studies and provide effect estimates for the impact of treatments on mortality.Corticosteroids, hydroxychloroquine, azithromycin, remdesivir, anti-interleukin (IL)-6 monoclonal antibodies, colchicine, lopinavir/ritonavir and interferon-ß have been reviewed.Our results found further evidence in support of the use of corticosteroids, particularly dexamethasone, and anti-IL-6 receptor monoclonal antibody therapy. These data support the need to identify additional therapies with beneficial effects on mortality.

Definition of long-bone nonunion: A scoping review of prospective clinical trials to evaluate current practice.

AIM: Although nonunions are among the most common complications after long-bone fracture fixation, the definition of fracture nonunion remains controversial and varies widely. The aim of this study was to identify the definitions and diagnostic criteria used in the scientific literature to describe nonunions after long-bone fractures. METHODS: A comprehensive literature search was performed in PubMed, Cochrane Library, Web of Science, and Embase. Prospective clinical studies, in which adult long-bone fracture nonunions were investigated as main subject, were included in this analysis. Data on nonunion definitions described in each study were extracted and collected in a database. RESULTS: Although 148 studies met the inclusion criteria, only 50% (74/148) provided a definition for their main study subject. Nonunion was defined in these studies based on time-related criteria in 85% (63/74), on radiographic criteria in 62% (46/74), and on clinical criteria in 45% (33/74). A combination of clinical, radiographic and time-related criteria for definition was found in 38% (28/74). The time interval between fracture and the time point when authors defined an unhealed fracture as a nonunion showed considerable heterogeneity, ranging from three to twelve months. CONCLUSION: In the current orthopaedic literature, we found a lack of consensus with regard to the definition of long-bone nonunions. Without valid and reliable definition criteria for nonunion, standardization of diagnostic and treatment algorithms as well as the comparison of clinical studies remains problematic. The lack of a clear definition emphasizes the need for a consensus-based approach to the diagnosis of fracture nonunion centred on clinical, radiographical and time-related criteria.

Pre-clinical in vivo Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) remains an important complication with a high mortality and morbidity rate. Currently, studies focusing on the role of vascular graft coatings in the prevention of VGI are scarce. Therefore, the aims of this study were to survey and summarise key features of pre-clinical in vivo models that have been used to investigate coating strategies to prevent VGI and to set up an ideal model that can be used in future preclinical research. DATA SOURCES: A systematic review was conducted in accordance with the Preferred reporting items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in MEDLINE (PubMed), Embase, and Web of Science. REVIEW METHODS: For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). The type of animal model, graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 94 papers focusing on in vivo testing were included. Staphylococcus aureus was the organism most used (n = 65; 67.7%). Most of the graft types were polyester grafts. Rifampicin was the most frequently used antibiotic coating (n = 43, 48.3%). In the outcome assessment, most studies mentioned colony forming unit count (n = 88; 91.7%) and clinical outcome (n = 72; 75%). According to the ToxRTool, 21 (22.3%, n = 21/94) studies were considered to be not reliable. CONCLUSION: Currently published in vivo models are very miscellaneous. More attention should be paid to the methodology of these pre-clinical reports when transferring novel graft coatings into clinical practice. Variables used in pre-clinical reports (bacterial strain, duration of activity coating) do not correspond well to current clinical studies. Based on the results of this review, a proposal for a complete and comprehensive set up for pre-clinical invivo testing of anti-infectious properties of vascular graft coatings was defined.

Effectiveness of perioperative pain science education on pain, psychological factors and physical functioning: A systematic review.

OBJECTIVE: To synthesize the evidence on the effectiveness of pain science education on pain, psychological factors and physical functioning in adults who underwent surgery. DATA SOURCES: A systematic literature search of English articles using PubMed/Medline, Embase, Web of Science Core Collection, and Cochrane Library. REVIEW METHODS: The search strategy was constructed as follows: (((pain) AND (education)) OR (pain education)) AND (surgery). Only controlled quantitative studies in adults reporting outcome(s) on pain, psychological factors and/or physical functioning were included. Risk of bias was assessed using the Cochrane risk of bias tools. P-values and corresponding effect sizes for interaction-effect (time × group) portrayed the difference in change over time between groups were of interest. The last search was conducted on February 28, 2021. RESULTS: Nine papers (n = 1078) were deemed eligible for this review. Two randomized controlled trials showed significant interaction effects. Breast cancer patients who had received one preoperative pain science education session showed a significant increase in postoperative pain compared to controls (P-value = 0.0394). Furthermore, psychological factors (pain catastrophizing and kinesiophobia) decreased in participants who had received pain science education before total knee arthroplasty, while this was not the case in the control group (P-value < 0.001, ƞ2p:0.11). CONCLUSIONS: Overall, pain science education did not result in any significant postoperative effects on pain, psychological factors and/or physical functioning compared to controls. There is currently no strong evidence for the implementation of pain science education in the perioperative period.Registration number: PROSPERO: ID 161267, registration number CRD42020161267.

Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline.

INTRODUCTION: Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS: Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.

The influence of duration of infection on outcome of debridement and implant retention in fracture-related infection.

AIMS: The principle strategies of fracture-related infection (FRI) treatment are debridement, antimicrobial therapy, and implant retention (DAIR) or debridement, antimicrobial therapy, and implant removal/exchange. Increasing the period between fracture fixation and FRI revision surgery is believed to be associated with higher failure rates after DAIR. However, a clear time-related cut-off has never been scientifically defined. This systematic review analyzed the influence of the interval between fracture fixation and FRI revision surgery on success rates after DAIR. METHODS: A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed (including MEDLINE), Embase, and Web of Science Core Collection, investigating the outcome after DAIR procedures of long bone FRIs in clinical studies published until January 2020. RESULTS: Six studies, comprising 276 patients, met the inclusion criteria. Data from this review showed that with a short duration of infection (up to three weeks) and under strict preconditions, retention of the implant is associated with high success rates of 86% to 100%. In delayed infections with a fracture fixation-FRI revision surgery interval of three to ten weeks, absence of recurrent infection was reported in 82% to 89%. Data on late FRIs, with a fracture fixation-FRI revision surgery interval of more than ten weeks, are scarce and a success rate of 67% was reported. CONCLUSION: Acute/early FRI, with a short duration of infection, can successfully be treated with DAIR up to ten weeks after osteosynthesis. The limited available data suggest that chronic/late onset FRI treated with DAIR may be associated with a higher rate of recurrence. Successful outcome is dependent on managing all aspects of the infection. Thus, time from fracture fixation is not the only factor that should be considered in treatment planning of FRI. Due to the heterogeneity of the available data, these conclusions have to be interpreted with caution. Cite this article: Bone Joint J 2021;103-B(2):213-221.

Accuracy of Tissue and Sonication Fluid Sampling for the Diagnosis of Fracture-Related Infection: A Systematic Review and Critical Appraisal.

Introduction: Intraoperatively obtained peri-implant tissue cultures remain the standard for diagnosis of fracture-related infection (FRI), although culture-negative cases may complicate treatment decisions. This paper reviews the evidence on sonication fluid and tissue sampling for the diagnosis of FRI. Methods: A comprehensive search in Pubmed, Embase and Web-of-Science was carried out on April 5, 2018, to identify diagnostic validation studies regarding sonication fluid and tissue sampling for FRI. Results: Out of 2624 studies, nine fulfilled the predefined inclusion criteria. Five studies focused on sonication fluid culture, two on PCR and two on histopathology. One additional histopathology study was found after screening of reference lists. There is limited evidence that sonication fluid culture may be a useful adjunct to conventional tissue culture, but no strong evidence that it is superior or can replace tissue culture. Regarding molecular techniques and histopathology the evidence is even less clear. Overall, studies had variable 'gold standard' criteria for comparison and poorly reported culture methods. Conclusions: Scientific evidence on sonication fluid and tissue sampling, including culture, molecular techniques and histopathology for the diagnosis of FRI is scarce. It is imperative that laboratory protocols become standardized and uniform diagnostic criteria, as recently published in a consensus definition, be implemented.

2BIC: taking your adventuring gear to organise pop-up health information literacy sessions.

Academic libraries play an important role in the provision of health information literacy (IL) skills and there are many approaches to how these can be delivered. In this paper, guest writers Inge Discart and colleagues from KU Leuven Libraries 2Bergen Information Centre (2BIC) in Belgium discuss a pop-up information literacy skills project. In particular, the article presents the findings from an initial information skills needs assessment conducted at the University, followed by how the concept of the pop-up sessions was developed and promoted throughout the organisation. The paper identifies the variety of sessions offered and the format in which they were delivered, with final results on how these were received and which sessions were the most popular. This article provides insight into an alternative approach to health information skills delivery and the outcomes from it. H S.

Autogenous transalveolar transplantation of maxillary canines: a systematic review and meta-analysis.

Background and objectives: The objective was to systematically review transalveolar transplantation of maxillary canines and the long-term outcome for an average follow-up period of 2 years or more. Data collection and analysis: A systematic review of the currently available literature until December 2017 was conducted, using Medline, Cochrane Central, Web off Science, and PubMed. Articles were screened for 1. indications, 2. contra-indications, 3. surgical planning, 4. surgical technique, 5. associated risk factors, and 6. long-term outcome for transalveolar transplantation of maxillary canines with the following outcome measures: bone-related outcomes, tooth-related outcomes, soft tissue-related outcomes, and aesthetic outcome measures. Descriptive statistics, as well as a quality assessment of included articles, were performed. Following study retrieval and selection, relevant data was extracted and the risk of bias was assessed using the Methodological index for non-randomized studies (MINORS). Results: Twelve articles were included in this review. These studies included outcome data for 783 autotransplanted maxillary canines, with long-term studies indicating a clinically acceptable overall outcome. Limitations: Since the lack of randomized controlled trials considering this topic, the quality of the evidence in the present review is considered low. However, impacted maxillary canines are a rare anomaly and different aspects, such as position of the impacted canine, patient's age and patient's demands, and expectancies must be taken into account, it is practically impossible to randomize treatment. Conclusions: There is sufficient evidence to justify the transalveolar transplantation of maxillary canines as a legitimate treatment technique for impacted maxillary canines deemed difficult to treat with surgical exposure and subsequent orthodontic alignment. Long-term studies have shown that a good overall outcome is to be expected. There is no clear agreement in the literature on the indications and contra-indications for transalveolar transplantation of maxillary canines. Implication of key findings: It is highly desirable that further research on this issue be undertaken, high-quality observational studies are recommended. Registration: PROSPERO (CRD42017056348).

Nondestructive measurement of fruit and vegetable quality.

We review nondestructive techniques for measuring internal and external quality attributes of fruit and vegetables, such as color, size and shape, flavor, texture, and absence of defects. The different techniques are organized according to their physical measurement principle. We first describe each technique and then list some examples. As many of these techniques rely on mathematical models and particular data processing methods, we discuss these where needed. We pay particular attention to techniques that can be implemented online in grading lines.

Detection of Pseudomonas aeruginosa in sputum headspace through volatile organic compound analysis.

INTRODUCTION: Chronic pulmonary infection is the hallmark of cystic fibrosis lung disease. Searching for faster and easier screening may lead to faster diagnosis and treatment of Pseudomonas aeruginosa (P. aeruginosa). Our aim was to analyze and build a model to predict the presence of P. aeruginosa in sputa. METHODS: Sputa from 28 bronchiectatic patients were used for bacterial culturing and analysis of volatile compounds by gas chromatography-mass spectrometry. Data analysis and model building were done by Partial Least Squares Regression Discriminant analysis (PLS-DA). Two analysis were performed: one comparing P. aeruginosa positive with negative cultures at study visit (PA model) and one comparing chronic colonization according to the Leeds criteria with P. aeruginosa negative patients (PACC model). RESULTS: The PA model prediction of P. aeruginosa presence was rather poor, with a high number of false positives and false negatives. On the other hand, the PACC model was stable and explained chronic P. aeruginosa presence for 95% with 4 PLS-DA factors, with a sensitivity of 100%, a positive predictive value of 86% and a negative predictive value of 100%. CONCLUSION: Our study shows the potential for building a prediction model for the presence of chronic P. aeruginosa based on volatiles from sputum.

Evaluation of fast volatile analysis for detection of Botrytis cinerea infections in strawberry.

Grey mold (Botrytis cinerea) is one of the major phytopathogens causing serious losses during strawberry postharvest and storage. B. cinerea-host interaction affect emissions of volatile compounds during infection resulting in a characteristic earthy, mushroom odor. Therefore, the objective of this study was to evaluate two analytical techniques based on fast volatile analysis on their performance for monitoring evolution and early detection of B. cinerea infections in strawberry. In a first experiment headspace multi-capillary column-ion mobility spectrometry (HS MCC-IMS) has been successfully used to evaluate development of strawberry aroma during shelflife. In a second experiment the same technique has been used to detect the degree of B. cinerea infection through changes in the volatile profile. Additionally, these samples were analyzed with headspace solid-phase-microextraction fast GC-MS (HS SPME fast GC-MS). Both HS MCC-IMS and HS SPME fast GC-MS could determine the changes in volatile composition as a function of the degree of B. cinerea infection as determined by an enzyme-linked immunosorbent assay (ELISA) and could be used to follow the evolution of infection. According to the ELISA data, some fruit were infected even without any symptoms and volatiles produced by the fungus may be overshadowed by the fruit volatiles. Therefore, both analytical techniques could not be used for early detection of B. cinerea infections. After identification of the volatile compounds and multivariate data analysis, potential biomarkers specific for B. cinerea were highlighted, being 3-methylbutanal, cis-4-decenal, 2-methyl-1-butanol, 2-methyl-1-propanol, 1-octen-3-one and 1-octen-3-ol.

Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): the first member of a new κ-KTX subfamily.

Given their medical importance, most attention has been paid toward the venom composition of scorpions of the Buthidae family. Nevertheless, research has shown that the venom of scorpions of other families is also a remarkable source of unique peptidyl toxins. The κ-KTx family of voltage-gated potassium channel (VGPC) scorpion toxins is hereof an example. From the telson of the scorpion Heterometrus laoticus (Scorpionidae), a peptide, HelaTx1, with unique primary sequence was purified through HPLC and sequenced by Edman degradation. Based on the amino acid sequence, the peptide could be cloned and the cDNA sequence revealed. HelaTx1 was chemically synthesized and functionally characterized on VGPCs of the Shaker-related, Shab-related, Shaw-related and Shal-related subfamilies. Furthermore, the toxin was also tested on small- and intermediate conductance Ca(2+)-activated K(+) channels. From the channels studied, K(v)1.1 and K(v)1.6 were found to be the most sensitive (K(v)1.1 EC(50)=9.9±1.6 µM). The toxin did not alter the activation of the channels. Competition experiments with TEA showed that the toxin is a pore blocker. Mutational studies showed that the residues E353 and Y379 in the pore of K(v)1.1 act as major interaction points for binding of the toxin. Given the amino acid sequence, the predicted secondary structure and the biological activity on VGPCs, HelaTx1 should be included in the κ-KTX family. Based on a phylogenetic study, we rearranged this family of VGPC toxins into five subfamilies and suggest that HelaTx1 is the first member of the new κ-KTx5 subfamily.

Isolation and characterization of two novel scorpion toxins: The alpha-toxin-like CeII8, specific for Na(v)1.7 channels and the classical anti-mammalian CeII9, specific for Na(v)1.4 channels.

Scorpion beta-toxins represent a particular pharmacological group of voltage-gated sodium channel (VGSC) neurotoxins. They typically shift the voltage dependence of activation to more hyperpolarizing potentials and reduce the peak current amplitude by binding to receptor-site 4. Here, we report the purification and functional characterization of the first voltage-gated sodium channel toxins, CeII8 and CeII9, isolated from the scorpion Centruroides elegans (Thorell, 1876), which is responsible for deadly cases of intoxication in Mexico. The soluble venom was fractionated by gel filtration and ion-exchange chromatography, followed by reversed-phase HPLC. The toxins CeII8 and CeII9 were further purified and both their amino acid sequence and molecular weight were determined. Both toxins were electrophysiologically characterized on four mammalian VGSCs (rNa(v)1.2, rNa(v)1.4, hNa(v)1.5 and rNa(v)1.7) expressed heterologously in Xenopus laevis oocytes, using the two-electrode voltage-clamp technique. Although CeII8 has the highest sequence similarity with scorpion alpha-toxins, inhibiting the inactivation of VGSCs, 300 nM toxin had a clear beta-toxin effect and was selective towards Na(v)1.7, involved in short-term and inflammatory pain. To the best of our knowledge, CeII8 is the first beta-toxin active on Na(v)1.7. CeII9, a typical anti-mammalian beta-toxin, selectively modulated Na(v)1.4 at a concentration of 700 nM and was, in contrast to CeII8, found to be lethal to mice. Interestingly, both toxins, despite their differences in amino acid sequence, only altered the biophysical properties of a fraction of the expressed sodium channels. Since these effects have also been reported for the beta-toxin CssIV, the bioactive surfaces of the toxins have been compared to each other.

OdK2, a Kv1.3 channel-selective toxin from the venom of the Iranian scorpion Odonthobuthus doriae.

The first Kv1.3 channel-selective toxin from the venom of the Iranian scorpion Odonthobuthus doriae (OdK2) was purified, sequenced and characterized physiologically. OdK2 consists of 38 amino acids, including six conserved cysteine and a C-terminal lysine residue, as revealed by the unique use of a quadrupole ion cyclotron resonance Fourier-transform mass spectrometer. Based on multiple sequence alignments, OdK2 was classified as alpha-KTX3.11. The pharmacological effects of OdK2 were studied on a panel of eight different cloned K(+) channels (vertebrate Kv1.1-Kv1.6, Shaker IR and hERG) expressed in Xenopus laevis oocytes. Interestingly, OdK2 selectively inhibits the currents through Kv1.3 channels with an IC50 value of 7.2+/-2.7nM.