Pushing the Frontiers of Biodiversity Research: Unveiling the Global Diversity, Distribution, and Conservation of Fungi

Fungi comprise approximately 20% of all eukaryotic species and are connected to virtually all life forms on Earth. Yet, their diversity remains contentious, their distribution elusive, and their conservation neglected. We aim to flip this situation by synthesizing current knowledge. We present a revised estimate of 2–3 million fungal species with a “best estimate” at 2.5 million. To name the unknown >90% of these by the end of this century, we propose recognition of species known only from DNA data and call for large-scale sampling campaigns. We present an updated global map of fungal richness, highlighting tropical and temperate ecoregions of high diversity. We call for further Red List assessments and enhanced management guidelines to aid fungal conservation. Given that fungi play an inseparable role in our lives and in all ecosystems, and considering the fascinating questions remaining to be answered, we argue that fungi constitute the next frontier of biodiversity research

Coronary artery height differences and their effect on fractional flow reserve

Background: Fractional flow reserve (FFR) uses pressure-based measurements to assess the severityof a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximalaortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, mayimpact FFR calculation.Methods: One hundred computed tomography coronary angiographies were used to measure heightdifferences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. Thiswas tested in a simulation of intermediate coronary stenosis to give the “corrected FFR” (cFFR) andpercentage of values, which crossed a threshold of 0.8.Results: The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm,distal circumflex (Cx) –3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV)–5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, –0.027 in the Cx, –0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatmentthreshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases.Conclusions: There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values

Recovery of Absolute Coronary Blood Flow and Microvascular Resistance After Chronic Total Occlusion Percutaneous Coronary Intervention: An Exploratory Study

Background: This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results: In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short‐term follow‐up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow‐up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow‐up (P<0.001). In agreement, absolute resistance in the myocardial territory perfused by the CTO artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow‐up (P=0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow‐up. Positive remodeling of the distal CTO vessel with an increase in lumen diameter was observed. Conclusions: After successful CTO PCI, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time

Assessing the burden of paediatric influenza in Europe: the European Paediatric Influenza Analysis (EPIA) project

The European Paediatric Influenza Analysis (EPIA) project is a multi-country project that was created to collect, analyse and present data regarding the paediatric influenza burden in European countries, with the purpose of providing the necessary information to make evidence-based decisions regarding influenza immunisation recommendations for children. The initial approach taken is based on existing weekly virological and age-specific influenza-like illness (ILI) data from surveillance networks across Europe. We use a multiple regression model guided by longitudinal weekly patterns of influenza virus to attribute the weekly ILI consultation incidence pattern to each influenza (sub)type, while controlling for the effect of respiratory syncytial virus (RSV) epidemics. Modelling the ILI consultation incidence during 2002/2003–2008 revealed that influenza infections that presented for medical attention as ILI affected between 0.3% and 9.8% of children aged 0–4 and 5–14 years in England, Italy, The Netherlands and Spain in an average season. With the exception of Spain, these rates were always higher in children aged 0–4 years. Across the six seasons analysed (five seasons were analysed from the Italian data), the model attributed 47–83% of the ILI burden in primary care to influenza virus infection in the various countries, with the A(H3N2) virus playing the most important role, followed by influenza viruses B and A(H1N1). National season averages from the four countries studied indicated that between 0.4% and 18% of children consulted a physician for ILI, with the percentage depending on the country and health care system. Influenza virus infections explained the majority of paediatric ILI consultations in all countries. The next step will be to apply the EPIA modelling approach to severe outcomes indicators (i.e. hospitalisations and mortality data) to generate a complete range of mild and severe influenza burden estimates needed for decision making concerning paediatric influenza vaccination

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial

Background: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. Findings: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy

Health status of adults with Short Stature: A comparison with the normal population and one well-known chronic disease (Rheumatoid Arthritis)

BACKGROUND: To examine the subjective health status of adults with short stature (ShSt) and compare with the general population (GP) and one well-known chronic disease, rheumatoid artritis (RA). In addition, to explore the association between age, gender, height, educational level and different aspects of health status of adults with short stature. METHODS: A questionnaire was mailed to 72 subjects with short stature registered in the database of a Norwegian resource centre for rare disorders, response rate 61% (n = 44, age 16–61). Health status was assessed with SF-36 version 2. Comparison was done with age and gender matched samples from the general population in Norway (n = 264) and from subjects with RA (n = 88). RESULTS: The ShSt sample reported statistically significant impaired health status in all SF-36 subscales compared with the GP sample, most in the physical functioning, Mean Difference (MD) 34 (95% Confidence Interval (CI) 25–44). The ShSt reported poorer health status in mental health, MD 11 (95% CI 4–18) and social functioning, MD 11 (95% CI 2–20) but better in role physical MD 13 (95% CI 1–25) than the RA sample. On the other subscales there were minor difference between the ShSt and the RA sample. Within the short stature group there was a significant association between age and all SF-36 physical subcales, height was significantly associated with physical functioning while level of education was significantly associated with mental health. CONCLUSION: People with short stature reported impaired health status in all SF-36 subscales indicating that they have health problems that influence their daily living. Health status seems to decline with increasing age, and earlier than in the general population

Solution-focused intervention for sick listed employees with psychological problems or muscle skeletal pain: a randomised controlled trial [ISRCTN39140363]

BACKGROUND: Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years. In the current study we assess the efficacy of a solution-focused follow-up for sick-listed employees. METHODS: Employees on long-term sick leave due to psychological problems or muscle skeletal pain (n = 703) were invited to participate in the project. Following self-recruitment, 103 were randomly allocated to receive solution-focused follow-up (n = 53) or "treatment as usual" (n = 50). The intervention was integrated within the regular follow up of six social security offices and organised as eight weekly solution focused work sessions. Effectiveness was measured by rate of return to work and health related quality of life (SF-36). RESULTS: Intention to treat analysis showed no significant differences between the two groups for any of the outcome measures. Secondary analysis, comparing those who attended at least 50% of the sessions with the control group revealed a significant difference in favour of the active intervention group in the SF-36 subscale of mental health (Effect Size 0.56, p = 0.05). When comparing the subgroup of participants with psychological problems there was a significant difference in mental health in favour of the intervention group (Effect Size 0.71, p = 0.041). CONCLUSION: A voluntary solution-focused intervention offered by social-security offices is no more effective than regular follow up for employees on long-term sick leave due to psychological problems or muscle skeletal pain

The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol

BackgroundPercutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated.AimsThe ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3.MethodsPatients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up.ResultsThe co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test.ConclusionThe feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's

Impact of point-of-care pre-procedure creatinine and eGFR testing in patients with ST segment elevation myocardial infarction undergoing primary PCI: The pilot STATCREAT study

Background: Contrast-induced acute kidney injury (CI-AKI) is a recognised complication during primary PCI that affects short and long term prognosis. The aim of this study was to assess the impact of point-of-care (POC) pre-PPCI creatinine and eGFR testing in STEMI patients. Methods 160 STEMI patients (STATCREAT group) with pre-procedure POC testing of Cr and eGFR were compared with 294 consecutive retrospective STEMI patients (control group). Patients were further divided into subjects with or without pre-existing CKD. Results: The incidence of CI-AKI in the whole population was 14.5% and not different between the two overall groups. For patients with pre-procedure CKD, contrast dose was significantly reduced in the STATCREAT group (124.6 ml vs. 152.3 ml, p = 0.015). The incidence of CI-AKI was 5.9% (n = 2) in the STATCREAT group compared with 17.9% (n = 10) in the control group (p = 0.12). There was no difference in the number of lesions treated (1.118 vs. 1.196, p = 0.643) or stents used (1.176 vs. 1.250, p = 0.78). For non-CKD patients, there was no significant difference in contrast dose (172.4 ml vs. 158.4 ml, p = 0.067), CI-AKI incidence (16.7% vs. 13.4%, p = 0.4), treated lesions (1.167 vs. 1.164, p = 1.0) or stents used (1.214 vs. 1.168, p = 0.611) between the two groups. Conclusions: Pre-PPCI point-of-care renal function testing did not reduce the incidence of CI-AKI in the overall group of STEMI patients. In patients with CKD, contrast dose was significantly reduced, but a numerical reduction in CI-AKI was not found to be statistically significant. No significant differences were found in the non-CKD group

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)