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Biological particles suspended in the atmosphere have a crucial role in the dynamics of the biosphere underneath. Although much attention is paid for the chemical and physical properties of these particles, their biological taxonomic identity, which is relevant for ecological research, remains little studied. We took air samples at 300 meters above the forest in central Amazonia, in seven periods of 7 days, and used high-throughput DNA sequencing techniques to taxonomically identify airborne fungal and plant material. The use of a molecular identification technique improved taxonomic resolution when compared to morphological identification. This first appraisal of airborne diversity showed that fungal composition was strikingly different from what has been recorded in anthropogenic regions. For instance, basidiospores reached 30% of the OTUs instead of 3–5% as found in the literature; and the orders Capnodiales and Eurotiales—to which many allergenic fungi and crop pathogens belong—were much less frequently recorded than Pleosporales, Polyporales, and Agaricales. Plant OTUs corresponded mainly to Amazonian taxa frequently present in pollen records such as the genera Helicostilys and Cecropia and/or very abundant in the region such as Pourouma and Pouteria. The origin of extra-Amazonian plant material is unknown, but they belong to genera of predominantly wind-pollinated angiosperm families such as Poaceae and Betulaceae. Finally, the detection of two bryophyte genera feeds the debate about the role of long distance dispersal in the distribution of these plants.

Abstract We assessed soil fungal diversity at two sites on Deception Island, South Shetland Islands, Antarctica using DNA metabarcoding analysis. The first site was a relatively undisturbed area, and the second was much more heavily impacted by research and tourism. We detected 346 fungal amplicon sequence variants dominated by the phyla Ascomycota, Basidiomycota, Mortierellomycota and Chytridiomycota. We also detected taxa belonging to the rare phyla Mucoromycota and Rozellomycota, which have been difficult to detect in Antarctica by traditional isolation methods. Cladosporium sp., Pseudogymnoascus roseus, Leotiomycetes sp. 2, Penicillium sp., Mortierella sp. 1, Mortierella sp. 2, Pseudogymnoascus appendiculatus and Pseudogymnoascus sp. were the most dominant fungi. In addition, 440,153 of the total of 1,214,875 reads detected could be classified only at the level of Fungi. In both sampling areas the DNA of opportunistic, phytopathogenic and symbiotic fungi were detected, which might have been introduced by human activities, transported by birds or wind, and/or represent resident fungi not previously reported from Antarctica. Further long-term studies are required to elucidate how biological colonization in the island may be affected by climatic changes and/or other anthropogenic influences.

Abstract Lorentziella imbricata (Mitt.) Broth. belongs to the family Gigaspermaceae and is a common plant in the subtropical regions of the Noth and South America. This plant can be characterized by presenting leafy stems arising from subterranean rhizomatous axes, pale green or often whitish leaves, and sessile large capsules with large spores. This is the first citation of the genus Lorentziella and the family Gigaspermaceae for Brazil, found during field collections in the Pampa biome, state of Rio Grande do Sul.

In the course of a multi-taxon biodiversity inventory for the island of St. Eustatius, lichens were collected from 11 plots representing different vegetation types. From these collections, 126 lichen species are reported, 54 of which are new reports for St. Eustatius. Most species could be identified to species level based on morphological and chemical characters. In a few cases, mtSSU DNA sequences were generated for a preliminary molecular identification and future phylogenetic studies. In total, 263 identified lichen species are currently known from St. Eustatius, as well as some additional genera with yet unidentified species and lichenicolous fungi.

The development of evidence-based international strategies for the conservation and management of Arctic ecosystems in the face of climate change is hindered by critical knowledge gaps in Arctic floristic diversity and evolution. Particularly poorly studied are the bryophytes, which dominate the vegetation across vast areas of the Arctic and consequently play an important role in global biogeochemical cycles. Currently, much of what is known about Arctic floristic evolution is based on studies of vascular plants. Bryophytes, however, possess a number of features, such as poikilohydry, totipotency, several reproductive strategies, and the ability to disperse through microscopic diaspores, that may cause their responses to Arctic environments to differ from those of the vascular plants. Here we discuss several priority areas identified in the Arctic Council’s “Arctic Biodiversity Assessment” that are necessary to illuminate patterns of Arctic bryophyte evolution and diversity, including dispersal, glacial refugia, local adaptation, and ecological interactions with bryophyte-associated microbiomes. A survey of digitally available herbarium data archived in the largest online aggregate, GBIF, across the Arctic to boreal zones indicates that sampling coverage of mosses is heterogeneous and relatively sparse in the Arctic sensu stricto. A coordinated international effort across the Arctic will be necessary to address knowledge gaps in Arctic bryophyte diversity and evolution in the context of ongoing climate change.

Since the introduction of non-native rodents to the Caribbean region, these invaders have successfully occupied many, if not most, islands where they pose tremendous threats to native biodiversity and ecosystems. The objective of our study was to conduct a preliminary assessment of the relative abundance of invasive alien rodents in different vegetation types on the small Caribbean island of St. Eustatius, which has no native rodent species. We used tracking tunnels (baited ink cards placed in tunnels to identify the prints of animals lured to the card) to determine the presence of rodent species. We collected data in 25 × 25 m (n = 13) and 5 × 5 m (n = 130) plots to determine whether elevation, number of tree species, canopy cover or other microhabitat components were correlated with rodent relative abundance. Invasive rodents are present in varying relative abundances in rural areas on St. Eustatius. House mice (Mus musculus) were not recorded inside the terrestrial protected areas, whereas black rats (Rattus rattus) were detected in all elevations and all but one vegetation type sampled. We determined significant correlations between some of the habitat characteristics, especially elevation, canopy height, leaf litter cover and number of tree species, which showed significant collinearity with 27 of 45 pairwise comparisons. There was a significant correlation between rodent relative abundance and the number of tree species, but not between elevation, number of living trees, number of shrubs, rainfall, canopy cover, canopy height, leaf litter cover, leaf litter depth, or slope. There was a significant difference within vegetation types for the frequency of traps containing rat versus mouse tracks. Our study was impacted by two major hurricanes in September 2017. Keywords: Black rat, House mouse, Island, Relative abundance, Tracking tunnels, Vegetation

Caribbean dry forests are among the most endangered tropical ecosystems on earth. Several studies exist on their floristic composition and their recovery after natural or man-made disturbances, but little is known on the small Dutch Caribbean islands. In this study, we present quantitative data on plant species richness and abundance on St. Eustatius, one of the smallest islands of the Lesser Antilles. We collected and identified trees, shrubs, lianas and herbs in 11 plots of 25 x 25 m in different vegetation types. We compared their floristic composition and structure to vegetation surveys from roughly the same locations in the 1990s and 1950s. We found substantial differences among our 11 plots: vegetation types varied from evergreen forests to deciduous shrubland and open woodland. The number of tree species ≥10 cm DBH ranged between one and 17, and their density between three and 82 per plot. In spite that all plots were subject to grazing by free roaming cattle, canopy height and floristic diversity have increased in the last decades. Invasive species are present in the open vegetation types, but not under (partly) closed canopy. Comparison with the earlier surveys showed that the decline of agriculture and conservation efforts resulted in the regeneration of dry forests between the 1950s and 2015. This process has also been reported from nearby islands and offers good opportunities for the future conservation of Caribbean dry forests.

From glacial reconstructions it is clear that Antarctic terrestrial life must have been extremely limited throughout Quaternary glacial periods. In contrast, recent biological studies provide clear evidence for long-term in situ persistence throughout glacial times within most extant Antarctic faunal and several microbial groups. However, even now, the evolutionary history of the Antarctic flora—despite playing major role in Antarctic ecosystems—remains poorly studied. We assessed the diversity, richness and relative age divergences within Schistidium (Grimmiaceae, Bryophyta), the most species-rich plant genus in the Antarctic, as well as the plant genus containing most Antarctic endemic species. We applied phylogenetic and molecular dating methods based on nuclear ribosomal Internal Transcribed Spacer sequences, including all known Antarctic Schistidium species with available sample material. We additionally investigated the continent-wide genetic diversity within the most common Antarctic representative of the genus—the endemic species Schistidium antarctici—and performed preliminary phylogeographic analyses of the bipolar species Schistidium rivulare. Most previously described Antarctic Schistidium species were genetically distinct, confirming their specific status. Interspecific divergences of all species took place at least ~1 Mya, suggesting a likely in situ persistence in Antarctica for (at least) all endemic Schistidium species. The widespread endemic species, Schistidium antarctici, diverged from other Antarctic congeners in the late Miocene, thereby revealing the oldest extant plant species currently known in Antarctica, and providing increasing support for the hypothesis of vegetation survival through multiple glacial periods. Within S. antarctici we identified several distinct clades dividing the eastern Antarctic Peninsula and Scotia Arc islands from the western Antarctic Peninsula and all continental locations. This suggests that the mountainous spine on the Antarctic Peninsula forms a strong barrier to gene flow in this species, while increased genetic diversity in the northern Maritime Antarctic indicates likely glacial refugia in this area. This study provides an important first step toward assessing the diversity and evolutionary history of the most speciose moss genus in the Antarctic. The multi-million year presence of several endemic species contributes to studies on their adaptive potential to survive climate change over both historical and contemporary timescales.

In bryophytes a morphological species concept is still most commonly employed, but delimitation of closely related species based on morphological characters is often difficult. Here we test morphological species circumscriptions in a species complex of the moss genus Racomitrium, the R. canescens complex, based on variable DNA sequence markers from the plastid (rps4-trnT-trnL region) and nuclear (nrITS) genomes. The extensive morphological variability within the complex has led to different opinions about the number of species and intraspecific taxa to be distinguished. Molecular phylogenetic reconstructions allowed to clearly distinguish all eight currently recognised species of the complex plus a ninth species that was inferred to belong to the complex in earlier molecular analyses. The taxonomic significance of intraspecific sequence variation is discussed. The present molecular data do not support the division of the R. canescens complex into two groups of species (subsections or sections). Most morphological characters, albeit being in part difficult to apply, are reliable for species identification in the R. canescens complex. However, misidentification of collections that were morphologically intermediate between species questioned the suitability of leaf shape as diagnostic character. Four partitions of the molecular markers (rps4-trnT, trnT-trnL, ITS1, ITS2) that could potentially be used for molecular species identification (DNA barcoding) performed almost equally well concerning amplification and sequencing success. Of these, ITS1 provided the highest species discrimination capacity and should be considered as a DNA barcoding marker for mosses, especially in complexes of closely related species. Molecular species identification should be complemented by redefining morphological characters, to develop a set of easy-to-use molecular and non-molecular identification tools for improving biodiversity assessments and ecological research including mosses.

BackgroundLejeunea is a largely epiphytic, subcosmopolitan liverwort genus with a complex taxonomic history. Species circumscriptions and their relationships are subject to controversy; biogeographic history and diversification through time are largely unknown.Methodology and resultsWe employed sequences of two chloroplast regions (trnL-trnF, rbcL) and the nuclear ribosomal ITS region of 332 accessions to explore the phylogeny of the Harpalejeunea-Lejeunea-Microlejeunea complex. Lejeunea forms a well-supported clade that splits into two main lineages corresponding to L. subg. Lejeunea and L. subg. Crossotolejeunea. Neotropical accessions dominate early diverging lineages of both main clades of Lejeunea. This pattern suggests an origin in the Neotropics followed by several colonizations from the Neotropics into the Paleotropics and vice versa. Most Afro-Madagascan clades are related to Asian clades. Several temperate Lejeunea radiations were detected. Eighty two of the 91 investigated Lejeunea species could be identified to species level. Of these 82 species, 54 were represented by multiple accessions (25 para- or polyphyletic, 29 monophyletic). Twenty nine of the 36 investigated species of L. subg. Lejeunea were monoicous and 7 dioicous. Within L. subg. Crossotolejeunea, 15 of the 46 investigated species were monoicous and 31 dioicous. Some dioicous as well as some monoicous species have disjunct ranges.Conclusions/significanceWe present the first global phylogeny of Lejeunea and the first example of a Neotropical origin of a Pantropical liverwort genus. Furthermore, we provide evidence for the Neotropics as a cradle of Lejeunea lineages and detect post-colonization radiations in Asia, Australasia, Afro-Madagascar and Europe. Dioicy/monoicy shifts are likely non-randomly distributed. The presented phylogeny points to the need of integrative taxonomical studies to clarify many Lejeunea binomials. Most importantly, it provides a framework for future studies on the diversification of this lineage in space and time, especially in the context of sexual systems in Lejeuneaceae.

Purpose: Post-operative complications following emergency abdominal surgery are associated with significant morbidity and mortality. Despite the knowledge of prognostic factors associated with poor surgical outcomes; few have described risks of poor outcomes based on admission information in acute surgical setting. We aimed to derive a simple, point-of-care risk scale that predicts adults with increased risk of poor outcomes. Methods: We used data from an international multi-centre prospective cohort study. The effect of characteristics; age, hypoalbuminaemia, anaemia, renal insufficiency and polypharmacy on 90-day mortality was examined using fully adjusted multivariable models. For our secondary outcome we aimed to test whether these characteristics could be combined to predict poor outcomes in adults undergoing emergency general surgery. Subsequently, the impact of incremental increase in derived SHARP score on outcomes was assessed. Results: The cohort consisted of 419 adult patients between the ages of 16–94 years (median 52; IQR(39) consecutively admitted to five emergency general surgical units across the United Kingdom and one in Ghent, Belgium. In fully adjusted models the aforementioned characteristics; were associated with 90-day mortality. SHARP score was associated with higher odds of mortality in adults who underwent emergency general surgery, with a SHARP score of five also being associated with an increased length of hospital stay. Conclusions: SHARP risk score is a simple prognostic tool, using point-of-care information to predict poor outcomes in patients undergoing emergency general surgery. This information may be used to improve management plans and aid clinicians in delivering more person-centred care. Further validation studies are required to prove its utility.

Background: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. Results: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62–83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01–2.88 (14-day mortality). There also appeared to be a dose–response relationship. Conclusion: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. Plain Language Summary Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.

Objective: During the COVID-19 pandemic the continuation or cessation of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) has been contentious. Mechanisms have been proposed for both beneficial and detrimental effects. Recent studies have focused on mortality with no literature having examined length of hospital stay. The aim of this study was to determine the influence of ACEi and ARBs on COVID-19 mortality and length of hospital stay. Methods: COPE (COVID-19 in Older People) is a multicenter observational study including adults of all ages admitted with either laboratory or clinically confirmed COVID-19. Routinely generated hospital data were collected. Primary outcome: mortality; secondary outcomes: Day-7 mortality and length of hospital stay. A mixed-effects multivariable Cox’s proportional baseline hazards model and logistic equivalent were used. Results: 1371 patients were included from eleven centres between 27th February to 25th April 2020. Median age was 74 years [IQR 61–83]. 28.6% of patients were taking an ACEi or ARB. There was no effect of ACEi or ARB on inpatient mortality (aHR = 0.85, 95%CI 0.65–1.11). For those prescribed an ACEi or ARB, hospital stay was significantly reduced (aHR = 1.25, 95%CI 1.02–1.54, p = 0.03) and in those with hypertension the effect was stronger (aHR = 1.39, 95%CI 1.09–1.77, p = 0.007). Conclusions: Patients and clinicians can be reassured that prescription of an ACEi or ARB at the time of COVID-19 diagnosis is not harmful. The benefit of prescription of an ACEi or ARB in reducing hospital stay is a new finding.

Introduction This protocol describes an observational study which set out to assess whether frailty and/or multimorbidity correlates with short-term and medium-term outcomes in patients diagnosed with COVID-19 in a European, multicentre setting.Methods and analysis Over a 3-month period we aim to recruit a minimum of 500 patients across 10 hospital sites, collecting baseline data including: patient demographics; presence of comorbidities; relevant blood tests on admission; prescription of ACE inhibitors/angiotensin receptor blockers/non-steroidal anti-inflammatory drugs/immunosuppressants; smoking status; Clinical Frailty Score (CFS); length of hospital stay; mortality and readmission. All patients receiving inpatient hospital care >18 years who receive a diagnosis of COVID-19 are eligible for inclusion. Long-term follow-up at 6 and 12 months is planned. This will assess frailty, quality of life and medical complications.Our primary analysis will be short-term and long-term mortality by CFS, adjusted for age (18–64, 65–80 and >80) and gender. We will carry out a secondary analysis of the primary outcome by including additional clinical mediators which are determined statistically important using a likelihood ratio test. All analyses will be presented as crude and adjusted HR and OR with associated 95% CIs and p values.Ethics and dissemination This study has been registered, reviewed and approved by the following: Health Research Authority (20/HRA1898); Ethics Committee of Hospital Policlinico Modena, Italy (369/2020/OSS/AOUMO); Health and Care Research Permissions Service, Wales; and NHS Research Scotland Permissions Co-ordinating Centre, Scotland. All participating units obtained approval from their local Research and Development department consistent with the guidance from their relevant national organisation.Data will be reported as a whole cohort. This project will be submitted for presentation at a national or international surgical and geriatric conference. Manuscript(s) will be prepared following the close of the project.

Summary: Background: The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. Methods: This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). Findings: Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. Interpretation: In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19. Funding: None.

Plastid trnT?F and atpB?rbcL spacer sequences as well as AFLP fingerprints are utilised to infer phylogenetic relationships of Dendroligotrichum and Polytrichadelphus taxa (Polytrichaceae) in the palaeoaustral region. Phylogenies based on DNA sequence data support the monophyly of each genus. Relationships within Dendroligotrichum remain ambiguous owing to low sequence divergence. AFLP fingerprinting, however, allows a clear distinction of all included Dendroligotrichum and Polytrichadelphus taxa at the species level. The morphological, distributional, ecological and molecular differences justify the recognition of the following three species in Dendroligotrichum: D. dendroides (Brid. ex Hedw.) Broth. and D. squamosum (Hook.f. & Wilson) Cardot in southern South America, as well as D. microdendron (Mll. Hal.) G.L.Sm. in New Zealand; and the following two species in Polytrichadelphus: P. magellanicus (Hedw.) Mitt. s.str. in southern South America and P. innovans (Mll. Hal.) A.Jger in Australia and New Zealand. For Polytrichadelphus, the molecular topologies correspond with a vicariance scenario, with a basic split of taxa in the palaeoaustral region followed by migration of southern South American taxa northwards into the Neotropics. In Dendroligotrichum, substitutions and indels in the trnL intron and atpB?rbcL spacer are ambiguous in supporting either a basic split between the South American species and D. microdendron, similar to the one in Polytrichadelphus, or a trans-oceanic dispersal event between New Zealand and southern South America. [ABSTRACT FROM AUTHOR]

Introduction The incidence of thyroid cancer has increased worldwide, whether a real or apparent increase is debated. Literature from the USA suggests greater diagnostic scrutiny, environmental and genetic factors may all play a part. This increase will result in a greater number of referrals for surgical assessment. This study examined the trend in incidence of thyroid cancer in England and Wales. Materials and Methods A retrospective study, using the HES database over the period 2000-2010. Data were extracted of all newly diagnosed thyroid cancers in England and Wales and the age at diagnosis. Data were examined for the change in incidence of thyroid cancer diagnosis dependent on the age group of the patient using the linear regression model. Results 45411 patients were identified. In England the incidence of thyroid cancer rose from 5.7/100,000 of the population in 2000 to 9.9/100,000 in 2010 and in Wales it rose from 3.5/100,000 in 2000 to 7.5/100,000. There was a statistical increase (P≤0.02) (t-stat >2) in the diagnosis of thyroid cancers across all age groups with exception of the 0-14 age group (P>0.5). Conclusion There has been a statistical increase in the incidence of thyroid cancer. This is likely to impact on hospitals and cancer service resources. An increase in surgical demand and the coinciding ageing population highlights the importance of further investigation into the etiology, use of imaging, patient demographics, histology and overall mortality of this patient group.

Bermekimab is a true human monoclonal antibody that targets interleukin-1alpa (IL-1α), an inflammation-mediating alarmin. IL-1 receptor antagonist (IL-1Ra) is a natural molecule that blocks IL-1α activity by occupying the IL-1 receptor. The effect of endogenous IL-1Ra levels on the effectiveness of bermekimab is unknown. We investigated whether pre-treatment levels of circulating IL-1Ra, assessed by an enzyme-linked immunoassay, correlated with achievement of the primary outcome endpoint (effect on lean body mass and symptoms at week 8) in a Phase III study (2:1 randomization) of bermekimab versus placebo (each with best supportive care) in advanced colorectal cancer. Patients who responded to bermekimab in terms of achieving the primary endpoint had lower levels of IL-1Ra than non-responders (N = 204 patients; median = 843 vs. 1035 pg/ml, p=0.0092); no such relationship was observed in the placebo arm (N = 100 patients; 901 vs. 984 pg/ml, p = 0.55). Multivariate analysis corroborated that, in the bermekimab group, patients with lower baseline IL-1Ra levels were more likely to achieve the primary endpoint (odds ratio (OR) 1.7 (95% confidence interval (CI), 1.1 to 2.6), p = 0.017); in contrast, in the placebo arm, pre-treatment plasma IL-1Ra levels were not associated with outcome (OR 1.2 (95% CI 0.6 to 2.5), p = 0.57). The current findings demonstrate that, in a randomized phase III trial, patients with advanced colorectal cancer and lower levels of circulating IL-1Ra are more responsive to treatment with the IL-1α-targeting antibody bermekimab and these observations define a potential biomarker for anti-IL-1α therapy.

A 42-year-old man arrived at the emergency department in severe respiratory distress, requiring immediate intubation and ventilation. An emergency computed tomography (CT) neck scan identified a substantial haematoma within a multinodular goitre, necessitating an emergency total thyroidectomy. It was later discovered that the patient had been the victim of an assault involving blunt trauma to the anterior neck. Five days postoperatively the patient was extubated and was well enough to self-discharge the following day. Pathology revealed the lesion to be a ruptured follicular adenoma within his multinodular goitre. Signs of this rare but life-threatening condition may be subtle on initial presentation, particularly if the patient is obtunded. Patients with suspected blunt neck trauma should be observed for signs of respiratory distress. If this develops, the patient should be intubated to facilitate CT scan, and if thyroid haematoma is confirmed, emergency thyroidectomy is the definitive treatment.