Immunosuppression in stem cell clinical trials of neural and retinal cell types: A systematic review.

BACKGROUND: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments. OBJECTIVE: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells. METHODS: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool. RESULTS: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases. DISCUSSION: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon.

Parvodontia relampaga sp. nov.: A Cystostereaceae fungal pathogen that is the causal agent of relampago blight of woody plants in Florida, USA.

Starting in the fall of 2019, mortality, blight symptoms, and signs of white fungal mycelia were observed on external host tissues of non-native landscape trees as well as numerous native trees, understory shrubs, and vines throughout northern and central Florida, USA. We determined that the fungus is an undescribed species of Basidiomycota based on morphological characteristics and DNA sequence analysis. Phylogenetic analyses of the internal transcribed spacer (ITS), large subunit (LSU), and translation elongation factor 1-alpha (tef1) regions revealed that this novel plant pathogen is an undescribed taxon of the genus Parvodontia (Cystostereaceae, Agaricales). We propose the name Parvodontia relampaga sp. nov. which describes its unique morphological features and phylogenetic placement. We confirmed the pathogenicity of P. relampaga in greenhouse inoculations on host plants from which strains of this novel pathogen were isolated, including the non-native gymnosperm Afrocarpus falcatus, the non-native and commercially important Ligustrum japonicum, and the native tree Quercus hemisphaerica. P. relampaga was also detected on a total of 27 different species of woody host plants, including such economically and ecologically important hosts as Fraxinus, Ilex, Magnolia, Persea, Prunus, Salix, Vitis, and Vaccinium. For this new plant disease, we propose the name "relampago blight," which refers to the lightning-like rhizomorph growth (relámpago means 'lightning' in Spanish). This study presents a newly discovered fungal taxon with a wide host range on both angiosperms and gymnosperms that may be an emerging pathogen of concern in Florida and the Gulf Coast region.

Socioeconomic and ethnic disparities associated with access to cochlear implantation for severe-to-profound hearing loss: A multicentre observational study of UK adults.

BACKGROUND: Patients with severe-to-profound hearing loss may benefit from management with cochlear implants. These patients need a referral to a cochlear implant team for further assessment and possible surgery. The referral pathway may result in varied access to hearing healthcare. This study aimed to explore referral patterns and whether there were any socioeconomic or ethnic associations with the likelihood of referral. The primary outcome was to determine factors influencing referral for implant assessment. The secondary outcome was to identify factors impacting whether healthcare professionals had discussed the option of referral. METHODS AND FINDINGS: A multicentre multidisciplinary observational study was conducted in secondary care Otolaryngology and Audiology units in Great Britain. Adults fulfilling NICE (2019) audiometric criteria for implant assessment were identified over a 6-month period between 1 July and 31 December 2021. Patient- and site-specific characteristics were extracted. Multivariable binary logistic regression was employed to compare a range of factors influencing the likelihood of implant discussion and referral including patient-specific (demographics, past medical history, and degree of hearing loss) and site-specific factors (cochlear implant champion and whether the hospital performed implants). Hospitals across all 4 devolved nations of the UK were invited to participate, with data submitted from 36 urban hospitals across England, Scotland, and Wales. Nine hospitals (25%) conducted cochlear implant assessments. The majority of patients lived in England (n = 5,587, 86.2%); the rest lived in Wales (n = 419, 6.5%) and Scotland (n = 233, 3.6%). The mean patient age was 72 ± 19 years (mean ± standard deviation); 54% were male, and 75·3% of participants were white, 6·3% were Asian, 1·5% were black, 0·05% were mixed, and 4·6% were self-defined as a different ethnicity. Of 6,482 submitted patients meeting pure tone audiometric thresholds for cochlear implantation, 311 already had a cochlear implant. Of the remaining 6,171, 35.7% were informed they were eligible for an implant, but only 9.7% were referred for assessment. When adjusted for site- and patient-specific factors, stand-out findings included that adults were less likely to be referred if they lived in more deprived area decile within Indices of Multiple Deprivation (4th (odds ratio (OR): 2·19; 95% confidence interval (CI): [1·31, 3·66]; p = 0·002), 5th (2·02; [1·21, 3·38]; p = 0·05), 6th (2·32; [1·41, 3·83]; p = 0.05), and 8th (2·07; [1·25, 3·42]; p = 0·004)), lived in London (0·40; [0·29, 0·57]; p < 0·001), were male (females 1·52; [1·27, 1·81]; p < 0·001), or were older (0·97; [0·96, 0·97]; p < 0·001). They were less likely to be informed of their potential eligibility if they lived in more deprived areas (4th (1·99; [1·49, 2·66]; p < 0·001), 5th (1·75; [1·31, 2·33], p < 0·001), 6th (1·85; [1·39, 2·45]; p < 0·001), 7th (1·66; [1·25, 2·21]; p < 0·001), and 8th (1·74; [1·31, 2·31]; p < 0·001) deciles), the North of England or London (North 0·74; [0·62, 0·89]; p = 0·001; London 0·44; [0·35, 0·56]; p < 0·001), were of Asian or black ethnic backgrounds compared to white patients (Asian 0·58; [0·43, 0·79]; p < 0·001; black 0·56; [0·34, 0·92]; p = 0·021), were male (females 1·46; [1·31, 1·62]; p < 0·001), or were older (0·98; [0·98, 0·98]; p < 0·001). The study methodology was limited by its observational nature, reliance on accurate documentation of the referring service, and potential underrepresentation of certain demographic groups. CONCLUSIONS: The majority of adults meeting pure tone audiometric threshold criteria for cochlear implantation are currently not appropriately referred for assessment. There is scope to target underrepresented patient groups to improve referral rates. Future research should engage stakeholders to explore the reasons behind the disparities. Implementing straightforward measures, such as educational initiatives and automated pop-up tools for immediate identification, can help streamline the referral process.

Antibiotics versus non-antibiotic treatments for acute otitis externa: A systematic review and meta-analysis.

BACKGROUND: Otitis externa is a condition causing inflammation of the outer ear canal, which presents with itching, discharge and pain. Most cases of acute otitis externa are caused by bacterial infection and are thus treated with antibiotics. This systematic review and meta-analysis of randomised controlled trials aims to assess the effectiveness of topical non-antibiotic treatments compared to topical antibiotic treatment for the treatment of acute otitis externa. METHODS: Systematic review and meta-analysis databases searched: Cochrane Library including ClinicalTrials.gov; MEDLINE; World Health Organisation International Clinical Trials Registry Platform and Web of Science to identify randomised clinical trials evaluating topical antibiotics and topical non-antibiotic agents in adults and children with acute otitis externa. Non-antibiotic therapeutics for comparison with topical antibiotics included antiseptics, steroids, non-pharmaceuticals and astringents. RESULTS: Seventeen trials were eligible for inclusion, with 10 combined in meta-analysis. Data could be pooled comparing antiseptic and steroid monotherapies with topical antibiotic agents. There were no significant differences in cure rates in any pairwise comparisons. Individually, the majority of studies favoured topical antiseptics or steroids over antibiotics, however these differences were not significant when pooled in meta-analysis. CONCLUSION: Antiseptic, steroid and antibiotic monotherapies are all effective for the management of acute otitis externa. There is insufficient evidence to suggest that topical antiseptic or steroid agents are superior or inferior to topical antibiotics.

Changes in antimicrobial resistance in acute otitis media and otitis externa.

OBJECTIVES: Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial resistance, which is associated with treatment failure, morbidity, prolonged hospitalisation and mortality. This study aimed to identify longitudinal changes in microbiology and antimicrobial resistance in aural swabs taken from patients with AOM or OE. DESIGN: Retrospective observational analysis. SETTING: Aural samples processed at Manchester Medical Microbiology Partnership Laboratories between January 2008 and December 2018 were analysed to record organism isolated and antimicrobial sensitivity. PARTICIPANTS: Individual aural swabs from 7200 patients. MAIN OUTCOME MEASURES: Changes in the incidence of organisms and antimicrobial resistance between two time periods (2008-2012 and 2013-2018) were compared using the chi-squared test (alpha = 0.05). RESULTS: From 7200 swabs, 2879 (40%) were from children. The most frequently isolated organisms were Staphylococcus aureus (25%), Pseudomonas aeruginosa (24.4%), yeast (9.1%), mixed anaerobes (7.9%) and Haemophilus influenzae (6.1%). In children aged 0-4 years, H. influenzae had particularly high incidence (25%). Overall, the incidence of P. aeruginosa decreased significantly with time (p = 0.05). Isolates displaying resistance to one or more antimicrobial agents increased significantly in number in the second time period for P. aeruginosa (p = 0.04) and H. influenzae (p = 0.03). There was increased resistance to amoxicillin for P. aeruginosa (p = 0.01) and to erythromycin for H. influenzae (p < 0.01). CONCLUSION: Variations in type and frequency of organisms with increasing age likely result from differences in the preponderance of AOM compared to OE in children versus adults. We found increasing antimicrobial resistance for two organisms commonly isolated from AOM and OE infections, suggesting that aspects of current UK treatment practices and national recommendations may need to be revised.

Frequency of electrode migration after cochlear implantation in the early postoperative period. What are associated risk factors?

OBJECTIVES: To estimate the prevalence of, and risk factors associated with electrode migration (EM) in cochlear implant (CI) recipients. DESIGN: Historical cohort study of all CIs performed between 1 January 2018 and 1 August 2021 in a single tertiary adult and paediatric CI centre in the UK. MAIN OUTCOME MEASURES: The primary aim is to determine the prevalence of electrode migration, comparing intraoperative surgeon report and examination of a routine plain radiograph performed 2 weeks after surgery. EM is defined as the detection of movement of two or more electrodes out of the cochlea from the time of surgery. Multivariate analysis was performed to investigate preoperative and intraoperative risk factors that might predispose to migration. RESULTS: Four hundred and sixty-five patients, having 516 distinct surgeries, with 628 implants were analysed. EM occurred following 11.5% of implant operations. Pre-existing cochlear abnormality was an independent associated risk factor for EM (OR: 3.40 ⟨1.20-9.62⟩ p = .021). Demographics, surgical technique, usage of a precurved electrode, CSF leak, surgeon seniority and intraoperative telemetry did not influence risk of migration. There were 5 implants (0.8%) which migrated later than 2 weeks, with a median date of imaging diagnosis (x-ray or CT scan) of 263 days ⟨IQR:198⟩, for which head injury was a common precipitating factor. There were differences in the risk of migration between different lateral wall electrodes. CONCLUSION: EM in the early postoperative period is a common occurrence and is more likely in implant recipients with obstructed or malformed cochleae.

The Risk of Meningitis After Cochlear Implantation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to estimate the rate of postoperative meningitis (both immediate and long-term) in patients following cochlear implants (CIs). It aims to do so through a systematic review and meta-analysis of published studies tracking complications after CIs. DATA SOURCES: MEDLINE, Embase, and Cochrane Library. REVIEW METHODS: This review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies tracking complications following CIs in patients were included. Exclusion criteria included non-English language studies and case series reporting <10 patients. Bias risk was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed through DerSimonian and Laird random-effects models. RESULTS: A total of 116/1931 studies met the inclusion criteria and were included in the meta-analysis. Overall, there were 112 cases of meningitis in 58,940 patients after CIs. Meta-analysis estimated an overall rate of postoperative meningitis of 0.07% (95% confidence interval [CIs], 0.03%-0.1%; I2 = 55%). Subgroup meta-analysis showed this rate had 95% CIs crossing 0% in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, those with postoperative acute otitis media (AOM), and those implanted less than 5 years. CONCLUSION: Meningitis is a rare complication following CIs. Our estimated rates of meningitis after CIs appear lower than prior estimates based on epidemiological studies in the early 2000s. However, the rate still appears higher than the baseline rate in the general population. The risk was very low in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, received unilateral or bilateral implantations, developed AOM, those implanted with a round window or cochleostomy techniques, and those under 5 years.

Revising the taxonomic placement of Laetiporus persicinus within the Laetiporaceae.

The fungus currently known as Laetiporus persicinus is a recognizable brown-rot decayer that is widespread on oak hosts in the southeastern United States. This species was first described as Polyporus persicinus in 1872 based on collections by Henry W. Ravenel from South Carolina. In this study, we elucidate the phylogenetic relationships of Laetiporus persicinus based on maximum likelihood and Bayesian inference analyses of a four-locus data set (18S, 28S, rpb2, and tef1) from taxa within the Fomitopsidaceae and Laetiporaceae. The internal transcribed spacer (ITS) region was analyzed separately because it was not possible to align this locus across a diverse data set that included taxa from multiple families. Our analysis and previous studies indicate that Laetiporus persicinus does not belong to Laetiporus sensu stricto, and we found a strongly supported relationship between Laetiporus persicinus and the African species Kusaghiporia usambarensis, despite the fact that the 28S phylogeny resolved a different (but unsupported) topology. Here, we propose Kusaghiporia persicinus, comb. nov., based on a combination of morphological and molecular data. Laetiporus persicinus shares many morphological features with K. usambarensis that are missing in other Laetiporus species, including centrally stipitate basidiomata, a brown to pinkish pileus surface, and a pore layer that bruises when touched. However, K. usambarensis and L. persicinus differ in basidiospore size and shape as well as their geographic distributions. We provide a revised taxonomic treatment for this common wood-decay fungus.

Tuber eburneum and Tuber mujicii: New pine-associated Tuber species from eastern North America.

The ectomycorrhizal truffle genus Tuber is widespread and diverse. Recent sampling of ascomata, ectomycorrhizal root tips, and environmental sequences has resulted in the identification of many Tuber species that cannot be assigned to described species and require formal description. Using morphological and molecular phylogenetic analysis, we describe two North American Tuber species associated with pines (Pinus spp.). Tuber eburneum, sp. nov., is an early-diverging taxon in the Melanosporum clade that differs substantially from all other taxa in that clade due to its light-colored peridium and gleba, lack of peridial warts, and peridial hairs that are ornamented with small, irregular protrusions. Tuber mujicii, sp. nov., is a whitish truffle species in the Puberulum clade. Although T. mujicii is morphologically similar to many related taxa, it can be distinguished by a combination of characters, including peridium color, spore size, number of ascospores per ascus, and number of reticulations across the spore surface.

Cochlear Implantation in Neurofibromatosis Type 2: Experience From the UK Neurofibromatosis Type 2 Service.

OBJECTIVE: To review the outcomes of cochlear implants (CI) in patients with neurofibromatosis type 2 (NF2) in a large cohort, and identify factors associated with poor hearing benefit. STUDY DESIGN: Fifteen-year retrospective national observational case series. SETTING: United Kingdom regional NF2 multidisciplinary teams. PATIENTS: Consecutive patients with NF2 receiving a CI. INTERVENTIONS: CI for hearing rehabilitation. MAIN OUTCOME MEASURES: 1) Audiometric performance at 9 to 12 months after implantation using City University of New York (CUNY) sentence recognition score, and Bamford- Kowal-Bench (BKB) word recognition score in quiet (BKBq), and in noise (BKBn). 2) CI use at most recent review. RESULTS: Sixty four consecutive patients, median age 43 years, were included. Nine to 12 months mean audiometric scores were: CUNY 60.9%, BKBq 45.8%, BKBn 41.6%. There was no difference in audiometric outcomes between VS treatment modalities. At most recent review (median 3.6 years from implantation), 84.9% with device in situ/available data were full or part-time users. Between 9 and 12 months and most recent review there was an interval reduction in mean audiometric scores: CUNY -12.9%, BKBq -3.3%, BKBn -4.9%. Larger tumor size and shorter duration of profound hearing loss were the only variables associated with poorer audiometric scores. Tumor growth at the time of surgery was the only variable associated with CI non-use. Individual patient response was highly variable. CONCLUSIONS: CI can provide significant and sustained auditory benefits to patients with NF2 independent of tumor treatment modality, with the majority of those implanted becoming at least part-time users. Larger datasets are required to reliably assess the role of independent variables.

Acute paediatric mastoiditis in the UK before and during the COVID-19 pandemic: A national observational study.

OBJECTIVES: To explore the impact of COVID-19 on the management and outcomes of acute paediatric mastoiditis across the UK. DESIGN: National retrospective and prospective audit. SETTING: 48 UK secondary care ENT departments. PARTICIPANTS: Consecutive children aged 18 years or under, referred to ENT with a clinical diagnosis of mastoiditis. MAIN OUTCOME MEASURES: Cases were divided into Period 1 (01/11/19-15/03/20), before the UK population were instructed to reduce social contact, and Period 2 (16/03/20-30/04/21), following this. Periods 1 and 2 were compared for population variables, management and outcomes. Secondary analyses compared outcomes by primary treatment (medical/needle aspiration/surgical). RESULTS: 286 cases met criteria (median 4 per site, range 0-24). 9.4 cases were recorded per week in period 1 versus 2.0 in period 2, with no winter increase in cases in December 2020-Febraury 2021. Patient age differed between periods 1 and 2 (3.2 vs 4.7 years respectively, p < 0.001). 85% of children in period 2 were tested for COVID-19 with a single positive test. In period, 2 cases associated with P. aeruginosa significantly increased. 48.6% of children were scanned in period 1 vs 41.1% in period 2. Surgical management was used more frequently in period 1 (43.0% vs 24.3%, p = 0.001). Treatment success was high, with failure of initial management in 6.3%, and 30-day re-admission for recurrence in 2.1%. The adverse event rate (15.7% overall) did not vary by treatment modality or between periods 1& 2. CONCLUSION: The COVID-19 pandemic led to a significant change in the presentation and case mix of acute paediatric mastoiditis in the UK.

Molecular systematics and taxonomic overview of the bird's nest fungi (Nidulariaceae).

Fungi in the Nidulariaceae, otherwise known as 'bird's nest fungi', are among the least studied groups of Agaricomycetes (Basidiomycota). Bird's nest fungi are globally distributed and typically grow on woody debris or animal dung as saprotrophs. This group of fungi is morphologically diverse with ca. 200 described species. Phylogenetic relationships of bird's nest fungi were investigated with four commonly used loci (ITS, LSU, tef, and rpb2). The family was resolved as a monophyletic group with Squamanitaceae as a potential sister taxon. Cyathus and Crucibulum each formed its own independent and well-supported clade. Nidula and Nidularia formed a clade together, but each genus is polyphyletic. Two Mycocalia species included in our analyses were on their own separate branches, indicating that this genus is also polyphyletic. Misidentifications were detected in most genera, suggesting that species concepts need to be revisited and refined throughout Nidulariaceae. Several bird's nest fungi species have global geographical distributions whereas others may have more limited ranges. Basic morphological characters of bird's nest fungi have likely been lost or gained multiple times. The phylogenetic placement of Crucibulum is unclear and the sister lineage of bird's nest fungi is not conclusive. Further studies with data from rare species and additional informative genes are needed to fully resolve the topology of Nidulariaceae and identify its sister group with more certainty.

Thaxterogaster revisited: A phylogenetic and taxonomic overview of sequestrate Cortinarius from Patagonia.

In the Patagonian region, Cortinarius is the most diverse and abundant genus of ectomycorrhizal fungi with at least 250 species. Sequestrate forms were until recently documented within the genus Thaxterogaster, a genus now known to be polyphyletic, and many were consequently transferred to Cortinarius. Original descriptions were mostly available in German and Spanish and interpretations of morphological structures outdated. Despite recent advances in Cortinarius systematics, the current classification, diversity, and ecology of sequestrate "cortinarioid" fungi in Patagonia remain unclear. The objective of this study was to provide an update on sequestrate Cortinarius of southern South America. We documented each species with morphological descriptions, photographs, basidiospore scanning electron microscopy (SEM) images, and molecular characterization using nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and nuc 28S rDNA (28S) sequence data. Original descriptions of taxa were also translated to English and revised based on fresh collections. We documented 24 species from Patagonia based on molecular data and conducted morphological and phylogenetic analysis for 18 previously described species based on type and reference specimens. In addition, we formally described two new species. Four additional taxa were provisionally determined as new but require further study. New ITS sequence data were produced from eight type specimens. We also provide a new name, Cortinarius gloiodes, nom. nov., for the taxon previously described as Thaxterogaster gliocyclus. In addition to the species treated in detail, we provided additional reference information and discussion on six described species that remained incompletely known or for which no recent collections were found. Of the 24 taxa documented from Patagonia, 15 species were assigned to 12 current sections in the genus Cortinarius. Analysis of spore ultrastructure showed that sequestrate forms of Patagonian Cortinarius lack a true perisporium.

Dissolvable intranasal haemostatic agents for acute epistaxis: A systematic review and meta-analysis.

INTRODUCTION: Nasal packing is the mainstay of epistaxis management; however, packs cause patient discomfort and can lead to hospital admission. Absorbable haemostats provide clotting factors or act as a substrate to stimulate clotting and represent a potential treatment alternative. A systematic review was performed to evaluate the efficacy of topical haemostats in the management of epistaxis. METHODS: A systematic literature search of 7 databases was performed. Only eligible randomised controlled trials (RCTs) and observational studies were included. The primary outcome was short-term haemostatic success (<7 days). Secondary outcomes included long-term haemostatic control (no rebleeding 7-30 days), patient discomfort and adverse effects. Meta-analysis was performed where possible. RESULTS: Of 2249 records identified, 12 were included in the qualitative synthesis and 4 RCTs were included in meta-analysis. The following haemostats were reported: gelatin-thrombin matrix (n = 8), aerosolised/gel tranexamic acid (n = 1), cellulose agents (n = 2) and fibrin sealants (n = 1). Studies involving tranexamic acid on removable delivery devices (eg, pledgets) were excluded. There was heterogeneity in outcome measures and inclusion criteria (coagulopathies/anticoagulants were excluded in 3 RCTs and 2 observational studies). The short-term haemostatic success varied between studies (13.9% to 100%). No significant post-procedural complications were reported. The meta-analysis favoured absorbable haemostatic agent versus packing (risk ratio 1.20; 95% confidence interval 1.05 to 1.37; P = .007). The risk of bias across all studies was moderate to high. CONCLUSIONS: The evidence suggests haemostatic agents are effective at managing acute epistaxis when compared with nasal packing. More data are required before recommendations can be made regarding management in patients on anticoagulants.

Paediatric tonsillectomy in England: A cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008-2019).

OBJECTIVES: To assess the safety of paediatric tonsillectomy procedures conducted in NHS hospitals in England between 2008 and 2019. DESIGN: Retrospective observational cohort study using Hospital Episode Statistics (HES) data. SETTING: Acute NHS trusts in England conducting paediatric tonsillectomy procedures. PARTICIPANTS: Children (≤16 years old) undergoing bilateral tonsillectomy. MAIN OUTCOME MEASURES: Number of tonsillectomies performed per year by procedural method. In-hospital complications including return to theatre for arrest of haemorrhage. Readmission within 28 days, including those for pain, haemorrhage and surgical arrest of haemorrhage. Long-term outcomes: all-cause mortality, revision tonsillectomy. RESULTS: A total of 318 453 paediatric tonsillectomies were performed from 2008 to 2019:278,772 dissection (87.5%) and 39 681 coblation (12.5%). The proportion of tonsillectomy performed using coblation increased from 7% in 2008/9 to 27% in 2018/9. Five patients died in hospital (including 4 due to respiratory complications). In-hospital complications occurred in 4202 children (1.3%), with the most frequent being haemorrhage. Within 28 days of tonsillectomy, 28 170 patients (8.8%) were readmitted and 7 deaths occurred. Readmission rates for haemorrhage and pain have increased since 2008. The proportion of children undergoing revision tonsillectomy procedures within 5 years following coblation tonsillectomy (1.4%) was approximately double that of dissection (0.6%). CONCLUSIONS: Clinical practice of paediatric tonsillectomy has changed in England over the past 11 years. The overall mortality rate associated with the procedure is 0.0037%. Differences in outcomes have been identified for different procedural methods. However, routine administrative data are limited in differentiating procedural detail (eg we are unable to differentiate intra or extra-capsular techniques from current clinical coding of tonsillectomy procedures). Therefore, prospective national data collection or more granular clinical coding is essential to capture relative outcomes of the different tonsillectomy methods and techniques being used in the NHS.

The Ambrosia Beetle Sueus niisimai (Scolytinae: Hyorrhynchini) is Associated with the Canker Disease Fungus Diatrypella japonica (Xylariales).

Ambrosia beetles in the subtribe Hyorrhynchini are one example of an entire ambrosia beetle lineage whose fungi have never been studied. Here, we identify one dominant fungus associated with a widespread Asian hyorrhynchine beetle Sueus niisimai. This fungus was consistently isolated from beetle galleries from multiple collections. Phylogenetic analyses of combined ITS rDNA and ß-tubulin sequences identified the primary fungal symbiont as Diatrypella japonica Higuchi, Nikaido & Hattori (Diatrypaceae, Xylariales, Sordariomycetes), which was recently described as a pathogen of sycamore (Platanus spp.) in Japan. To assess the invasion potential of this beetle-fungus interaction into the U.S., we have investigated the pathogenicity of two D. japonica strains on four species of healthy landscape trees native to the southeastern United States. Only Shumard oak (Quercus shumardii) responded with lesions significantly greater than the control inoculations, but there was no observable dieback or tree mortality. Although disease symptoms were not as prominent as in previous studies of the same fungus in Japan, routine reisolation from the inoculation point suggests that this species is capable of colonizing healthy sapwood of several tree species. Our study shows that the geographical area of its distribution is broader in Asia and potentially includes many hosts of its polyphagous vector. We conclude that the Sueus-Diatrypella symbiosis has high invasion potential but low damage potential, at least on young trees during the growing season.

Engineered transient and stable overexpression of translation factors eIF3i and eIF3c in CHOK1 and HEK293 cells gives enhanced cell growth associated with increased c-Myc expression and increased recombinant protein synthesis.

There is a desire to engineer mammalian host cell lines to improve cell growth/biomass accumulation and recombinant biopharmaceutical protein production in industrially relevant cell lines such as the CHOK1 and HEK293 cell lines. The over-expression of individual subunits of the eukaryotic translation factor eIF3 in mammalian cells has previously been shown to result in oncogenic properties being imparted on cells, including increased cell proliferation and growth and enhanced global protein synthesis rates. Here we report on the engineering of CHOK1 and HEK cells to over-express the eIF3i and eIF3c subunits of the eIF3 complex and the resultant impact on cell growth and a reporter of exogenous recombinant protein production. Transient over-expression of eIF3i in HEK293 and CHOK1 cells resulted in a modest increase in total eIF3i amounts (maximum 40% increase above control) and an approximate 10% increase in global protein synthesis rates in CHOK1 cells. Stable over-expression of eIF3i in CHOK1 cells was not achievable, most likely due to the already high levels of eIF3i in CHO cells compared to HEK293 cells, but was achieved in HEK293 cells. HEK293 cells engineered to over-express eIF3i had faster growth that was associated with increased c-Myc expression, achieved higher cell biomass and gave enhanced yields of a reporter of recombinant protein production. Whilst CHOK1 cells could not be engineered to over-express eIF3i directly, they could be engineered to over-express eIF3c, which resulted in a subsequent increase in eIF3i amounts and c-Myc expression. The CHOK1 eIF3c engineered cells grew to higher cell numbers and had enhanced cap- and IRES-dependent recombinant protein synthesis. Collectively these data show that engineering of subunits of the eIF3 complex can enhance cell growth and recombinant protein synthesis in mammalian cells in a cell specific manner that has implications for the engineering or selection of fast growing or high producing cells for production of recombinant proteins.

Longistriata flava (Boletaceae, Basidiomycota) - a new monotypic sequestrate genus and species from Brazilian Atlantic Forest.

A new monotypic sequestrate genus, Longistriata is described based on collections from the Neotropical forest of Atlantic forest in Paraíba, Northeast Brazil - an area known for its high degree of endemism. The striking features of this new fungus are the hypogeous habit, the vivid yellow peridium in mature basidiomes, broadly ellipsoid basidiospores with a distinct wall that is ornamented with longitudinal striations and lageniform cystidia with rounded apices. Phylogenetic analysis, based on LSU and tef-1α regions, showed that the type species, Longistriata flava, is phylogenetically sister to the monotypic sequestrate African genus Mackintoshia in Boletaceae. Together these two species formed the earliest diverging lineage in the subfamily Zangioideae. Longistriata flava is found in nutrient-poor white sand habitats where plants in the genera Coccoloba (Polygonaceae) and Guapira (Nyctaginaceae) are the only potential ectomycorrhizal host symbionts.