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Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss.
No full textPersistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: three month analyses of the COV-BOOST trial.
No full textOBJECTIVES
To evaluate the persistence of immunogenicity three months after third dose boosters.
METHODS
COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.
RESULTS
Among the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAd, schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10085) following ChAd/ChAd/BNT). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.
CONCLUSIONS
84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentration at D84 following BNT/BNT initial doses were higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses
Assessing spinal movement during four extrication methods: a biomechanical study using healthy volunteers.
No full textBACKGROUND
Motor vehicle collisions are a common cause of death and serious injury. Many casualties will remain in their vehicle following a collision. Trapped patients have more injuries and are more likely to die than their untrapped counterparts. Current extrication methods are time consuming and have a focus on movement minimisation and mitigation. The optimal extrication strategy and the effect this extrication method has on spinal movement is unknown. The aim of this study was to evaluate the movement at the cervical and lumbar spine for four commonly utilised extrication techniques.
METHODS
Biomechanical data was collected using inertial Measurement Units on 6 healthy volunteers. The extrication types examined were: roof removal, b-post rip, rapid removal and self-extrication. Measurements were recorded at the cervical and lumbar spine, and in the anteroposterior (AP) and lateral (LAT) planes. Total movement (travel), maximal movement, mean, standard deviation and confidence intervals are reported for each extrication type.
RESULTS
Data from a total of 230 extrications were collected for analysis. The smallest maximal and total movement (travel) were seen when the volunteer self-extricated (AP max = 2.6 mm, travel 4.9 mm). The largest maximal movement and travel were seen in rapid extrication extricated (AP max = 6.21 mm, travel 20.51 mm). The differences between self-extrication and all other methods were significant (p < 0.001), small non-significant differences existed between roof removal, b-post rip and rapid removal. Self-extrication was significantly quicker than the other extrication methods (mean 6.4 s).
CONCLUSIONS
In healthy volunteers, self-extrication is associated with the smallest spinal movement and the fastest time to complete extrication. Rapid, B-post rip and roof off extrication types are all associated with similar movements and time to extrication in prepared vehicles
Comparing Hearing Outcomes in Irradiated and Conservatively Managed Vestibular Schwannoma.
No full textOBJECTIVE
Compare hearing outcome for vestibular schwannoma patients following stereotactic radiosurgery (SRS) or conservative management.
STUDY DESIGN
Retrospective review.
SETTING
University Hospital.
PATIENTS
Patients with small- or medium-sized sporadic vestibular schwannoma (intracanalicular or with CPA component <2 cm) who were managed conservatively or underwent SRS with available clinical, radiological, and audiometric data from the time of presentation (or just before radiotherapy for the SRS group) and most recent follow-up; with the two sets of data to be compared being at least 3 years apart (minimum follow-up period).
INTERVENTIONS
SRS or observation.
MAIN OUTCOME MEASURE
Pure-tone averages, speech discrimination scores, and corresponding hearing classifications.
RESULTS
Two hundred forty-seven patients met our inclusion criteria; 140 were managed conservatively with a mean follow-up period of 5.9 ± 1.6 years and 107 underwent SRS with a mean follow-up period of 7.1 ± 1.9 years. There was significant deterioration of hearing measures for both groups; with the SRS group displaying consistently worse measures. SRS patients showed worse mean pure-tone averages and speech discrimination scores decline rates by 2.72 dB/yr and 2.98 %/yr, respectively, when compared with conservatively managed patients. Stratifying patients according to Tokyo's hearing classification revealed that 68.75% of conservatively managed patients who had baseline serviceable hearing preserved their hearing throughout the studied period compared with only 15.38% of the SRS patients.
CONCLUSION
Based on our data we conclude that patients with small- and medium-sized tumors will have a better hearing outcome if managed via an initial conservative approach with radiotherapy reserved for those demonstrating disease progression
Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.
No full textSARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 post-mortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID post-mortem controls. SARS-CoV-2 anti-NP staining in the post-mortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained post-mortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE-2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms to the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. This article is protected by copyright. All rights reserved
Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial.
No full textBACKGROUND
Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer-BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax).
METHODS
Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8-12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311.
FINDINGS
Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation.
INTERPRETATION
Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification.
FUNDING
UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax
Definitions and treatment of oligometastatic oesophagogastric cancer according to multidisciplinary tumour boards in Europe.
No full textBACKGROUND
Consensus about the definition and treatment of oligometastatic oesophagogastric cancer is lacking.
OBJECTIVE
To assess the definition and treatment of oligometastatic oesophagogastric cancer across multidisciplinary tumour boards (MDTs) in Europe.
MATERIAL AND METHODS
European expert centers (n = 49) were requested to discuss 15 real-life cases in their MDT with at least a medical, surgical, and radiation oncologist present. The cases varied in terms of location and number of metastases, histology, timing of detection (i.e. synchronous versus metachronous), primary tumour treatment status, and response to systemic therapy. The primary outcome was the agreement in the definition of oligometastatic disease at diagnosis and after systemic therapy. The secondary outcome was the agreement in treatment strategies. Treatment strategies for oligometastatic disease were categorised into upfront local treatment (i.e. metastasectomy or stereotactic radiotherapy), systemic therapy followed by restaging to consider local treatment or systemic therapy alone. The agreement across MDTs was scored to be either absent/poor (<50%), fair (50%-75%), or consensus (≥75%).
RESULTS
A total of 47 MDTs across 16 countries fully discussed the cases (96%). Oligometastatic disease was considered in patients with 1-2 metastases in either the liver, lung, retroperitoneal lymph nodes, adrenal gland, soft tissue or bone (consensus). At follow-up, oligometastatic disease was considered after a median of 18 weeks of systemic therapy when no progression or progression in size only of the oligometastatic lesion(s) was seen (consensus). If at restaging after a median of 18 weeks of systemic therapy the number of lesions progressed, this was not considered as oligometastatic disease (fair agreement). There was no consensus on treatment strategies for oligometastatic disease.
CONCLUSION
A broad consensus on definitions of oligometastatic oesophagogastric cancer was found among MDTs of oesophagogastric cancer expert centres in Europe. However, high practice variability in treatment strategies exists
Management of fracture-related infection in low resource settings: how applicable are the current consensus guidelines?
No full textThe global burden of fracture-related infection (FRI) is likely to be found in countries with limited healthcare resources and strategies are needed to ensure the best available practice is context appropriate. This study has two main aims: (i) to assess the applicability of recently published expert guidance from the FRI consensus groups on the diagnosis and management of FRI to low- and middle-income countries (LMICs); (ii) to summarise the available evidence on FRI, with consideration for strategies applicable to low resource settings. Data related to the International Consensus Meeting Orthopaedic Trauma Work Group and the International Fracture Related Infection Consensus Group FRI guidelines were collected including panel membership, country of origin, language of publication, open access status and impact factor of the journal of publication. The recommendations and guidelines were then summarised with specific consideration for relevance and applicability to LMICs. Barriers to implementation were explored within a group of LMIC residents and experienced workers. The authorship, evidence base and reach of the FRI consensus guidelines lack representation from low resource settings. The majority of authors (78.5-100%) are based in high-income countries and there are no low-income country collaborators listed in any of the papers. All papers are in English. The FRI consensus guidelines give a clear set of principles for the optimum management of FRI. Many of these - including the approach to diagnosis, multidisciplinary team working and some elements of surgical management - are achievable in low resource settings. Current evidence suggests that it is important that a core set of principles is prioritised but robust evidence for this is lacking. There are major organisational and infrastructure obstacles in LMICs that will make any standardisation of FRI diagnosis or management challenging. The detail of how FRI consensus principles should be applied in low resource settings requires further work. The important work presented in the current FRI consensus guidelines is relevant to low resource settings. However, leadership, collaboration, creativity and innovation will be needed to implement these strategies for communities who need it the most
Surgical and Functional Outcomes of Artery Only Versus Artery and Vein Clamping in Patients Undergoing Partial Nephrectomy: A Systematic Review and Meta-Analysis.
No full textClamping of renal vessels during partial nephrectomy is usually performed to improve the visualization of tumor margins. However, clamping of renal vessels has been associated with detrimental effects on renal function after surgery. This study aimed to compare artery only versus artery and vein clamping as regards the surgical and functional outcomes in patients undergoing partial nephrectomy. The literature was searched for English published studies from January 1, 2000 to August 7, 2021. The search included MEDLINE/ PubMed, Cochrane Library, Scopus, Web of Science, Google Scholar, and ProQuest, using the terms {"par- tial nephrectomy"} OR {"nephron-sparing surgery"} AND {"renal artery and vein clamping} AND {"renal artery only clamping}. Nine studies were included. Meta-analysis showed the artery only clamping grouphad a significantly less percentage of change in glomerular filtration rate at last follow-up (standardizedmean difference: -0.42 [95% CI: -0.70, -0.13], P = .004) as well as a rate of postoperative complications(odds ratio: 0.64 [95% CI: 0.41, 0.98], P = .04). However, no significant difference was observed regarding the development of chronic kidney disease. There was no significant difference regarding the warm ischemiatime, blood loss, or positive surgical margin. Artery only clamping has a comparable safety to artery and vein clamping and may produce a renoprotective effect. Due to limitations of the included studies, the conduction of large-size randomized clinical trials with a long duration of follow-up is required before recommending the replacement of artery and vein clamping with artery only clamping during partial nephrectomy