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ASO Author Reflections: Modern-Day Implementation of Robotic Esophagogastric Cancer Surgery.
No full textSafety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.
No full textBACKGROUND
Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT).
METHODS
COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.
FINDINGS
Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.
INTERPRETATION
All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.
FUNDING
UK Vaccine Taskforce and National Institute for Health Research
Impact of COVID-19 on global burn care.
No full textBACKGROUND
Worldwide, different strategies have been chosen to face the COVID-19-patient surge, often affecting access to health care for other patients. This observational study aimed to investigate whether the standard of burn care changed globally during the pandemic, and whether country´s income, geographical location, COVID-19-transmission pattern, and levels of specialization of the burn units affected reallocation of resources and access to burn care.
METHODS
The Burn Care Survey is a questionnaire developed to collect information on the capacity to provide burn care by burn units around the world, before and during the pandemic. The survey was distributed between September and October 2020. McNemar`s test analyzed differences between services provided before and during the pandemic, χ2 or Fisher's exact test differences between groups. Multivariable logistic regression analyzed the independent effect of different factors on keeping the burn units open during the pandemic.
RESULTS
The survey was completed by 234 burn units in 43 countries. During the pandemic, presence of burn surgeons did not change (p = 0.06), while that of anesthetists and dedicated nursing staff was reduced (<0.01), and so did the capacity to manage patients in all age groups (p = 0.04). Use of telemedicine was implemented (p < 0.01), collaboration between burn centers was not. Burn units in LMICs and LICs were more likely to be closed, after adjustment for other factors.
CONCLUSIONS
During the pandemic, most burn units were open, although availability of standard resources diminished worldwide. The use of telemedicine increased, suggesting the implementation of new strategies to manage burns. Low income was independently associated with reduced access to burn care
Robotic Techniques in Esophagogastric Cancer Surgery: An Assessment of Short- and Long-Term Clinical Outcomes.
No full textBACKGROUND
Robotic esophagogastric cancer surgery is gaining widespread adoption. This population-based cohort study aimed to compare rates of textbook outcomes (TOs) and survival from robotic minimally invasive techniques for esophagogastric cancer.
METHODS
Data from the United States National Cancer Database (NCDB) (2010-2017) were used to identify patients with non-metastatic esophageal or gastric cancer receiving open surgery (to the esophagus, n = 11,442; stomach, n = 22,183), laparoscopic surgery (to the esophagus [LAMIE], n = 4827; stomach [LAMIG], n = 6359), or robotic surgery (to the esophagus [RAMIE], n = 1657; stomach [RAMIG], n = 1718). The study defined TOs as 15 or more lymph nodes examined, margin-negative resections, hospital stay less than 21 days, no 30-day readmissions, and no 90-day mortalities. Multivariable logistic regression and Cox analyses were used to account for treatment selection bias.
RESULTS
Patients receiving robotic surgery were more commonly treated in high-volume academic centers with advanced clinical T and N stage disease. From 2010 to 2017, TO rates increased for esophageal and gastric cancer treated via all surgical techniques. Compared with open surgery, significantly higher TO rates were associated with RAMIE (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.27-1.58) and RAMIG (OR 1.30; 95% CI 1.17-1.45). For esophagectomy, long-term survival was associated with both TO (hazard ratio [HR 0.64, 95% CI 0.60-0.67) and RAMIE (HR 0.92; 95% CI 0.84-1.00). For gastrectomy, long-term survival was associated with TO (HR 0.58; 95% CI 0.56-0.60) and both LAMIG (HR 0.89; 95% CI 0.85-0.94) and RAMIG (HR 0.88; 95% CI 0.81-0.96). Subset analysis in high-volume centers confirmed similar findings.
CONCLUSION
Despite potentially adverse learning curve effects and more advanced tumor stages captured during the study period, both RAMIE and RAMIG performed in mostly high-volume centers were associated with improved TO and long-term survival. Therefore, consideration for wider adoption but a well-designed phase 3 randomized controlled trial (RCT) is required for a full evaluation of the benefits conferred by robotic techniques for esophageal and gastric cancers
Survival benefit with adjuvant radiotherapy after resection of distal cholangiocarcinoma: A propensity-matched National Cancer Database analysis.
No full textBACKGROUND
No convincing evidence for the benefit of adjuvant radiotherapy (RT) following resection of distal cholangiocarcinoma (dCCA) exists, especially for lower-risk (margin- or node-negative) disease. Hence, the association of adjuvant RT on survival after surgical resection of dCCA was compared with no adjuvant RT (noRT).
METHODS
Using National Cancer Database data from 2004 to 2016, patients undergoing pancreatoduodenectomy for nonmetastatic dCCA were identified. Patients with neoadjuvant RT and chemotherapy and survival <6 months were excluded. Propensity score matching was used to account for treatment-selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of adjuvant RT with survival.
RESULTS
Of 2162 (34%) adjuvant RT and 4155 (66%) noRT patients, 1509 adjuvant RT and 1509 noRT patients remained in the cohort after matching. The rates of node-negative disease (N0), node-positive disease (N+), and unknown node status (Nx) were 39%, 51%, and 10%, respectively. After matching, adjuvant RT was associated with improved survival (median, 29.3 vs 26.8 months; P < .001), which remained after multivariable adjustment (HR, 0.86; 95% CI, 0.80-0.93; P < .001). Multivariable interaction analyses showed this benefit was seen irrespective of nodal status (N0: HR, 0.77; 95% CI, 0.66-0.89; P < .001; N+: HR, 0.79; 95% CI, 0.71-0.89; P < .001) and margin status (R0: HR, 0.58; 95% CI, 0.50-0.67; P < .001; R1: HR, 0.87; 95% CI, 0.78-0.96; P = .007). Stratified analyses by nodal and margin status demonstrated consistent results.
CONCLUSIONS
Adjuvant RT after dCCA resection was associated with a survival benefit in patients, even in patients with margin- or node-negative resections. Adjuvant RT should be considered routinely irrespective of margin and nodal status after resection for dCCA.
LAY SUMMARY
Adjuvant radiotherapy after resection of distal cholangiocarcinoma was associated with a survival benefit in patients, even in patients with margin-negative or node-negative resections. Adjuvant radiotherapy should be considered routinely irrespective of margin and nodal status after resection of distal cholangiocarcinoma
Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.
No full textINTRODUCTION
In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing.
METHODS
COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases.
FINDINGS
Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities.
CONCLUSION
Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment
Collaborative Overview of coronaVIrus impact on ORTHopaedic training in the UK (COVI - ORTH UK).
No full textINTRODUCTION
COVID-19 was declared a pandemic by the World Health Organization on the 11th of March 2020 with the NHS deferring all non-urgent activity from the 15th of April 2020. The aim of our study was to assess the impact of COVID-19 on Trauma and Orthopaedic trainees nationally.
METHODS
Trauma and Orthopaedic (T&O) specialty trainees nationally were asked to complete an electronic survey specifically on the impact of COVID-19 on their training. This UK based survey was conducted between May 2020 and July 2020.
RESULTS
A total of 185 out of 975 (19%) T&O specialty trainees completed the survey. Redeployment was experienced by 25% of trainees. 84% of respondents had experienced a fall in total operating numbers in comparison with the same time period in 2019. 89% experienced a fall in elective operating and 63% experienced a fall in trauma operating. The pandemic has also had an effect on the delivery of teaching, with face to face teaching being replaced by webinar-based teaching. 63% of training programmes delivered regular weekly teaching, whilst 19% provided infrequent sessions and 11% provided no teaching.
CONCLUSION
This study has objectively demonstrated the significant impact of the COVID-19 pandemic on all aspects of T&O training
ESPRAS Survey on Breast Reconstruction in Europe.
No full textBACKGROUND
The European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) previously identified the need for harmonisation of breast reconstruction standards in Europe, in order to strengthen the role of plastic surgeons. This study aims to survey the status, current trends and potential regional differences in the practice of breast reconstruction in Europe, with emphasis on equity and access.
MATERIALS AND METHODS
A largescale web-based questionnaire was sent to consultant plastic and reconstructive surgeons, who are experienced in breast reconstruction and with understanding of the national situation in their country. Suitable participants were identified via the Executive Committee (ExCo) of ESPRAS and national delegates of ESPRAS. The results were evaluated and related to evidence-based literature.
RESULTS
A total of 33 participants from 29 European countries participated in this study. Overall, the incidence of breast reconstruction was reported to be relatively low across Europe, comparable to other large geographic regions, such as North America. Equity of provision and access to breast reconstruction was distributed evenly within Europe, with geographic regions potentially affecting the type of reconstruction offered. Standard practices with regard to radiotherapy differed between countries and a clear demand for European guidelines on breast reconstruction was reported.
CONCLUSION
This study identified distinct lack of consistency in international practice patterns across European countries and a strong demand for consistent European guidance. Large-scale and multi-centre European clinical trials are required to further elucidate the presented areas of interest and to define European standard operating procedures