bluuebunny/crossref_metadata_2025 huggingface dataset:
SAMPDI-3D: predicting the effects of protein and DNA mutations on protein–DNA interactions
Authors: Li Gen , Panday Shailesh Kumar , Peng Yunhui , Alexov Emil
Published: July 2021

Motivation

Mutations that alter protein–DNA interactions may be pathogenic and cause diseases. Therefore, it is extremely important to quantify the effect of mutations on protein–DNA binding free energy to reveal the molecular origin of diseases and to assist the development of treatments. Although several methods that predict the change of protein–DNA binding affinity upon mutations in the binding protein were developed, the effect of DNA mutations was not considered yet.

Results

Here, we report a new version of SAMPDI, the SAMPDI-3D, which is a gradient boosting decision tree machine learning method to predict the change of the protein–DNA binding free energy caused by mutations in both the binding protein and the bases of the corresponding DNA. The method is shown to achieve Pearson correlation coefficient of 0.76 and 0.80 in a benchmarking test against experimentally determined change of the binding free energy caused by mutations in the binding protein or DNA, respectively. Furthermore, three datasets collected from literature were used to do blind benchmark for SAMPDI-3D and it is shown that it outperforms all existing state-of-the-art methods. The method is very fast allowing for genome-scale investigations.

Availabilityand implementation

It is available as a web server and a stand-code at http://compbio.clemson.edu/SAMPDI-3D/.

Supplementary information

Supplementary data are available at Bioinformatics online.
O2 Mortality following elective and emergency colorectal surgery in patients with cirrhosis: a population-based cohort study
Authors: Adiamah A , Crooks C J , Hammond J S , Jepsen P , West J , Humes D J
Published: July 2021

Introduction

This population based cohort study, aimed to quantify the risk of mortality following colectomy in patients with cirrhosis by urgency of surgery and stage of cirrhosis.

Method

Linked primary and secondary-care electronic healthcare data from England was used to identify all patients undergoing colectomy from January 2001 to December 2017. Patients were classified into three cohorts, non-cirrhotics, compensated cirrhotics and decompensated cirrhosis and followed up for 90-days from the date of surgery. Cox proportional hazards models were used to estimate the hazard ratio (HR) of postoperative mortality.

Result

A total of 36380 eligible patients were included. Of these, 248(0.7%) had liver cirrhosis and 70% had compensated disease. The proportion undergoing a colectomy who had a diagnosis of cirrhosis increased from 0.40% in 2001 to 1.07% in 2017 (χ2(16, N = 36380)=50.53, P < 0.0001).

Following elective colectomy, 90-day case fatality was 4% in non-cirrhotics , 7% in compensated cirrhotics and 10% in decompensated cirrhotics. Following emergency colectomy 90-day case fatality was higher, it was 16% in non-cirrhotics, 35% in compensated cirrhotics and 41% in decompensated cirrhotics. This corresponded to an adjusted 2-fold (HR 2.57(95% CI 1.75–3.76)) and 3-fold (3.43(95% CI 2.02–5.83)) increased mortality rate in compensated and decompensated cirrhotics respectively compared to non-cirrhotics following emergency colectomy.

Conclusion

Over the study period, the proportion of patients undergoing colectomy who had liver cirrhosis increased to 1 in every 100 colectomies. The 90-day case fatality rates were high in all patients with cirrhosis in both emergency and elective settings but the greatest mortality risk was seen in those with decompensation following emergency surgery.

Take-home Message

1 in 100 colectomy procedures are in patients with cirrhosis. These cirrhotic patients have a very high risk of postoperative mortality, especially, emergency colectomy in patients with decompensated cirrhosis.
O3 Ex vivo normothermic machine perfusion facilitates gymnotic delivery of RNA interference therapeutics in donor kidneys
Authors: Thompson E R , Sewpaul A , Figuereido R , Bates L , Ferdinand J R , Connelly C M , Hosgood S A , Nicholson M L , Clatworthy M R , Ali S , Wilson C H , Sheerin N S
Published: July 2021

Introduction

Normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for delivery of novel therapeutics to optimize organ quality. This includes RNA interference (RNAi) therapeutics e.g. antisense oligonucleotides (ASO) that block detrimental microRNAs. The intracellular kinetics of RNAi therapeutics are crucial for their pharmacological effect, however, it remains poorly understood. NMP provides an ideal platform to investigate this further.

Method

During NMP, human kidneys (n = 12) were treated for 6 hours with a fluorescently-labelled ASO designed to block microRNA-24-3p activity. Biopsies were taken at 0, 2, 4, and 6 hours. Kidney sections were stained with antibodies against early endosomes (Rab5), late endosomes (Rab7), RNA-induced silencing complexes (GW182) and lysosomes (LAMP2). Confocal microscopy images were obtained and co-localisation quantified using Hugyens™ software following batch deconvolution. The global transcriptomic impact of ASO therapy was also assessed using RNA sequencing.

Result

Following 2 hours of NMP, ASO was primarily found in tubular epithelial cells. Co-localisation studies revealed ASO uptake via endocytosis and endosomal sorting occurring during NMP. This was followed by cytoplasmic escape and co-localisation of ASO with GW182 proteins. This pattern of co-localisation was not seen in scrambled sequence or cold perfusion controls. RNAseq analysis revealed a decrease in inflammatory pathways and upregulation of microRNA-24-3p targets.

Discussion

This is the first study to demonstrate NMP facilitates gymnotic ASO delivery directly into the RISC, whereby, it blocks microRNA-mediated mRNA silencing and increases bioavailability of protective targets. This study highlights the capacity of NMP to re-programme gene expression in donor kidneys using RNAi therapeutics.

Take-home Message

Ex vivo normothermic machine perfusion of donor kidneys provides a unique window of opportunity prior to transplantation when we can deliver therapies to improve the quality of the organ. Novel genetic therapies designed to protect kidneys against ischemia reperfusion injury could potentially increase organ utilisation and improve post-transplant outcomes for the many patients on the kidney transplant waiting list.
O10 Myocardial tolerance to exsanguination and retrieval using whole blood-selective aortic arch perfusion
Authors: Madurska M J , Elansary N N , Pate N , Edwards J , Richmond M J , Scalea T M , Rasmussen T E , Morrison J J
Published: July 2021

Introduction

Exsanguination cardiac arrest is the leading preventable cause of death in trauma. Treatment modalities are limited, and prognosis remains dismal. Selective aortic arch perfusion (SAAP) is an emerging endovascular resuscitation technique consisting of aortic occlusion and perfusion of coronary and cerebral circulation with oxygenated resuscitation fluid. Translational research has demonstrated promising outcomes; however, little is known about the duration of cardiac arrest beyond which the myocardium cannot be resuscitated. The aims of this study are to assess the myocardial tolerance to exsanguination cardiac arrest before successful return of spontaneous circulation (ROSC) following resuscitation with SAAP, and 1-hour survival.

Method

23 male adult swine were anaesthetised and instrumented. Controlled hemorrhage was performed until cardiac arrest defined by MAP <20 mmHg. Animals were randomized into 3 groups: 5, 10 and 15 minutes of cardiac arrest before resuscitation with SAAP. Following ROSC animals were observed for 60 minutes.

Result

Baseline characteristics were similar between groups (P > 0.05). ROSC was 100% (8/8) in the 5 min group, 75% (6/8) and 43% (3/7) in 10- and 15-min groups respectively (P = 0.042). 60 min survival was 75%, 50% and 14% in 5-, 10- and 15-min groups respectively (P = 0.015). 1-hour survivors in the 5 min group required less noradrenaline 23.6 (±7.4) compared to other animals 40.9 (±25.8), (P = 0.008).

Conclusion

Selective aortic arch perfusion is an effective resuscitative tool in eliciting ROSC in a swine model of exsanguination cardiac arrest lasting >5 min. Sustainable resuscitability using SAAP declines after 10 min of exsanguination cardiac arrest.

Take-home Message

SAAP is an emerging resuscitation technique with promising outcomes in exsanguination cardiac arrest and may be a segway to Extracorporeal life support. The time limit for resuscitability of the myocardium lies somewhere between 10 and 15 min after the start of exsanguination cardiac arrest.
O21 Is hypoalbuminaemia associated with amputation-free survival in chronic limb-threatening ischaemia? A retrospective cohort study
Authors: Nickinson A T O , Black I , Houghton J S M , Sayers R D
Published: July 2021

Introduction

Serum albumin is a recognised marker of nutritional status. Whilst associated with post-operative outcomes, the relationship with amputation-related outcomes in chronic limb-threatening ischaemia (CLTI) remains unclear. It is also uncertain whether any relationship may be confounded by systematic inflammation. We aimed to investigate whether hypoalbuminaemia is associated with amputation-related outcomes and evaluate its relationship with other inflammatory markers.

Method

A retrospective study of patients managed for CLTI at a vascular centre between 01/01/2013–31/12/2015 was undertaken. Patients were identified from local coding databases. Patient demographics and comorbidities, results of admission bloods and procedural data were recorded from electronic records. Hypoalbuminaemia was defined as albumin concentration <35 g/L. One-year amputation-free survival (AFS) was the primary outcome. Cox’s proportional hazard models were calculated to compare the risk of amputation/death. Linear regression was performed to investigate the relationship between albumin and other inflammatory markers.

Result

374 patients were included (mean albumin concentration = 38.8g/L [SD = 5.2]), with 72 patients being hypoalbuminaemic. No differences were observed in sex (P=0.678), age (P=0.207), history of tissue loss (P=0.057), or cardiovascular comorbidities between groups, however a greater proportion of patients with hypoalbuminaemia had COPD (P=0.002). Patients with hypoalbuminaemia had a significantly higher combined risk of 1-year amputation/death compared to those with normal albumin concentration (HR 1.94, 95% CI 1.29–2.91). White cell count and CRP concentration were significant predictors of albumin concentration (r2=0.113, P<0.001).

Conclusion

Hypoalbuminaemia is an important prognostic biomarker of AFS in CLTI, however this association may relate to a complex relationship between nutritional status and inflammation.

Take-home Message

Albumin is more than just a marker of nutritional status in patients with chronic limb-threatening ischaemia.
O22 Risk of death following pulmonary complications of surgery with and without SARS-CoV-2 infection: a comparative analysis of pre-pandemic and pandemic cohort studies
Authors:   STARSurg Collaborative & COVIDSurg Collaborative
Published: July 2021

Introduction

No comparison has been made between the risk of death following pulmonary complications in patients with and without SARS-CoV-2 infection. This study aimed to determine the incidence and impact of pulmonary complications before and during the SARS-CoV-2 pandemic.

Method

A patient-level comparative analysis of two international prospective cohort studies; conducted pre-pandemic (22 January to 19 October 2019) and during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines were included in analysis. The primary outcome measure was the mortality within 30 days of surgery.

Result

This study included 7402 patients from 50 countries; 3031 (40.9%) were operated pre-pandemic and 4371 (59.1%) during the pandemic. 5.1% (n = 224/4371) of patients during the pandemic developed a postoperative SARS-CoV-2 infection. Despite selection of lower risk cases during the pandemic, the rates of pulmonary complications pre were similar (6.3% vs 6.9%, P = 0.280). However, the risk of death after surgery was higher during the pandemic (2.0% vs 0.7%, P < 0.001). The population attributable fraction of deaths due to pulmonary complications was 37.7% (95% CI: 15.2–64.7%) pre-pandemic and 66.0% (95% CI: 48.6–79.3%) during the pandemic. The increased mortality was largely attributable to SARS-CoV-2 infection; 68.9% (n = 31/45) of deaths patients with pulmonary complications occurred following SARS-CoV-2 infection.

Conclusion

Pulmonary complications are the primary driver of death after elective surgery during the pandemic. Care providers must urgently reconfigure surgical services to protect patients from perioperative SARS-CoV-2 infection.

Take-home Message

Pulmonary complications are the primary driver of death after elective surgery during the pandemic. Care providers must urgently reconfigure surgical services to protect patients from perioperative SARS-CoV-2 infection.
O25 Expression of polymeric immunoglobulin receptor (PIGR) and the effect of PIGR overexpression on breast cancer cells
Authors: Asanprakit W , Lobo D N , Eremin O , Bennett A J
Published: July 2021

Introduction

Polymeric immunoglobulin receptor (PIGR) has a major role in mucosal immunity as a transporter of polymeric immunoglobulin across the epithelial cells. PIGR expression increases in various cancers and relates to patient outcomes. Functional roles of PIGR have been explored in several cancers such as hepatocellular, pancreatic and lung cancer. The aim of this study was to determine the effect of PIGR on cellular behaviours and chemo-sensitivity of MCF7 and MDA-MB468 breast cancer cell lines.

Method

Basal levels of PIGR mRNA and protein expression in MCF7 and MDA-MB468 cells were evaluated by real time quantitative polymerase chain reaction and Western blotting, respectively. MCF7/PIGR and MDA-MB468/PIGR stable cell lines, overexpressing the PIGR gene, were generated using a lentiviral vector with tetracycline dependent induction of expression. Cell viability, cell proliferation and chemo-sensitivity of PIGR transfected cells were evaluated and compared with un-transfected cells to determine the effect of PIGR overexpression on cell phenotype.

Result

The levels of PIGR mRNA and protein expression were significantly higher in MDA-MB468 cells than in MCF7 cells (380-fold, P < 0.0001). However, the differential expression of PIGR in these two cell lines did not lead to significant differences in chemo-sensitivity. Viral overexpression of PIGR was also not found to change any of the parameters measured in either cell line.

Conclusion

PIGR per se does not affect cellular behaviours and chemo-sensitivity of these breast cancer cell lines. It may be a marker which works through other factors rather than being a direct contributor of the favourable outcome in patients.

Take-home Message

PIGR may be a marker of favourable outcome in breast cancer patients which works through other factors rather than being a direct contributor.
O27 The diameter of an anorectal physiology catheter in the anal canal influences the results
Authors: Byrne C M , Kiff E S , Sharma A , Telford K J
Published: July 2021

Introduction

Conventional “catheter-based” anorectal physiology systems may influence anal canal pressures by stretching the sphincters thereby increasing tension. Anal acoustic reflectometry (AAR) is a “catheter-less” technique as the flexible thin catheter does not distort the anal canal. The aim of this study was to explore whether the size of rigid tube in the anal canal had any effect on tension.

Method

Participants with no anorectal dysfunction were included. Baseline resting/squeeze AAR measurements were recorded, then repeated with a 6 mm and 10 mm rigid tube placed along-side the AAR catheter. This process was repeated for anorectal manometry (ARM) and Opening pressure (AAR) and mean resting pressure (MRP) were used to calculate tension (pressure (mmHg) x radius (mm)).

Result

9 participants were included (7 female/2male) with median age 22 years (21–31 years). Tension at rest (no additional tube) for AAR and ARM was 14 and 135 N/m respectively and 33 and 238 N/m during squeeze. Tension increased in a linear fashion, for both resting and squeeze, as the size of additional rigid tube increased. The largest increase in tension from baseline AAR and ARM measurements was recorded with the 10 mm additional tube (1,807% and 102% respectively).

Conclusion

The thin AAR catheter exerted the lowest tension at baseline. A large increase in tension was observed as the size of tube increased and therefore the diameter of catheter used in the assessment of anal physiology will affect the results. ARM measurements carried out by devices of different diameter will not be comparable.

Take-home Message

The diameter of the anorectal physiology catheter in the anal canal influences the results.
O30 Aberrant expression of noggin has a subtype specific association with survival of breast cancer patients
Authors: Liu Ming , Jiang Wen G , Ye Lin
Published: July 2021

Introduction

Noggin is an antagonist of bone morphogenetic proteins (BMP). High Noggin expression contributes formation of osteolytic bone lesions from breast cancer. However, the exact role of noggin in breast cancer is yet to be clarified.

Method

Expression of Noggin was analysed in both RNA sequencing data of breast cancer cohort (n = 1097) from The Cancer Genome Atlas (TCGA) and a gene array database of breast cancer (E-MTAB-6703, n = 2088). Expression of Noggin was analysed using ANOVA and Kaplan-Meier analysis. Correlation between Noggin and angiogenic markers was evaluated using Spearman test. Impact on tumour growth was determined in a murine xenograft model by implant a triple negative breast cancer cell line (MDA-MB-231) with Noggin overexpression.

Result

Down-regulation of Noggin is revealed in both TCGA breast cancer cohort and the E-MTAB-6703. Reduced Noggin presents a correlation with poor relapse free survival. Moreover, patients with shorter overall survival exhibited higher expression of Noggin. Further analysis indicated that Noggin plays differential role in different subtypes of breast cancer. Lower expression of Noggin was seen in Her2 positive breast cancer compared with Luminal and Triple negative breast cancer (0.09(0.05–0.15) vs 0.13(0.06–0.24) vs 0.10(0.04–0.25) P < 0.001). Noggin expression is positively correlated with BMP2, ACVR2A and ACVR1B and also fibroblast growth factor (FGF). Noggin reduced the in vivo tumour growth.

Conclusion

Noggin is reduced in breast cancer. Noggin expression has a subtype specific association with patients' survival in which the Noggin targeted BMP ligands and downstream receptors might be involved. Noggin inhibited in vivo tumour growth of MDA-MB-231 cells.

Take-home Message

Noggin is reduced in breast cancer. Noggin expression has s subtype specific association with patients’ survival in which the Noggin targeted BMP ligands and downstream receptors might be involved.
O36 The impact of the COVID-19 pandemic on undergraduate medical education: a survey of students’ safety and satisfaction during breast surgery clinical placement
Authors: Gasiea Rehab , Gasiea Rayhan , Yip Christina
Published: July 2021

Introduction

COVID-19 is affecting all medical education and training. The University used in the collection of data suspended all clinical placement from mid-March 2020, resuming in-person teaching from September. To enable social distancing, the medical school and Breast Unit introduced: 1. one student per clinician per clinical activity (3-hours), 2. online learning (1-hr) and patient exposure (2 hours) in some clinical activities, 3. remote learning via Teams, and 4. personal protective equipment.

Method

We sent a 24-question survey to 31, 3rd and 4th year, students, who had breast surgery clinical placement between 07/09/20 and 18/12/20. The aim was to assess whether clinical activities could still feasibly be carried out, the effectiveness of COVID-19 protection, and students’ learning satisfaction.

Result

Our survey achieved a 65% response-rate. Over two-thirds of students had at least 3 days’ clinical placement, attending clinics, theatre, mammography, multidisciplinary team meetings and a 3-hr lecture via Teams. 90% of students had face-to-face patient interaction and 70% conducted physical examinations. All students were provided with hand-gel and masks and, at clinics, 35% of students were provided with face-shields. None of the students reported COVID-19 related symptoms during or after placement. 85% of students felt safe during their clinical placement and 95% reported satisfaction with the quality of teaching.

Conclusion

Notwithstanding COVID-19 restrictions, a blend of face-to-face with online clinical teaching can be safely delivered.

Take-home Message

Notwithstanding COVID-19 restrictions, a blend of face-to-face with online clinical teaching can be safely delivered.
O38 Variations in orthopedic trauma presentation during COVID-19 lockdown
Authors: Chaudhry Mansoor N , Ahmad Mahmood , Butt Abeeda
Published: July 2021

Introduction

The first national lockdown was imposed in Ireland from 27th March 2020, to combat the spread of Coronavirus. All non-essential travel, businesses, sporting activities and schools were closed. The elderly were advised to cocoon. The roadmap to easing the restrictions started in May. The lockdown measures resulted in people spending more time indoors, with impact on social and personal wellbeing. This had the potential to increase alcohol consumption, self inflicted injuries and neglect. The purpose of our study is to analyze the variations in orthopedic trauma presentations during the pandemic compared to similar period in 2018 and 2019.

Method

Retrospective data was collected from Orthopedic theatre registry of Our Lady of Lourdes Hospital, Drogheda, Co Louth, Ireland. Patients operated by orthopedic trauma team in three months period (March, April & May) in 2018, 2019 and 2020 were selected for analysis and comparison.

Result

Total number of surgeries performed in March-May 2018, 2019 and 2020 were 551, 505 and 373 showing a significant reduction in 2020 as compared to previous years. Trauma surgeries performed on children in March-May 2018,2019 and 2020 were 132,131 and 90 respectively, showing a similar downward trend. Surgeries were further categorized into Major +, Major, Intermediate and Minor according to their level of complexity. Although there was a significant reduction seen in Major, Intermediate and Minor surgeries, no significant difference was observed in Major + surgeries (73 in March-May 2020 vs. 79 in March-May 2019 and 57 in March-May 2018).

Conclusion

Significant reduction was seen in overall trauma surgeries which is attributable to lockdown measures. The difference in trend between Major + and other categories of surgeries can be explained by the reduction in sporting injuries and injuries in children whereas no significant difference was noted in hip fractures.
O41 Quantifying the burden of survivorship associated with infra-renal abdominal aortic aneurysm repair: a systematic review
Authors: Patel K , Sounderajah V , Normahani P , Acharya A , Ashrafian H , Bicknell C
Published: July 2021

Introduction

Survivorship encompasses the physical, psychological, social, functional and economic experience of living with a chronic condition for both patients and their caregivers. It comprises 9 distinct domains and remains understudied in non-oncological pathologies, including infra-renal abdominal aortic aneurysmal disease (IRAAA). This review aims to quantify the extent to which existing IRAAA literature addresses the burden of survivorship in patients following surgical intervention.

Method

The databases; MEDLINE, EMBASE and PsychINFO, were searched from 1989 through to July 2020. Randomised controlled trials, observational studies and case series studies were included. Eligible studies had to detail outcomes related to survivorship following IRAAA surgery. Due to heterogeneity between studies and outcomes, no meta-analysis was conducted. Study quality was assessed with specific risk of bias tools.

Result

112 studies were included and only 4 of the 9 domains of survivorship have been previously studied—treatment complications, physical functioning, co-morbidities and caregivers. The available evidence is of variable quality; the majority of studies display a moderate to high risk of bias, are of an observational study design, are based within a limited number of countries and consist of an insufficient follow up period.

Conclusion

This review highlights the absence of robust evidence regarding survivorship following IRAAA surgery, regardless of repair modality. Consequently, contemporary treatment guidelines are reliant upon historic quality of life data that is narrow in scope and non-representative of contemporary clinical practice. As such, there is an urgent need to re-evaluate the scope and methodology associated with this research theme moving forwards.

Take-home Message

There is an urgent need to re-evaluate the scope and methodology associated with traditional quality of life centred IRAAA studies moving forwards in order to better empower patient decision making as well as inform treatment guidelines and health policy initiatives.
O44 Gender bias and sexual discrimination in orthopaedics: time for change
Authors: Halim U A , Elbayouk A , Ali A M , Cullen C M , Javed S
Published: July 2021

Introduction

Gender bias and sexual discrimination (GBSD) have been widely recognized across a range of fields and are now part of the wider social consciousness. Such conduct can occur in the medical workplace, with detrimental effects on recipients. The aim of this review was to identify the prevalence and impact of GBSD in orthopaedic surgery, as well as mitigating strategies.

Method

A systematic review was conducted by searching Medline, EMCARE, CINAHL, PsycINFO, and the Cochrane Library Database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Original research papers pertaining to the prevalence and impact of GBSD, or mitigating strategies, within orthopaedics were reviewed.

Result

Of 570 papers, 27 were eligible for inclusion. These were published between 1998 and 2020. 13 papers discussed the prevalence of GBSD, 13 related to the impact of these behaviours, and six discussed mitigating strategies. GBSD was found to be common in the orthopaedic workplace, with all sources showing women to be the subjects. Effects include poor workforce representation, lower salaries, and less career success for women in orthopaedics. Mitigating strategies in the literature are focused on providing female role models, mentors, and educational interventions.

Conclusion

GBSD is common in orthopaedic surgery, with a substantial impact on sufferers. A small number of mitigating strategies have been tested but these are limited in their scope. As such, the orthopaedic community is obliged to participate in more thoughtful and proactive strategies that mitigate against GBSD, by improving female recruitment and retention within the specialty.

Take-home Message

Gender bias and sexual discrimination remain common within orthopaedics. The international orthopaedic community is obliged to do more to tackle this problem.
O47 Safe delivery of surgical tracheostomies in COVID-19 patients during the pandemic
Authors: Angamuthu N , Baker D , Tsui J , Gagasa E , D'Souza R E
Published: July 2021

Introduction

During the corona virus disease (COVID-19) pandemic, frontline units worldwide faced the challenging task of providing high-risk services (like surgical tracheostomy) while safe-guarding the very people performing the high risk procedures. The aim of our study was to assess the incidence of COVID-19 infection among staff involved in surgical tracheostomy on COVID-19 patients

Method

A surgical tracheostomy protocol and operation theatre modifications were put in place at our centre, dictated by local resources, staff availability and previous tracheostomy experience. Between 26/03/2020 and 27/05/2020, staff participating in 71 tracheostomy procedures were sent a questionnaire. The presence of COVID-19 symptoms (new onset continuous cough, fever, loss of taste and/or loss of smell) in tracheostomy staff and patient related data were analysed.

Result

Among the responders (72/122), compliance with personal prophylaxis equipment use was 100%. Eleven (15%,11/72) reported key COVID-19 symptoms and self-isolated. 10 had a COVID-19 swab test and three tested positive. One staff attended (1/72) hospital for symptomatic treatment, none required hospitalisation. 43/72 staff (60%) underwent a COVID-19 antibody test, 18.6% (8/43) were positive. Among the tracheostomised patients, the mean age was 58 years(29–78) and 65.5% were males. The median time from intubation to ST was 15 days (range 5–33, IQR = 9). There were no tracheostomy related deaths and overall mortality was 11%(6/55).

Conclusion

Safe delivery of tracheostomy during a pandemic like COVID-19 is possible with strict adherence to personnel protective equipment, surgical protocols and regulation of traffic flow in theatres to mitigate the potential transmission of COVID-19 among surgical staff.

Take-home Message

Compliance with PPE, adherence to tracheostomy protocol and local modifications can mitigate potential COVID-19 transmission among health care personnel.
O48 Incongruous trends in peripheral arterial disease and amputation in Australia
Authors: Goodall R J , Hughes W R M , Salciccioli J D , Marshall D , Shalhoub J
Published: July 2021

Introduction

We aimed to compare the incidence trends for peripheral arterial disease (PAD) and lower extremity amputation (LEA) in Australia with European Union (EU) 15+ countries.

Method

For the years 1990–2017, we extracted PAOD and LEA incidence data from the Global Burden of Disease (GBD) Study and compared trends across EU15+ countries (19 countries with similar health expenditure—including Australia, the US and the UK).

Result

In 2017, the age-standardised incidence rate (ASIR) for PAOD was lower in Australia than any other EU15+ country for males (90.0/100,000) and third lowest in females (99.9/100,000) (only females in Norway and Spain had lower 2017 ASIRs for PAD). However for LEA, the 2017 ASIRs were higher in Australia for both sexes than in any other EU15+ country (male 119.8/100,000, female 78.0/100,000).

Furthermore, contrasting and anomalous time trends in the incidence of PAOD and LEA were observed in Australia between 1990–2017. The PAOD ASIR decreased over the 28-year period for both males (-16.5%) and females (-17.4%), whereas the LEA ASIR increased over the same time period for both sexes (males +12.5%, females +10.3%). Given the frequency with which LEAs are precipitated by PAOD, these divergent trends were unexpected, especially within a developed country such as Australia.

Conclusion

Our data raises the concern that the true incidence of PAOD in Australia is under-diagnosed, with at-risk patients potentially being recognised late in the disease-process, manifesting as high amputation rates relative to countries with similar health expenditure.

Take-home Message

Australia has anomalous trends in amputation and peripheral arterial disease when compared with other countries with similar health expenditure. Our data raises the concern that the true incidence of PAOD in Australia is under-diagnosed, with at-risk patients potentially being recognised late in the disease-process, manifesting as high amputation rates relative to countries with similar health expenditure.
O49 The use of augmented reality for surgical guidance: an assessment of the human error
Authors: Sharma P R , Brech H , Pérez-Pachón L , Gregory J , Lowe T , Poyade M , Gröning F
Published: July 2021

Introduction

Microsoft HoloLens® is an augmented-reality headset which is increasingly used for surgical guidance. This headset allows the overlay of patient-specific virtual models obtained from medical images onto the patient’s body surface using automatic marker-based alignment. This can guide surgeons during certain surgical tasks, e.g. determining biopsy needle entry points. This study aims to measure the human error in the localisation of virtual models with the headset and discuss its surgical implications.

Method

59 adults were recruited between the ages of 20–59 years. A 12 cm2 digital marker was displayed on a monitor in 9 different positions, one at a time. This was repeated 3 times, resulting in 27 markers shown to each participant. Once a marker was detected by the headset’s camera, a virtual hexagon was rendered on the headset’s transparent lenses. Participants were tasked to click on the hexagon’s vertices using a mouse. The clicks’ coordinates were recorded by the system and compared to the predicted coordinates. This allowed for the calculation of the vertex localisation error.

Result

The mean vertex localisation error was found to be 5.19 mm (±3.56) with a range from 0.08 to 29.77 mm. There was a significant difference between marker positions as determined by a one-way ANOVA (P < 0.001).

Conclusion

This study suggests that the error in the localisation of virtual models depends on the position of the markers relative to the user wearing the headset. Further research is required to explore whether training can reduce the human error with this headset.

Take-home Message

The range of the human error in localising virtual models via the Microsoft HoloLens® headset is large and may be dependent on the position of the marker relative to the user of the headset. Further research is needed to investigate whether training with the headset can improve human performance.
O50 New guidelines to reduce unnecessary blood tests, delayed discharge and costs following robot assisted radical prostatectomy
Authors: Fricker M , Nathan A , Hannah N , Rashid A , Patel S , Phuah Y , Flora K , Cleaveland P , Kasivisvanathan V , Williams N , Miah S , Shah N , Hines J , Collins J , Sridhar A , Kelkar A , Briggs T , Kelly J , Shaw G , Sooriakumaran P , Rajan P , Lamb B , Nathan S
Published: July 2021

Introduction

Routine postoperative blood tests (POBT) are used to evaluate the impact of surgery on pre-existing co-morbidities and to detect early complications. This practice dates back to an era of open surgery, when blood loss and complication rates were higher. We propose new guidelines to improve the specificity of POBT.

Method

The cases of 1040 consecutive patients who underwent a primary or salvage RARP at two large tertiary urology centres in the United Kingdom were retrospectively reviewed, and new guidelines were designed. The guidelines were prospectively validated in a cohort of 300 patients.

Result

Derivation Dataset 3% and 5% had intra- and post-operative Clavien-Dindo complications, respectively. 15% had clinical concerns postoperatively. 0.9% required perioperative transfusion. 78% had routine blood tests without clinical concerns, none of whom developed a complication. 98% of complications were suspected by clinical judgement. 6% of patients had a discharge delay of ≥ 1 days due to delayed or incomplete blood tests.

Validation Dataset No significant difference existed in complication, clinical concern or transfusion rates between the derivation and validation datasets. New guidelines improved sensitivity for complications from 98% to 100% and specificity from 0% to 74%. The number of blood tests requested reduced by 73% (P < 0.001). Discharge delays reduced from 6% to 0% (P = 0.008). Cost savings were £178 per patient.

Conclusion

Postoperative complications and transfusion following RARP are rare. Routine POBT without clinical indication are unnecessary and inefficient. A guideline-based approach to POBT can reduce costs and optimise discharge without compromising patient safety or care.

Take-home Message

Routine postoperative blood tests following robot assisted radical prostatectomy are often unnecessary. A guideline-based approach can reduce costs and optimise patient care.
O51 The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study
Authors: Ita M I , Wang J H , Toulouse A , Lim C H , Fanning N , O’Sullivan M G J , Nolan Y , Kaar G F , Redmond H P
Published: July 2021

Introduction

Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging has been occasioned by the invasive nature of brain tumour biopsy. Circulating-cell-free messenger RNAs are short fragments of RNA present in blood. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma derived RNA.

Method

Blood samples were collected from twenty-nine patients prior to tumour resection. Plasma ccfmRNA and glioma derived RNA were extracted and profiled.

Result

BCL2L1, CXCL5, GZMB, HLA-A, HLA-C, IRF1, MYD88, TGFB1, TLR2, and TP53 genes were significantly over-expressed in glioma (high-grade-glioma-HGG and low-grade-glioma-LGG) patients (P < 0.05, versus control). BCL2L1, GZMB and HLA-A genes were significantly over-expressed in HGG patients (P < 0.05, versus LGG patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma and glioma derived RNA (Spearman r = 0.6344, n = 14, P = 0.017), and with the mean FPKM of TCGA glioma derived RNA samples (Spearman r = 0.4614, n = 19, P = 0.047). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of CSF3 gene (r = 0.9813, n = 20, P < 0.001).

Conclusion

We identified significant differential expression of genes involved in cancer inflammation and immunity among patients with different glioma grades, and we identified positive correlation between the plasma transcriptomic profile and tumour samples, and with TCGA glioma derived RNA.

Take-home Message

The plasma transcriptomic profile of glioma patients appears to be representative of synchronously obtained glioma samples.
O52 Plasma circulating cell-free messenger RNA as a potential biomarker of melanoma
Authors: Ita M. I , Wang J H , Fanning N , Kaar G F , Lim C H , Redmond H P
Published: July 2021

Introduction

Blood-borne cell-free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with therapeutic response.

Method

Plasma circulating cell-free messenger ribonucleic acid (ccfmRNA) was extracted from twenty patients with stage IV melanoma receiving immunotherapy. Pathway focused gene expression analysis was performed. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. Response Evaluation Criteria in Solid Tumours (RECIST 1.1) was used for tumour burden estimation.

Result

In stage IV melanoma patients, CCL5, GZMB and MYD88 genes were significantly over-expressed (P < 0.05 versus healthy controls). In patients with high disease burden or progressive disease, CCL18, CCR1, CCR4, CD274, CSF2, and GBP1 genes were significantly over-expressed (P < 0.05 versus patients with therapeutic response). Finally, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, GBP1, and PTGS2 genes were significantly over-expressed (P < 0.05, versus patients without brain metastasis).

Conclusion

Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma. CCL4 and CCL5 are prognostic in melanoma, both genes had significantly higher expressions in low disease burden patients compared to patients with a high disease burden.

Take-home Message

CCL4 and CCL5 ccfmRNA transcripts are prognostic in melanoma. High expression of both genes is favourable in melanoma patients.
Reproductive Dormancy in Overwintering AdultEucryptorrhynchus brandti(Coleoptera: Curculionidae)
Authors: Guo Wen-juan , Qin Yan-ni , Wen Jun-bao
Published: July 2021

Dormancy is important for overwintering insects to resist and adapt to adverse conditions. Dormancy generally contains quiescence and diapause. Eucryptorrhynchus brandti Harold (Coleoptera: Curculionidae), tree-of-heaven trunk weevil (TTW), is a destructive pest and highly host-specific to Ailanthus altissima in China. TTW has one generation per year and overwinters as both larvae and adults. In this study, to examined dormancy type of adults and find a method to store overwintering adults, we collected adults from 20 October 2018 to 13 March 2019. We studied the behavior and reproductive development of adults under field cold conditions for 0 and 10 d and laboratory warm conditions for 5 and 10 d. We recorded developing eggs in females, and the clarity of the testis edge, the yellow point in the testis lobe, the ratio of the inner content in the accessory gland, and the accessory gland color in males. Adults transferred from the field to the laboratory had resumed reproductive development directly. Results indicated that the dormancy type of TTW adults was quiescence. Adults stored in the field were still in a dormant state and the field-storage method was effective. Current study provided basic data for controlling overwintering TTW adults and solve the storage of insect sources during the winter.
Predicting future left anterior descending artery events from non-culprit lesions: insights from the Lipid-Rich Plaque study
Authors: Kuku Kayode O , Garcia-Garcia Hector M , Doros Gheorghe , Mintz Gary S , Ali Ziad A , Skinner William H , Artis Andre K , ten Cate Tim , Powers Eric , Wong Shing Chiu , Wykrzykowska Joanna , Dube Sandeep , Kazziha Samer , van der Ent Martin , Shah Priti , Sum Stephen , Torguson Rebecca , Di Mario Carlo , Waksman Ron
Published: July 2021

Aims

The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments.

Methods and results

LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93–9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06–6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001).

Conclusion

Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.
Time trends in ischaemic heart disease incidence and mortality over three decades (1990–2019) in 20 Western European countries: systematic analysis of the Global Burden of Disease Study 2019
Authors: Vancheri Federico , Tate Anne Rosemary , Henein Michael , Backlund Lars , Donfrancesco Chiara , Palmieri Luigi , Strender Lars-Erik
Published: July 2021

Aims

To investigate and compare changes in the rates of ischaemic heart disease (IHD) incidence and mortality between 1990 and 2019 in 20 high-income Western European countries with similar public health systems and low cardiovascular risk.

Methods and results

The 2020 updated version of the Global Burden of Disease database was searched. Variability and differences in IHD incidence and mortality rates (per 100 000) between countries over time, were calculated. A piecewise linear (join point) regression model was used to identify the slopes of these trends and the points in time at which significant changes in the trends occur. Ischaemic heart disease incidence and mortality rates varied widely between countries but decreased for all between 1990 and 2019. The relative change was greater for mortality than for incidence. Ischaemic heart disease incidence rates declined by approximately 36% between 1990 and 2019, while mortality declined by approximately 60%. Breakpoint analysis showed that the largest decreases in incidence and mortality occurred between 1990 and 2009 (−32%, −52%, respectively), with a much slower decrease after that (−5.9%, −17.6%, respectively), and even a slight increase for some countries in recent years. The decline in both incidence and mortality was lower in the Mediterranean European countries compared to the Nordic and Central European regions.

Conclusions

In the Western European countries studied, the decline in age-standardized IHD incidence over three decades was slower than the decline in age-standardized IHD mortality. Decreasing trends of both IHD incidence and mortality has substantially slowed, and for some countries flattened, in more recent years.