bluuebunny/crossref_metadata_2025 huggingface dataset:
O073 Patient-reported outcome measures (PROMS) used to assess quality of life (QOL) in aortic dissection: a systematic scoping review using COSMIN methodology
Authors: Jha R , Hanna L , Sounderajah V , Makar S , Gibbs R
Published: May 2023

Introduction

Objective: to identify and evaluate all patient reported outcome measures (PROMS) using the established Consensus-based Standard for the selection of health Measurement Instruments (COSMIN) guidelines.

Methods

A scoping systematic review was conducted for studies that used a PROM in aortic dissection (AD) patients according to PRISMA-Scr, using electronic databases and grey literature.

Results

45 studies were found, encompassing 38 PROMs. The most common PROM utilised was the 36-Item Short-Form Survey (SF-36), used in 23 studies. The majority of the remainder PROMs however (30/38) were only utilised once in their respective studies, with no disease-specific tool identified. 6 studies further evaluated a psychometric property of 4 PROMs (PROMIS-29, SF-36, SWL and SWED-QUAL). Only 1 of these studies was a PROM validation study, with the remaining 5 only reporting on internal consistency. None of the studies assessed content validity. The methodological quality for all 6 papers was judged to be adequate or very good, however, the quality of evidence was judged to be low, with none of the PROMs having undergone a rigorous psychometric evaluation within the AD population.

Conclusion

This review identified severe heterogeneity in the PROMs used to assess the QOL of AD patients. These instruments are generic and lack any formal content validity evaluation. A validated dissection-specific tool for use in clinical practice is therefore required to better understand and improve QOL in this patient cohort.

PROMIS-29 – Patient Reported Outcome Measure Information System

SWL – Satisfaction With Life scale

SWED-QUAL – Swedish Health-Related Quality of Life Scale
O075 Pausing NHSBSP during COVID-19 did not increase advanced cancers and may have avoided overdiagnosis
Authors: Aquilina R , Vaidya J , Varghese J
Published: May 2023

Introduction

We ascertained the impact of the paused NHS breast cancer screening programme (NHSBSP) during COVID-19 on number and presentation of breast cancer patients.

Methods

We analysed, breast cancer patients diagnosed across 2 large London NHS trust hospitals in sets: the referral source and numbers in all patients from 2019 to 2021 (n=3,353), and patient/tumour characteristics and treatments received during 6 selected months in 2019 and 2020 (n=318). We analysed proportions using chi-square test.

Results

Overall, there were 31% fewer patients in 2020 compared with 2019 (1281 vs 886, p=0.002). However, there was no corresponding increase in the number of patients during 2021 (n=1186). The reduction was mainly due to fewer referrals from NHSBSP rather than from GPs (53% reduction vs 13%, p<0.00001). In 2020 vs 2019, there were fewer grade 1 (35 vs 9) and node negative tumours (143 vs 72), without a corresponding increase in grade 2 or 3 (159 vs 104), or node positive cases (54 vs 49); also fewer T1 cases (84 to 37) without a corresponding increase in >T1 cases (113 vs 84); reduced breast conservations (111 vs 71) and negative sentinel nodes (114 vs 69), without increase in mastectomies (35 vs 25) or axillary clearances (32 vs 27). There were no receptor status changes.

Conclusion

The COVID-19 pause in NHSBSP avoided diagnosis of good prognosis cancers without rapid increase in worse prognosis cancers or more extensive surgery, suggesting that it may have simply avoided overdiagnosis.
O084 A preoperative breath test to predict post-oesophagectomy pulmonary infection
Authors: Mitra A , Das B , Tarazi M , Lafaurie G , Arya P , Leung K , Converso V , Parker A , Hanna G
Published: May 2023

Introduction

Pulmonary infection (PI) is the most common complication post-oesophagectomy. Identifying patients at risk of PI could facilitate pre-emptive preventative measures. Analysis of exhaled volatile organic compounds (VOCs) is a novel method of diagnosing disease non-invasively. Given the integral contribution of the oro-respiratory system in generating breath VOCs, this study applied breathomics to develop a novel predictive model for PI prior to oesophagectomy.

Methods

Breath samples were collected from patients with oesophageal adenocarcinoma on the morning of their surgery using a quality-controlled methodologically optimised workflow. Breath was analysed using two gold standard analytical platforms: one (GC-MS) and two-dimensional (GCxGC-MS) thermal-desorption gas-chromatography time-of-flight mass-spectrometry, the latter being unrivalled in its chromatographic resolution. Raw spectral data was pre-processed and analysed using a tile-based Fisher ratio method to generate predictive models. Ethical approval REC: 17/WA/0161.

Results

Breath samples were analysed from 23 patients undergoing oesophagectomy and 12 (52%) developed PI. Principal component analysis revealed significantly distinct volatolomes discriminating PI risk status (R2Xcum 0.908, Q2cum 0.806, CV ANOVA p<0.001). A 5 VOC model had an area under the curve of 0.806 (95%CI 0.647-0.947) and 0.859 (95%CI 0.601-1) for predicting PI using GC-MS and GCxGC-MS respectively. Predictive VOCs were tentatively identified to be branched chain in structure suggesting a likely microbial origin.

Conclusion

This is the first predictive PI model using state-of-the-art breathomics. Identification of branched chain VOCs offers unprecedented insights into the disease biology of post-oesophagectomy PI and highlights an important role of the preoperative oro-respiratory microbiome as a risk factor for PI.
O093 Manipulating the hypoxia induced radioresistance in rectal cancer
Authors: Fok M , Fok M , Fowler H , Clifford R , Hill R , Grundy G , Parsons J , Vimalachandran D
Published: May 2023

Introduction

Locally advanced rectal cancer is primarily treated with radiotherapy and chemotherapy. Tumour hypoxia induces strong radioresistance, although the reasons for this characteristic are still unclear. This research explores the mechanistic and biological factors underlying hypoxia-induced radioresistance, and development of novel therapeutic strategies to overcome this.

Methods

HCT116 and HT29 CRC cell lines were incubated in normoxia (21% O2) and hypoxic conditions (1% O2). Cells were irradiated at varying dosages of x-ray radiation before undergoing clonogenic survival assay, comet assay to assess DNA double strand break damage and repair, or immunobloting to investigate cell death-related factors. HIF1α and HIF1b siRNA knockdowns were used to assess radioresponse in hypoxia. Metformin was used to treat cells prior to radiation and assess cell survival.

Results

Hypoxia induces strong radioresistance in CRC cells compared to relative normoxia in clonogenic survival assays. Neutral comet assays showed no significant difference in double strand break (DSB) repair kinetics following irradiation in hypoxia compared to normoxia. Immunoblotting analysis demonstrates activation of hypoxia-inducible factor 1a (HIF1a) in hypoxia but not in normoxia. HIF1α and HIF1b siRNA knockdowns did not show any improvement in radioresistance. Metformin did not improve radiosensitivity of CRC cells under different oxygen conditions.

Conclusion

Hypoxia induces strong radioresistance in cultured CRC cells which is not explained by x-ray-induced DSB damage and the efficiency of its repair. HIF1a is activated in hypoxia alone and may contribute to this resistance. Metformin alone is unable to overcome this resistance and other therapeutic targets need to be explored.
O111 Defining humanitarian surgery: an international Delphi process
Authors: McKnight G , Friebel R , Marks I , Almaqadma A , Salem M , Tientcheiu T , Saleh R , Ryan-Coker M , Emodi R , Seida M , Barden J , Leather A , Hargest R
Published: May 2023

Introduction

Over the last decade there has been an exponential increase in the terms “global surgery” and “humanitarian surgery”. However, the terms are often used interchangeably and there is no fixed definition of ‘humanitarian surgery’. This makes it difficult to compare interventions, outcomes and cost effectiveness since a wide variety of activities are included in these global or humanitarian surgery programmes.

Methods

A Delphi process was used over 3 rounds using online software to facilitate responses. A core set of academics and global surgery leaders were invited by targeted email and a snowball sampling effect was used to target responses form Low/Middle Income Countries. Predetermined inclusion criteria were used to ensure the validity of respondents. A Likert scale of 1-6 was used, group agreement was indicated by a median of 3 4 and group consensus was indicated by an interquartile range of £ 2. Intraclass correlation was used to assess stability of response.

Results

Round 1 generated 25 statements, across 4 themes: Who, What, Where and When. Of these, 10 reached agreement and consensus after Rounds 2 and 3. These 10 statements were then used as the basis for the definition of ‘Humanitarian Surgery’.

Conclusion

By agreeing the definition of ‘Humanitarian Surgery’, this will allow comparison of activities within the field to ensure they are appropriate, provide a high quality of care and are cost effective. Debate should now move to focus on ensuring Humanitarian Surgery is delivered to the highest possible standard wherever and whenever it is required.
O132 Preliminary results of radiofrequency ablation for haemorrhoidal disease at a district general hospital
Authors: Win M , Ngo V , Rajaganeshan R
Published: May 2023

Introduction

Haemorrhoidal disease (HD) is a common perianal condition. There is still limited data on the role of minimally invasive surgery for HD. The aim of our study was to report the outcome of radiofrequency ablation of haemorrhoids under local anaesthetic (RAFAELO) at our institution.

Methods

23 patients who had a day-case RAFAELO procedure under local anaesthesia without sedation by a single surgeon from March to October 2022 were retrospectively reviewed. We analysed patients’ demographics, haemorrhoid severity score (HSS), the health's condition scale in EQ-5D-5L questionnaire, and recurrence rate.

Results

The mean age of patients was 50 years (SD 14). 65% were male whereas 35% were female. Majority of haemorrhoids (48%) were Grade 3A. Most of the cases had previous procedures such as rubber band ligation (57%) and hemorrhoidal dearterialization (9%). Only 34% had no prior hemorrhoidal surgery. The mean HSS score significantly improved from 13.2 (SD 4.9) to 4 (SD 2.2) with p < 0.001 postoperatively. The health's condition scale became significantly lower from 64 (SD 23.6) to 23.9 (SD 14.6) with p < 0.001. The median length of follow up was 2 months (range 1-5 months). There was no acute postprocedural complication but there was a recurrence rate of 13% requiring further procedures.

Conclusion

This study supports previous findings that RAFAELO is a safe and effective procedure for HD. It also highlights that it can be performed in the out-patient setting safely. However, further studies with larger samples, longer follow-up and comparison with other procedures are suggested.
O135 Efferent limb stimulation prior to loop ileostomy closure- a meta-analysis
Authors: Lloyd A , Hardy N , Hechtl D , Toale J , Clancy C , Whelan M , O’Riordan J , Kavanagh D , Sahebally S
Published: May 2023

Introduction

Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. We aimed to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced the incidence of POI.

Methods

A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases from inception until Oct 2022, was performed. All studies comparing PPS versus no stimulation were included. The primary objective was the incidence of POI whilst secondary objectives included time to resume oral diet, nasogastric tube (NGT) placement postoperatively, time to first passage of flatus/stool, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Sensitivity analyses were also performed.

Results

Four studies (3 randomized, 1 prospective) capturing 293 patients (140 PPS, 153 no-stimulation) were included. The PPS group was associated with a lower POI incidence (10.7 vs. 26.8%, OR 0.27, 95%CI=0.09-0.86, p=0.03), quicker time to resume oral diet (MD -1.34 days, p=0.02), shorter LOS (MD -1.43 days, p=0.001) and fewer complications (OR 0.37, p=0.008). However, there was no difference in the requirement for NGT placement (OR 0.50, p=0.12) or time to first passage of flatus/stool (MD -0.71 days, p=0.24). On sensitivity analysis, focusing on randomized data only, the difference observed in POI rates was lost (OR 0.35, p=0.10) whereas the results of the secondary objectives prevailed.

Conclusion

Efferent limb stimulation prior to surgery appears to result in a quicker time to resume oral diet, shorter LOS but similar POI rates. Further studies are needed to confirm those findings.
O136 An observational cohort study of replicate faecal immunochemical tests in symptomatic two-week wait patients
Authors: Farkas N , O’Brien J , Whyte M , Jourdan I , Rockall T , Benton S
Published: May 2023

Introduction

Triage of patients with suspected colorectal cancer (CRC) utilises a single faecal immunochemical test (FIT) at a defined threshold. Limited evidence exists regarding whether replicate FIT improves the positive and negative predictive value in symptomatic patients. This study examines two-week wait (TWW) patients undergoing replicate FIT. Primary aim is to assess two FITs and CRC/serious bowel disease. Secondary aims are to determine correlation and utility of replicate FIT.

Methods

TWW patients carried out one additional FIT during COVID-19 pandemic. FIT 1 and FIT 2 (the replicate sample) were analysed in relation to symptoms, diagnoses, investigations, future colonoscopy and missed CRC. Study period was 01/03/2020-31/07/2020. Three subgroups were compared; double positive (>10μg Hb/g faeces), double negative, and discordant FIT (one positive).

Results

111 patients had replicate FIT (50 male, 61 female). 43 (38.7%) patients had double negative, 32 (28.8%) double positive and 36 (32.4%) had discordant FITs. Median time between FITs was 14 days (IQR=11 to 19). 83% of double positive patients underwent colonoscopy/virtual colonoscopy (61% in double negative patients). Six CRC and one high-risk polyp were in double positive patients (none in other groups). One discordant patient was not investigated and a CRC missed.

Conclusion

Replicate FIT as a triage strategy appears most effective where both FITs are negative. CRC risk is low when FIT results are discordant. Double negative FITs are reassuring given benign associated diagnoses, or for patients where endoscopic investigation is high-risk. Larger studies are required to evaluate discordant FITs, enabling refinement of urgent investigation pathways.
O138 Diagnostic and prognostic factors associated with faecal haemoglobin concentration in a symptomatic cohort
Authors: Farkas N , O'Brien J , Norman J , Steinke J , Yu K , Jourdan I , Rockall T , Benton S
Published: May 2023

Introduction

There is limited evidence regarding FIT and colorectal cancer (CRC) site, stage, grade and anaemia in the symptomatic cohort. Primary aim is to determine whether an association exists between FIT (analysed with OC-Sensor™ Pledia) and these diagnostic/prognostic factors. Secondary aim was to compare continuous versus categorical FIT, to determine the difference when reporting to upper limit of quantification (some centres do not report FIT >200 (μg Hb/g faeces)).

Methods

Symptomatic two-week wait CRC with FIT were grouped into thresholds (<10, 10-200 and >200) and analysed using Chi-squared test. Mann-Whitney U test (p≤0.05) compared median FIT in sex, stage, grade and site (right-sided (R-CRC): caecum to transverse colon/ left-sided (L-CRC): splenic flexure to rectum). Pearson's correlation compared FIT and continuous variables (haemoglobin, mean corpuscular volume and ferritin).

Results

114 patients (57F:57M); 46 R-CRC (FIT=113) vs 68 L-CRC (FIT=342) (p=0.07), 69 moderately differentiated CRC (FIT=183) vs 29 poorly differentiated (FIT=866) (p=0.004). 35 early stage (T1/2) (FIT=170) vs 79 advanced (T3/4) (FIT=200) (p=0.06). Ferritin <30ug/L correlated with higher FIT (p=0.18). When grouped into FIT thresholds, each association became less significant.

Conclusion

Left-sided, poorly differentiated and advanced stage CRC is associated with higher FIT. There appears benefit in reporting FIT to the upper limit of quantification in symptomatic patients, as this may allow greater differentiation and earlier investigation of those with adverse CRC prognostic features. The presence of low ferritin reinforces the diagnostic value of elevated FIT. Given these findings, FIT may have a role in risk stratification for CRC beyond diagnosis alone.
O140 Delorme vs. Altemeier: a systematic review and meta-analysis comparing the common perineal procedures for rectal prolapse
Authors: Bhattacharya P , Zaman S , Hussain M I , Peravali R
Published: May 2023

Introduction

Rectal prolapse is a particularly distressing condition for patients, and there is no consensus yet as to the best surgical option for treatment. In this systematic review and meta-analysis we compared the outcomes for the two most commonly employed perineal operations for rectal prolapse – Delorme's and Altemeier's procedure.

Methods

A systematic search of multiple electronic databases was conducted. Peri- and post-operative outcomes following Delorme's and Altemeier's procedures were extracted. Primary outcomes included recurrence rate, anastomotic leak rate, and length of hospital stay. The secondary outcomes were operation time, volume of blood loss and length of hospital stay. Revman 5.3 was used to perform statistical analysis.

Results

10 studies including a total of 605 patients were selected. Recurrence (OR: 0.66; 95% CI [0.44–0.99], P= 0.05) and anastomotic leak (RD: 0.05; 95% CI [0.00–0.09], P= 0.03) were found to be significantly less in the Altemeier group than in the Delorme group. However on subgroup analysis Altemeiers with plasty (perineoplasty or levatoroplasty) failed to show significant differences in comparison to Delorme's. Hospital stay was significantly more after Altemeiers procedure than after Delorme procedure (MD: 3.05, 95% CI [0.95–5.51], p=0.004). No significant difference was found with respect to operative time, intra operative blood loss and mortality rates.

Conclusion

Our study indicates that between the two common perineal procedures, Altemeier's operation has better outcomes. Future high quality RCTs with long follow up are required to corroborate these findings.
O151 A comparison of pathological TNM 7 with TNM 8 staging for pancreatic ductal adenocarcinoma and distal cholangiocarcinoma
Authors: Mohammad F , Hanks M , Kandiah K , Wong T , Adiamah A , Zaitoun A M , Lobo D N
Published: May 2023

Background

The 8th edition of the TNM (tumour, nodes and metastasis) staging system was introduced in 2016 to improve the prognostic prediction of pancreatic ductal adenocarcinoma (PDAC). However, its superiority over the previous edition remains uncertain. This study evaluated the prognostic impact of TNM 7 with TNM 8 staging in patients with PDAC and distal cholangiocarcinoma.

Methods

A retrospective cohort study was conducted using electronic healthcare databases at a tertiary hepatobiliary centre in the UK. Kaplan-Meier survival curves were used to evaluate the prognostic prediction of TNM 7 and TNM 8 staging. The concordance index was calculated to assess the discriminatory power of both systems. Crosstabulation of T, N and overall staging was performed to determine which staging system stratified patients more effectively.

Results

The study identified 194 patients and found the overall median survival after resection to be 1.86 years. The concordance index for TNM 7 [0.634; 95% confidence intervall(CI) 0.586-0.682)], was similar to TNM 8 (0.633; 95% CI 0.584-0.683). TNM 8 showed improved stratification of patients for the T (p=0.001), N (p=0.001) classifications and overall staging system (p=0.001). However, in TNM 8, the new N2 stage had a similar survival prediction to N1.

Conclusion

There was no significant difference in the prognostic prediction between the TNM 7 and TNM 8 systems for PDAC and distal cholangiocarcinoma. While TNM 8 improved patient stratification across T staging, our findings found the introduction of the N2 staging to be unnecessary as its survival prediction was comparable to N1.
O156 A systematic review of ethical considerations in paediatric bariatric surgery
Authors: Shah A , Kumar N S
Published: May 2023

Introduction

With childhood obesity prevalence increasing rapidly, bariatric surgery is being given greater consideration in the paediatric population. Paucity of long-term evidence, physical and emotional risks, and reliance on parental decision-making are factors constituting this moral complexity, forming debate around eligibility and timing of offering the procedure. Consequently, a systematic review was conducted to evaluate ethical considerations.

Methods

All relevant synonyms of paediatric, bariatric surgery and ethics were used to identify papers for inclusion in the systematic review and reference lists were scanned. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to.

Results

10 papers were included. A key ethical dilemma frequently explored was the issue of consent, and ensuring the child is at the forefront of the decision. Paediatric bariatric surgery causes controversy as children are exposed to surgical risk early in life, and thus prolonged preventative measures are encouraged with the aim to mitigate obesity by adulthood causing unnecessary harm. Children without a strong support network have additional obesity risk, whereby withholding surgery may be viewed as inequitable and non-beneficent. There is also conflict between delaying surgery until the child is Fraser-competent versus increased complication risk.

Conclusion

Further evidence to guide assessment criteria are needed to facilitate informed consent. Post-operative support should be audited, with inclusive care and sustained health outcomes monitored. Although preventative methods are important in the paediatric population, clinicians must not discriminate against those for whom it proves ineffective, with bariatric surgery being a last resort for high-risk obese patients.
O162 Can digital microscopes be used in microsurgery simulation training?
Authors: Awad L , Langridge B , Butler P
Published: May 2023

Introduction

Surgical education has seen a transition in the delivery of training, with increased use of online platforms to facilitate remote learning. Simulation provides a safe training environment, that can be accessed by a wider group, and at a lower cost compared to many ex-vivo courses. Microsurgical skills are difficult to acquire, and continuous practice is necessary to improve. Our goals are to compare commercially available digital microscopes against a standard binocular microscope and review their suitability for bench model simulation.

Methods

Data was collected for three commercially available digital microscopes, and a binocular table microscope. Data obtained included physicial properties, cost and a subjective assessment of their surgical performance via an 11 criteria questionnaire, graded with a 5-point scale. Results of the commercial microscopes were compared with the binocular microscope using the Kruskall Wallis test.

Results

The questionnaire was completed by 21 participants ranging from senior ENT/Plastic Surgery consultants to core surgical trainees. Digital microscopes were more affordable and convenient for trainees. The Pancellant Digital Microscope performed the poorest, with trainees commenting on its unsuitability for surgical practice. The Plugable USB Microscope was rated most like the binocular table microscope. Depth of field was shallow in all digital microscopes.

Conclusion

With the increasing role of remote learning and simulation training in surgical education, the Plugable USB digital microscope can provide a cheaper, more accessible alternative for junior trainees, in their pursuit of microsurgical skill acquisition.
P12 Patient-specific automated cerebrospinal fluid pressure control to augment spinal wound closure: a case series using LiquoGuard®
Authors: Khan D , Tariq K , Lee K , Dyson E , Russo V , Watkins L , Russo A
Published: May 2023

Introduction

Post-operative spinal cerebrospinal fluid (CSF) leaks are a common and potentially serious surgical complication. The management of intra- and post-operative leaks is heterogeneous. Numerous studies advocate for dural repair and CSF diversion. The LiquoGuard7 allows automated and precise CSF pressure and volume control, with the calculation of patient-specific biometrics. We sought to summarize our experience with patient-specific CSF automated drainage with layered spinal wound closure.

Methods

This single-centre case series included patients undergoing complex spinal surgery where: 1) a high-flow intra- and/or postoperative CSF leak was expected and 2) concurrent CSF diversion was performed via lumbar drain attached to a LiquoGuard7®. CSF diversion was tailored to calculated CSF production rates and other case factors to maintain a neutral pressure across the operative site.

Results

Three patients were included, with a variety of pathologies (T7/T8 disc prolapse; T8-T9; T4-T5 metastatic spinal cord compression). The first two patients underwent CSF diversion to prevent post-op CSF leak, whilst case 3 required this in response to post-op CSF leak. CSF hyperproduction (140-150ml/hr) was evident in all cases. With patient-specific CSF diversion regimes, no cases required further intervention for CSF fistulae repair (including for pleural CSF effusion), wound breakdown or infection.

Conclusion

Automated patient-specific cerebrospinal fluid drainage may have a role in the closure of complex spinal wounds with high-flow CSF leaks, with a smaller risk profile than traditional manual drainage. Further larger studies are needed to explore the comparative benefits and cost-effectiveness of these devices.
P18 Components of the ideal spoke vascular surgery unit
Authors: Faisal M J , Baker D , Agu O , Benaragama K S
Published: May 2023

Introduction

The ‘Hub and Spoke’ system consists of a leading unit that offers all services (Hub), supported by peripheral units providing less extensive services (Spokes). Cases requiring more complex interventions are often transferred from Spoke Units to the Hub. We wish to shed light on the factors that comprise an ideal Spoke Unit.

Methods

We did a retrospective review of the Peripheral arterial and Venous cases at our Spoke unit, and analysed patient records, took note of the contributions of various specialities and teams within the unit, allowing us to provide optimal care.

Results

We found that over an 8-month period (5th April 2022- 1st December 2022), the spoke unit undertook 105 lower limb venous procedures, and 55 arterial revascularisations, as day cases. This was possible due to the support we have from the podiatrists, vascular scientists, interventional radiologists, anaesthesiologists, physiotherapists, clinical specialist nurses and allied nursing teams as well as vascular unit managers. In cases where the hub may be overburdened, the Spoke unit can provide support by managing patients within their domain. Our main Hub Unit has an estimated capacity of 70-80 patients per week at any given time. When referrals to the Hub exceed the capacity, the spoke unit supports them to ensure optimal patient care and avoid physician burnout.

Conclusion

Having a strong multidisciplinary team contributes to an ideal spoke unit. Creating the ideal spoke unit is essential to optimise patient healthcare within a Hub and Spoke system, but also in preventing physician burnout.
Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers
Authors: Taylor Caitlin M , Furman Daniella J , Berry Anne S , White Robert L , Jagust William J , D’Esposito Mark , Jacobs Emily G
Published: May 2023

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women’s hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women’s health.
Dynamic signatures of the Eureka effect: an EEG study
Authors: Lu Yiqing , Singer Wolf
Published: May 2023

The Eureka effect refers to the common experience of suddenly solving a problem. Here, we study this effect in a pattern recognition paradigm that requires the segmentation of complex scenes and recognition of objects on the basis of Gestalt rules and prior knowledge. In the experiments, both sensory evidence and prior knowledge were manipulated in order to obtain trials that do or do not converge toward a perceptual solution. Subjects had to detect objects in blurred scenes and indicate recognition with manual responses. Neural dynamics were assessed with high-density Electroencephalography (EEG) recordings. The results show significant changes of neural dynamics with respect to spectral distribution, coherence, phase locking, and fractal dimensionality. The Eureka effect was associated with increased coherence of oscillations in the alpha and theta bands over widely distributed regions of the cortical mantle predominantly in the right hemisphere. This increase in coherence was associated with decreased beta power over parietal and central regions and with decreased alpha power over frontal and occipital areas. In addition, there was a right hemisphere-lateralized reduction of fractal dimensionality. We propose that the Eureka effect requires cooperation of cortical regions involved in working memory, creative thinking, and the control of attention.
Brain potentials reveal how emotion filters native language access when bilinguals read words in their second language
Authors: Zhang Wanyu , Jończyk Rafał , Wu Yan Jing , Lan Yuxin , Gao Zhao , Hu Jiehui , Thierry Guillaume , Gao Shan
Published: May 2023

It is now well established that reading words in a second language (L2) automatically activates native language (L1) translations in bilinguals. Although there is evidence that access to such representations is inhibited when words have a negative emotional valence, the mechanism underlying such inhibition is elusive, and it is unknown whether inhibition arises online as L2 is being processed or whether negative valence affects subsequent L1 processing. Here, we recorded event-related brain potentials in Chinese-English bilinguals engaged in an implicit translation-priming paradigm involving L2 (English) word pairs. Participants performed a semantic relatedness task, unaware that word pairs could conceal a sound repetition if translated into Chinese. When emotional valence was manipulated in prime position (first word), we observed form repetition priming through L1 translations for positive but not for negative words. However, when emotional valence was manipulated in target position (second word), priming occurred for both positive and negative word valences. This result begins to elucidate the mechanism by which emotion regulates language processing in bilinguals: Negative words in L2 induce a refractory period during which cross-language lexical access is blocked. These findings show that despite being neuroanatomically distinct in the human brain, emotional (limbic) regulation systems can penetrate language processing.
Hippocampal theta activity during encoding promotes subsequent associative memory in humans
Authors: Joensen Bárður H , Bush Daniel , Vivekananda Umesh , Horner Aidan J , Bisby James A , Diehl Beate , Miserocchi Anna , McEvoy Andrew W , Walker Matthew C , Burgess Neil
Published: May 2023

Hippocampal theta oscillations have been implicated in associative memory in humans. However, findings from electrophysiological studies using scalp electroencephalography or magnetoencephalography, and those using intracranial electroencephalography are mixed. Here we asked 10 pre-surgical epilepsy patients undergoing intracranial electroencephalography recording, along with 21 participants undergoing magnetoencephalography recordings, to perform an associative memory task, and examined whether hippocampal theta activity during encoding was predictive of subsequent associative memory performance. Across the intracranial electroencephalography and magnetoencephalography studies, we observed that theta power in the hippocampus increased during encoding, and that this increase differed as a function of subsequent memory, with greater theta activity for pairs that were successfully retrieved in their entirety compared with those that were not remembered. This helps to clarify the role of theta oscillations in associative memory formation in humans, and further, demonstrates that findings in epilepsy patients undergoing intracranial electroencephalography recordings can be extended to healthy participants undergoing magnetoencephalography recordings.
Safety, Tolerability, and Pharmacokinetics of JNJ-1802, a Pan-serotype Dengue Direct Antiviral Small Molecule, in a Phase 1, Double-Blind, Randomized, Dose-Escalation Study in Healthy Volunteers
Authors: Ackaert Oliver , Vanhoutte Frédéric , Verpoorten Nathalie , Buelens Annemie , Lachau-Durand Sophie , Lammens Lieve , Hoetelmans Richard , Van Loock Marnix , Herrera-Taracena Guillermo
Published: May 2023

Background

Dengue is a growing global health threat with no specific antiviral drugs available for treatment or prophylaxis. This first-in-human, double-blind, randomized, placebo-controlled study aimed to examine the safety, tolerability, and pharmacokinetics of increasing single and multiple oral doses of JNJ-1802, a pan-serotype dengue antiviral small molecule.

Methods

Eligible healthy participants (18–55 years of age) were randomized to receive oral JNJ-1802 in fasted conditions as (1) single doses (50–1200 mg; n = 29) or placebo (n = 10); or (2) once-daily doses (50–560 mg for 10 consecutive days or 400 mg for 31 days; n = 38) or placebo (n = 9). Safety and tolerability were evaluated throughout the study. Plasma and urine samples were collected at predetermined time points to characterize pharmacokinetics.

Results

JNJ-1802 was generally safe and well-tolerated. One grade 3 adverse event (depression) was reported but not considered drug-related by the investigator. Two grade 2 events of rash occurred (multiple-dose part) that were considered very likely related to JNJ-1802 by the investigator and resolved. No clinically relevant changes were observed in laboratory tests, electrocardiograms, or vital signs.

JNJ-1802 exposure after single or multiple doses increased dose-proportionally from 50 to 150 mg and less than dose-proportionally for higher doses. The terminal elimination half-life was 6.3–9.2 days and the accumulation factor was 4.3–7.3 after 10 days and 14.6 after 31 days with low amounts of unchanged drug in urine (<0.001% of the 400 mg dose).

Conclusions

Pharmacokinetics and safety results of JNJ-1802 support further clinical development for the treatment and prevention of dengue infection.
TRSRD: a database for research on risky substances in tea using natural language processing and knowledge graph-based techniques
Authors: Wang Yongmei , Wang Peng , Zhang Yongheng , Yao Siyi , Xu Zhipeng , Zhang Youhua
Published: May 2023

During the production and processing of tea, harmful substances are often introduced. However, they have never been systematically integrated, and it is impossible to understand the harmful substances that may be introduced during tea production and their related relationships when searching for papers. To address these issues, a database on tea risk substances and their research relationships was constructed. These data were correlated by knowledge mapping techniques, and a Neo4j graph database centered on tea risk substance research was constructed, containing 4189 nodes and 9400 correlations (e.g. research category-PMID, risk substance category-PMID, and risk substance-PMID). This is the first knowledge-based graph database that is specifically designed for integrating and analyzing risk substances in tea and related research, containing nine main types of tea risk substances (including a comprehensive discussion of inclusion pollutants, heavy metals, pesticides, environmental pollutants, mycotoxins, microorganisms, radioactive isotopes, plant growth regulators, and others) and six types of tea research papers (including reviews, safety evaluations/risk assessments, prevention and control measures, detection methods, residual/pollution situations, and data analysis/data measurement). It is an essential reference for exploring the causes of the formation of risk substances in tea and the safety standards of tea in the future.

Database URL http://trsrd.wpengxs.cn
Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19
Authors: Zuckerberg Jeremy C , Matsubara Daisuke , Kauffman Hunter L , Chang Joyce C , Calderon-Anyosa Renzo , Patel Chandni , Hogarty Alexa N , Falkensammer Christine B , Mercer-Rosa Laura M , Quartermain Michael D , Wang Yan , Banerjee Anirban
Published: May 2023

Aims

We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C).

Methods and results

We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (−)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e′ from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e′LAPeakStrain (%−1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%−1 vs. 0.17%−1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%−1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%−1 for identifying myocardial injury.

Conclusion

In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.
How can progression be predicted in patients with mild to moderate aortic valve stenosis?
Authors: Seo Jeong Hun , Kim Kang Hee , Chun Kwang Jin , Lee Bong-Ki , Cho Byung-Ryul , Ryu Dong Ryeol
Published: May 2023

Aims

The pressure increase per time unit (dP/dt) in aortic stenosis (AS) jet velocity is assumed to have inter-individual variability in the progressive AS stage. We sought to examine the association of aortic valve (AoV) Doppler-derived dP/dt in patients with mild to moderate AS with risk of progression to severe disease.

Methods and results

A total of 481 patients diagnosed with mild or moderate AS [peak aortic jet velocity (Vmax) between 2 and 4 m/s] according to echocardiographic criteria were included. AoV Doppler-derived dP/dt was determined by measuring the time needed for the pressure to increase at a velocity of the AoV jet from 1 m/s to 2 m/s. During a median follow-up period of 2.7 years, 12 of 404 (3%) patients progressed from mild to severe AS and 31 of 77 (40%) patients progressed from moderate to severe AS. AoV Doppler-derived dP/dt had a good ability to predict risk of progression to severe AS (area under the curve = 0.868) and the cut-off value was 600 mmHg/s. In multivariable logistic regression, initial AoV calcium score (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.18–2.73; P = 0.006) and AoV Doppler-derived dP/dt (aOR, 1.52/100 mmHg/s higher dP/dt; 95% CI, 1.10–2.05; P = 0.012) were associated with progression to severe AS.

Conclusion

AoV Doppler-derived dP/dt above 600 mmHg/s was associated with risk of AS progression to the severe stage in patients with mild to moderate AS. This may be useful in individualized surveillance strategies for AS progression.
Thymectomy in severe (Myasthenia Gravis Foundation of America classes IV–V) generalized myasthenia gravis: is the game really worth the candle?
Authors: Brascia Debora , Lucchi Marco , Aprile Vittorio , Guida Melania , Ricciardi Roberta , Rea Federico , Comacchio Giovanni Maria , Schiavon Marco , Marino Maria Carlotta , Margaritora Stefano , Meacci Elisa , Spagni Gregorio , Evoli Amelia , Lorenzoni Giulia , De Iaco Giulia , De Palma Angela , Marulli Giuseppe
Published: May 2023

OBJECTIVES

Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy.

METHODS

Data on 76 MG patients with preoperative MGFA classes IV and V who underwent thymectomy were retrospectively collected. Primary end points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA Post-Intervention Status criteria.

RESULTS

There were 27 (35.5%) males and 49 (64.5%) females; 53 (69.7%) were classified as MGFA class IV and 23 (30.3%) as class V. Thymectomy was performed through sternotomy in 25 (32.9%) patients, Video-assisted thoracic surgery (VATS) in 5 (6.6%) and Robot-assisted thoracic surgery (RATS) in 46 (60.5%). The median operative time was 120 (interquartile range: 95; 148) min. In-hospital mortality was observed in 1 (1.3%) patient and postoperative complications in 14 (18.4%) patients. The median postoperative hospital stay was 4 (interquartile range: 3; 6) days. Pathological examination revealed 31 (40.8%) thymic hyperplasia/other benign and 45 (59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5 years and 66.9% and 97.6% at 10 years, respectively. A significant improvement rate was found in patients with age at the time of thymectomy of ≤50 years (P = 0.0236), MGFA class V (P = 0.0154) and acetylcholine receptor antibodies positivity (P = 0.0152).

CONCLUSIONS

Thymectomy in patients with severe MG yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ MG.
From notes to writing: three students in focus
Authors: Siegel Joseph
Published: May 2023

Taking notes while listening not only aids comprehension and concentration in the moment but also creates an external storage repository of information for later use. As the number of students taking content courses in their L2 in English medium instruction contexts grows, L2 notetaking abilities are beginning to receive much-needed pedagogic and research attention. Students use their notes for a variety of post-listening activities, one of which is writing assignments. The present paper examines the relationship between notes taken by three L2 English students while listening to an academic English text, and writing tasks based on the notes taken. Quantitative and qualitative analysis of the written tasks are presented and discussed in light of note content, providing insights as to how notes are used to generate post-listening writing tasks. Pedagogic implications related to the note-writing task relationship stemming from the findings are presented.
Carotid ultrasound and systematic coronary risk assessment 2 in the prediction of cardiovascular events
Authors: Bao Xue , Xu Biao , Lind Lars , Engström Gunnar
Published: May 2023

Aims

Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is a state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2.

Methods and results

Carotid plaque presence and intima media thickness (IMT) were measured with ultrasound. The SCORE2 was calculated in 4588 non-diabetic participants aged 46–68 years. The incremental value for predicting CVD events of adding carotid plaque or IMT to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The predicted 10-year CVD risk by SCORE2 and the observed event rate were compared between participants with and without carotid plaque. Adding plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvements in C-statistics, IDI, and NRI of adding plaque to SCORE2 for events occurring during the first 10 years were 2.20%, 0.70%, and 46.1%, respectively (all P < 0.0001). The SCORE2 over-predicted the 10-year CVD risk in those without carotid plaque (3.93% observed vs. 5.89% predicted, P < 0.0001) while under-predicted the risk in those with carotid plaque (9.69% observed vs. 8.12% predicted, P = 0.043).

Conclusion

Carotid ultrasound adds predictive performance to SCORE2 for assessment of CVD risk. Using SCORE2 without considering carotid atherosclerosis could under- or over-estimate the risk.

Lay Summaries

Subclinical carotid atherosclerosis is an important consideration in cardiovascular risk estimation by Systematic Coronary Risk Assessment 2 (SCORE2). Carotid ultrasound adds predictive performance to SCORE2 for assessment of cardiovascular risk. SCORE2 over-predicted the 10-year cardiovascular risk in those without carotid plaque while under-predicted the risk in those with carotid plaque.