Quantifying the burden of survivorship associated with infrarenal abdominal aortic aneurysms.

OBJECTIVES: Survivorship encompasses the physical, psychological, social, functional, and economic experience of a living with a chronic condition for both the patient and their caregiver. It is made up of nine distinct domains and remains understudied in nononcological pathologies, including infrarenal abdominal aortic aneurysmal disease (AAA). This review aims to quantify the extent to which existing AAA literature addresses the burden of survivorship. METHODS: The MEDLINE, EMBASE, and PsychINFO databases were searched from 1989 through September 2022. Randomized controlled trials, observational studies, and case series were included. Eligible studies had to detail outcomes related to survivorship in patients with AAA. Owing to the heterogeneity between studies and outcomes, no meta-analysis was conducted. Study quality was assessed with specific risk of bias tools. RESULTS: A total of 158 studies were included. Of these, only five (treatment complications, physical functioning, comorbidities, caregivers, and mental health) of the nine domains of survivorship have been studied previously. The available evidence is of variable quality; most 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. The most frequent complication after EVAR was endoleak. EVAR is associated with poorer long-term outcomes compared with open surgical repair in most studies retrieved. EVAR showed better outcomes in regard to physical functioning in the short term, but this advantage was lost in the long term. The most common comorbidity studied was obesity. No significant differences were found between open surgical repair and EVAR in terms of impact on caregivers. Depression is associated with various comorbidities and increased the risk of a nonhospital discharge. CONCLUSIONS: This review highlights the absence of robust evidence regarding survivorship in AAA. As a result, contemporary treatment guidelines rely on historic quality-of-life data that are narrow in scope and nonrepresentative of contemporary clinical practice. As such, there is an urgent need to reevaluate the aims and methodology associated with traditional quality-of-life research moving forward.

Patient Reported Outcome Measures Used to Assess Quality of Life in Aortic Dissection: a Systematic Scoping Review using COSMIN Methodology.

OBJECTIVE: To systematically identify all patient reported outcome measures (PROMs) (quality of life [QOL] instruments or other instrument/methodology) that have been used to date in aortic dissection (AD) and to explore how well these instruments evaluate QOL according to the Consensus based Standards for the selection of health Measurement Instruments (COSMIN) methodology or guideline. DATA SOURCES: Embase, MEDLINE, PsycINFO, CINAHL, and Cochrane Library were search on 1st July 2022. REVIEW METHODS: This scoping review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and the COSMIN guidelines for performing systematic reviews of validated PROMs. Studies that reported on any aspect or domain of QOL using a PROM or other instrument or methodology on AD were included. Data synthesis, including psychometric property analysis and risk of bias assessment were performed according to COSMIN guidelines. RESULTS: Forty-five studies, published between 1994 and 2021 reporting on 5 874 patients (mean age 63 years, 70.6% male), were included. A total of 39 PROMs were used, and three studies used semi-structured interviews. The majority (69%) of studies were in patients with type A aortic dissection (TAAD). The most common PROM used was the SF-36 (51%). Six studies evaluated one or more psychometric properties of a PROM. Only one of these studies was specifically designed as a validation study. No study reported on content validity. Internal consistency was the most evaluated psychometric property. No study evaluated all the psychometric properties according to COSMIN methodology. The methodological quality used to assess these PROMs was judged to be adequate or very good. CONCLUSION: This review highlights the heterogeneity of PROMs or methods used to determine QOL in AD patients. The lack of research regarding a comprehensive evaluation of the psychometric properties of a PROM used in AD highlights the need for the development and validation of a dissection specific PROM. [PROSPERO registration no. CRD42022310477].

Trends in Hospital Admissions, Operative Approaches, and Mortality Related to Abdominal Aortic Aneurysms in England Between 1998 and 2020.

OBJECTIVE: To assess trends in abdominal aortic aneurysm (AAA) hospital admissions, interventions, and aneurysm related mortality in England, and to examine the impact of endovascular repair on mortality for the years 1998 - 2020. METHODS: Hospital admission and operative approach (endovascular aortic aneurysm repair, or open surgical repair [OSR]) using Hospital Episodes Statistics (HES), and aneurysm related mortality data from the Office for National Statistics for England standardised to the 2013 European Standard Population, were analysed using linear regression and Joinpoint regression analyses. Aneurysm related mortality was compared between the pre-endovascular era (1998 - 2010) and the endovascular era (2011 - 2019). RESULTS: A declining trend in hospital admission incidence was observed, mainly due to a decline in ruptured admissions from 34.6 per 100 000 (95% confidence interval [CI] 33.5 - 35.6) to 13.5 per 100 000 (95% CI 12.9 - 14.2; ßi = -1.04, r2 = .97, p < .001). Operative interventions have been declining over the last 23 years mainly due to the statistically significant decline in open procedures (41.2 per 100 000 in 2000 [95% CI 40 - 42.3] to 9.6 per 100 000 [95% CI 9.1 - 10.1]; ßi = -1.92, r2 = .95; p < .001). There was an increasing trend toward endovascular procedures (5.8 per 100 000 [95% CI 5.3 - 6.2] in 2006 to 16.9 per 100 000 [95% CI 16.2 - 17.5] in 2020; ßi = .82, r2 = .30, p = .040). Reductions in aneurysm related mortality due to AAAs were observed for males and females, irrespective of age and rupture status. CONCLUSION: A significant decrease in hospital admissions for AAAs was observed over the last 23 years in England, paralleled by a shift toward endovascular repair and a decline in OSR. Declines in aneurysm related mortality were observed overall, and in the endovascular era irrespective of age, sex, and rupture status.

Coverage of the Coeliac Artery During Thoracic Endovascular Aortic Repair: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the clinical impact of coeliac artery (CA) coverage during thoracic endovascular aortic repair (TEVAR). METHODS: This systematic review and meta-analysis was conducted according to the PRISMA guidelines. Electronic databases were searched from 1989 to 2020 for studies reporting visceral ischaemia, spinal cord ischaemia (SCI), 30 day/in hospital mortality, endoleaks, re-intervention, and caudal stent graft migration following CA coverage in patients undergoing TEVAR. Meta-analysis was conducted using random effects modelling. The quality of the evidence was graded using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Fifteen observational studies with 236 patients (108 male, age range 61.3 - 79 years) were included. The pooled visceral ischaemia rate was 13% with significant heterogeneity between studies (95% confidence intervals [CI] 4 - 24; I2 = 72%, p < .001). The SCI rate was 5% (95% CI 2 - 9; I2 = 0%); the 30 day/in hospital mortality was 4% (95% CI 1 - 7; I2 = 0%); the overall endoleak rate was 21% (95% CI 13 - 29; I2 = 35%) with a 5% (95% CI 0 - 13; I2 = 38%) rate of type Ib and 2% (95% CI 0 - 8; I2 = 43%) rate of type II endoleak from retrograde CA flow. The re-intervention rate was 13% (95% CI 6 - 22; I2 = 54%); the caudal stent graft migration rate was 3% (95% CI 0 - 9, I2 = 0%). The certainty of the body of evidence was judged to be very low for all outcomes. CONCLUSION: CA coverage during TEVAR is associated with high rates of visceral ischaemia, spinal cord ischaemia, 30 day/in hospital mortality, endoleaks, and re-intervention. Although the literature is of poor quality and questions remain over effects estimates, there is evidence that CA coverage should be avoided if at all possible, during TEVAR. REGISTRATION: PROSPERO registration number 244084.

Trends in Thoracic Aortic Aneurysm Hospital Admissions, Interventions, and Mortality in England between 1998 and 2020: An Observational Study.

OBJECTIVE: To assess trends in thoracic aortic aneurysm (TAA) hospital admissions, interventions, and aneurysm related mortality (ARM) in England, and examine the impact of endovascular repair on mortality for the years 1998 to 2020. METHODS: Hospital admission and operative approach (thoracic endovascular aortic repair, [TEVAR] or open surgical repair) using Hospital Episodes Statistics, and ARM data from the Office for National Statistics for England standardised to the 2013 European Standard Population were analysed using linear regression and Joinpoint regression analyses. ARM was compared between the pre-endovascular era (1998 - 2008) and the endovascular era (2009 - 2019). RESULTS: A rising trend in hospital admission incidence has been observed, mainly due non-ruptured admissions (4.11 per 100 000 in 1998; 95% confidence interval (CI) 3.71 - 4.50 to 12.61 per 100 000 in 2020; 95% CI 12.00 - 13.21 in 2020; r2 = .98; p < .001). Operative interventions increased mainly due to an increase in TEVAR (2.15 per 100 000; 95% CI 1.91 - 2.41 in 2020 vs. 0.26 per 100 000; 95% CI 0.16 - 0.36 in 2006; r2 = .90; p < .001). Reductions in ARM from TAA were observed for males and females, irrespective of age and rupture status. The greatest reduction in ARM in the endovascular era was observed in females aged > 80 years with ruptured disease (15.26 deaths per 100 000 vs. 9.50 deaths per 100 000; p < .001). CONCLUSION: A significant increase in hospital admissions for non-ruptured TAA has been observed in the last 23 years in England, paralleled by a shift towards endovascular repair, and significant declining trends in ARM, irrespective of sex and age. The significant reductions in age standardised death rates from ruptured and non-ruptured TAA in the endovascular era, particularly for females aged > 80 years with ruptured disease, affirm the positive impact of an endovascular approach to TAA.

Four-year results of the Bolton relay proximal scallop endograft in the management of thoracic and thoracoabdominal aortic pathology with unfavorable proximal landing zone.

BACKGROUND: Thoracic endovascular aortic repair with a scallop design (scallop-TEVAR) is a useful treatment strategy to extend the proximal landing zone (PLZ), while maintaining perfusion to one or more of the supra-aortic trunks (SATs) when treating aortic pathology with an unfavorable PLZ. The durability of this approach with the Bolton Relay scallop endograft (Terumo Aortic, Sunrise, Fla) has not been established. METHODS: A retrospective review of prospectively collected data on consecutive patients that received scallop-TEVAR in zones 0 to 2 at a tertiary aortic unit was undertaken. The main outcome was durability, characterized by survival estimates, freedom from reintervention to the thoracic aorta and PLZ, migration and aneurysm sac regression. RESULTS: Between 2009 and 2019, 38 patients (71% male; median age, 70 years) underwent scallop-TEVAR for thoracic aortic pathology (n = 28, 74%) or as a part of thoracoabdominal aneurysm repair (n = 10 [26%]). The use of scallop-TEVAR significantly extended the PLZ (median, 5 mm preoperative PLZ vs 26 mm extended PLZ; P = .0001). A total of 41 SATs were perfused with a scallop, including the left subclavian artery (n = 25), left common carotid artery (n = 6), neo/innominate artery (n = 4), left subclavian artery, and vertebral artery (n = 1), innominate artery, and left common carotid artery (n = 2) in conjunction with 15 extra-anatomical bypasses. The PLZ was at Ishimaru zone 0 and 1 in 6 cases (16%), respectively, and zone 2 in 26 cases (68%). Technical success was 98%. The 30-day mortality was 5% (2/38; 1 death from myocardial infarction and 1 from multiorgan failure). A minor stroke occurred in three patients (8%) and temporary spinal cord ischemia in two patients (5%). The median follow-up was 4.5 years (range, 0-10.53 years) during which two patients (5%) developed type Ia endoleak and required intervention to the PLZ (one from device-related migration and one from disease progression). All-cause and aorta-related survival were 72% and 85% and freedom from thoracic and PLZ reintervention was 92% and 97%, respectively. There were no cases of early or late thoracic aortic rupture, retrograde type A aortic dissection or SAT occlusion. CONCLUSIONS: Scallop-TEVAR offers a less invasive treatment option to extend the seal zone in selected patients with an unfavorable PLZ, allowing for a durable repair in terms of overall survival and reintervention. Periprocedural stroke remains a principle concern.

Colour as a signal for entraining the mammalian circadian clock.

Twilight is characterised by changes in both quantity ("irradiance") and quality ("colour") of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.

Geniculohypothalamic GABAergic projections gate suprachiasmatic nucleus responses to retinal input.

KEY POINTS: Visual input to the suprachiasmatic nucleus circadian clock is critical for animals to adapt their physiology and behaviour in line with the solar day. In addition to direct retinal projections, the clock receives input from the visual thalamus, although the role of this geniculohypothalamic pathway in circadian photoreception is poorly understood. In the present study, we develop a novel brain slice preparation that preserves the geniculohypothalamic pathway to show that GABAergic thalamic neurons inhibit retinally-driven activity in the central clock in a circadian time-dependent manner. We also show that in vivo manipulation of thalamic signalling adjusts specific features of the hypothalamic light response, indicating that the geniculohypothalamic pathway is primarily activated by crossed retinal inputs. Our data provide a mechanism by which geniculohypothalamic signals can adjust the magnitude of circadian and more acute hypothalamic light responses according to time-of-day and establish an important new model for future investigations of the circadian visual system. ABSTRACT: Sensory input to the master mammalian circadian clock, the suprachiasmatic nucleus (SCN), is vital in allowing animals to optimize physiology and behaviour alongside daily changes in the environment. Retinal inputs encoding changes in external illumination provide the principle source of such information. The SCN also receives input from other retinorecipient brain regions, primarily via the geniculohypothalamic tract (GHT), although the contribution of these indirect projections to circadian photoreception is currently poorly understood. To address this deficit, in the present study, we established an in vitro mouse brain slice preparation that retains connectivity across the extended circadian system. Using multi-electrode recordings, we first confirm that this preparation retains intact optic projections to the SCN, thalamus and pretectum and a functional GHT. We next show that optogenetic activation of GHT neurons selectively suppresses SCN responses to retinal input, and also that this effect exhibits a pronounced day/night variation and involves a GABAergic mechanism. This inhibitory action was not associated with overt circadian rhythmicity in GHT output, indicating modulation at the SCN level. Finally, we use in vivo electrophysiological recordings alongside pharmacological inactivation or optogenetic excitation to show that GHT signalling actively modulates specific features of the SCN light response, indicating that GHT cells are primarily activated by crossed retinal projections. Taken together, our data establish a new model for studying network communication in the extended circadian system and provide novel insight into the roles of GHT-signalling, revealing a mechanism by which thalamic activity can help gate retinal input to the SCN according to time of day.

Is transanal total mesorectal excision a reproducible and oncologically adequate technique? A pilot study in a single center.

PURPOSE: An oncologically effective total mesorectal excision (TME) still represents a technical challenge, especially in the presence of a low rectal cancer and anatomical restraints such as obesity or narrow pelvis. Recently, few reports have shown that transanal TME was feasible and associated with good outcomes. Nevertheless, a widespread employment of the technique has yet to happen due to the doubts about the reproducibility of the results outside a tertiary specialized center. METHODS: Between February 2014 and June 2015, patients with low rectal cancer underwent a transanal TME with laparoscopic assistance. The end points included the oncologic adequacy of the mesorectal excision and the perioperative outcomes. RESULTS: Eleven patients (9 male, median age 70.5 years) with proven low rectal cancer were enrolled in the study. The median distance of the tumor from the anal verge was 5 cm (2-7). Four patients (36.4 %) received preoperative chemoradiation. The median operative time was 360 min (275-445). Postoperative morbidity (36.4 %) included one (9.1 %) anastomotic leak requiring a reoperation. The median length of hospital stay was 8 days (3-28). The median distance from the circumferential and distal resection margins were, respectively, 5 (1-20) and 10 (5-20) mm, and the mean number of harvested lymph nodes was 21.7 (11-50). All cases had a complete or nearly complete mesorectal plane of surgery. CONCLUSIONS: Although technically challenging, the initial results suggest that transanal TME could be a feasible, oncologically safe, and reproducible operation. However, more robust studies are required to assess the short- and long-term outcomes.

Prognostic and predictive value of ultrasound-based estimated ankle brachial pressure index at early follow-up after endovascular revascularization of chronic limb-threatening ischaemia: a prospective, single-centre, service evaluation.

Background: Ankle brachial pressure index can be estimated (eABPI) using cuffless ankle Doppler ultrasound. We evaluated the prognostic value of eABPI measured during pre- and post-procedural ultrasound exams to predict the clinical outcome after endovascular revascularisations. Methods: In this prospective, single-centre, service evaluation, consecutive patients with symptomatic peripheral artery disease undergoing lower limb endovascular revascularisations between July, 26 2018 and January, 13 2022 at Surrey and Sussex Healthcare NHS Trust (Redhill, UK) were analysed. eABPI was determined using the higher acceleration index measured with angle-corrected duplex ultrasound in ankle arteries before and ≤1 month post-procedure. Clinical outcomes (mortality, major amputations, amputation-free survival [AFS], clinically driven target lesion revascularization [cdTLR], major adverse limb events [MALE; cdTLR and major amputation], wound healing) were assessed over 1 year. Findings: Of 246 patients treated, for 219 patients (median 75 [IQR 66-83] years) pre- and post-procedural eABPI (0.50 [0.33-0.59] and 0.90 [0.69-1.0], p < 0.0001) were available, respectively. In n = 199 patients with chronic limb-threatening ischaemia (CLTI) Kaplan-Meier survival analyses showed that higher post-procedural, but not pre-procedural, eABPI was associated with favourable AFS, MALE, cdTLR, and wound healing. This was confirmed in Cox regression analysis and remained significant with adjustment for pre-procedural eABPI, age, sex, co-morbidities, treated levels, wound score, and foot infection. Whereas all clinical outcomes, except for survival, were significantly better at ≥0.7 vs <0.7, wound healing (unadjusted: HR 1.7 (95% CI 1.2-2.6), adjusted: HR 2.1 (95% CI 1.3-3.1), cdTLR, and MALE (unadjusted: HR 0.41 (95% CI 0.18-0.93), adjusted: HR 0.28 (95% CI 0.11-0.74) were significantly improved at ≥0.9 vs <0.9. Interpretation: Post-procedural eABPI can provide valid, clinically important prognostic and predictive information. Our data indicate that revascularisations should target values of at least 0.9 to achieve optimal outcomes. Future studies need to confirm generalisability and cost-effectiveness in a wider context. Funding: European Partnership on Metrology, co-financed from European Union's Horizon Europe Research and Innovation Programme and UK Research and Innovation.

Carbon dioxide flushing versus saline flushing of thoracic aortic stents (INTERCEPTevar): protocol for a multicentre pilot randomised controlled trial.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) carries a 3%-6.1% stroke risk, including risk of 'silent' cerebral infarction (SCI). Stent-grafts are manufactured in room air and retain air. Instructions for use recommend saline flushing to 'de-air' the system prior to insertion, but substantial amounts of air are released when deploying them, potentially leading to downstream neuronal injury and SCI. Carbon dioxide (CO2) is more dense and more soluble in blood than air, without risk of bubble formation, so could be used in addition to saline to de-air stents. This pilot trial aims to assess the feasibility of a full-scale randomised controlled trial (RCT) investigating the neuroprotective benefit against SCI with the use of CO2-flushed aortic stent-grafts. METHODS AND ANALYSIS: This is a multicentre pilot RCT, which is taking place in vascular centres in the UK, USA and New Zealand. Patients identified for TEVAR will be enrolled after informed written consent. 120 participants will be randomised (1:1) to TEVAR-CO2 or TEVAR-saline, stratified according to TEVAR landing zone. Participants will undergo preoperative neurocognitive tests and quality of life assessments, which will be repeated at 6 weeks, or first outpatient appointment, and 6 months. Inpatient neurological testing will be performed within 48 hours of return to level 1 care for clinical stroke or delirium. Diffusion-weighted MRI will be undertaken within 72 hours postoperatively (1-7 days) and at 6 months to look for evidence and persistence of SCI. Feasibility will be assessed via measures of recruitment and retention, informing the design of a full-scale trial. ETHICS AND DISSEMINATION: The study coordination centre has obtained approval from the London Fulham Research Ethics Committee (19/LO/0836) and Southern Health and Disability Ethics Committee (NZ) and UK's Health Regulator Authority (HRA). The study has received ethical approval for recruitment in the UK (Fulham REC, 19/LO/0836), New Zealand (21/STH/192) and the USA (IRB 019-264, Ref 378630). Consent for entering into the study will be taken using standardised consent forms by the local study team, led by a local PI. The results of the trial will be submitted for publication in an open access journal. TRIAL REGISTRATION NUMBER: NCT03886675.

Risk Prediction Models for Peri-Operative Mortality in Patients Undergoing Major Vascular Surgery with Particular Focus on Ruptured Abdominal Aortic Aneurysms: A Scoping Review.

PURPOSE: The present scoping review aims to describe and analyze available clinical data on the most commonly reported risk prediction indices in vascular surgery for perioperative mortality, with a particular focus on ruptured abdominal aortic aneurysm (rAAA). MATERIALS AND METHODS: A scoping review following the PRISMA Protocols Extension for Scoping Reviews was performed. Available full-text studies published in English in PubMed, Cochrane and EMBASE databases (last queried, 30 March 2023) were systematically reviewed and analyzed. The Population, Intervention, Comparison, Outcome (PICO) framework used to construct the search strings was the following: in patients with aortic pathologies, in particular rAAA (population), undergoing open or endovascular surgery (intervention), what different risk prediction models exist (comparison), and how well do they predict post-operative mortality (outcomes)? RESULTS: The literature search and screening of all relevant abstracts revealed a total of 56 studies in the final qualitative synthesis. The main findings of the scoping review, grouped by the risk score that was investigated in the original studies, were synthetized without performing any formal meta-analysis. A total of nine risk scores for major vascular surgery or elective AAA, and 10 scores focusing on rAAA, were identified. Whilst there were several validation studies suggesting that most risk scores performed adequately in the setting of rAAA, none reached 100% accuracy. The Glasgow aneurysm score, ERAS and Vancouver score risk scores were more frequently included in validation studies and were more often used in secondary studies. Unfortunately, the published literature presents a heterogenicity of results in the validation studies comparing the different risk scores. To date, no risk score has been endorsed by any of the vascular surgery societies. CONCLUSIONS: The use of risk scores in any complex surgery can have multiple advantages, especially when dealing with emergent cases, since they can inform perioperative decision making, patient and family discussions, and post hoc case-mix adjustments. Although a variety of different rAAA risk prediction tools have been published to date, none are superior to others based on this review. The heterogeneity of the variables used in the different scores impairs comparative analysis which represents a major limitation to understanding which risk score may be the "best" in contemporary practice. Future developments in artificial intelligence may further assist surgical decision making in predicting post-operative adverse events.

Understanding the Impact of COVID-19 on Angioplasty Service and Outcome of Patients Treated for Chronic Limb-Threatening Ischaemia: A Single-Centre Retrospective Cohort Study.

We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of chronic limb-threatening ischaemia (CLTI) patients undergoing lower-limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018-02/2020), 106 CLTI patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020-07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%), and hospitalised patients decreased. Patients treated in ≤14/5 days after referral significantly increased to 64/63%. Kaplan-Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target-lesion revascularisation decreased during COVID-19. One-year mortality was significantly worse in hospitalised compared to day cases (14% vs. 43%) at similar wound healing rates (83% vs. 84%). The most frequent known cause of death was infectious disease (64%), while cardiovascular (21%) was less frequent. Despite COVID-19 restrictions, a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLTI patients need to be referred and treated more aggressively earlier.

Study of novel selective mGlu2 agonist in the temporo-ammonic input to CA1 neurons reveals reduced mGlu2 receptor expression in a Wistar substrain with an anxiety-like phenotype.

Group II metabotropic receptors (mGluRs) regulate central synaptic transmission by modulating neurotransmitter release. However, the lack of pharmacological tools differentiating between mGlu2 and mGlu3 receptors has hampered identification of the roles of these two receptor subtypes. We have used LY395756 [(1SR,2SR,4RS,5RS,6SR)-2-amino-4-methylbicyclo[3.1.0]-hexane2,6-dicarboxylic], an agonist at mGlu2 receptors and an antagonist at mGlu3 receptors in cell lines, to investigate the roles of these receptors in the temporo-ammonic path from entorhinal cortex to CA1-stratum lacunosum moleculare in rat hippocampal slices. Surprisingly, the degree of inhibition of the field EPSP induced by LY395756 fell into two distinct groups, with EC(50) values of <1 µm and >100 µm. In "sensitive" slices, LY395756 had additive actions with a mixed mGlu2/mGlu3 agonist, DCG-IV [(2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine], whereas in "insensitive" slices, LY395756 reduced the effect of DCG-IV, with an IC(50) of ∼1 µm. This separation into sensitive and insensitive slices could be explained by LY395756 acting as an mGlu2 agonist and mGlu3 antagonist, respectively, a finding supported by data from mice lacking these receptors. The heterogeneity was correlated with differences in expression levels of mGlu2 receptors within our Wistar colony and other Wistar substrains. The initial search for a behavioral correlate indicated that rats lacking mGlu2 receptors showed anxiety-like behavior in open-field and elevated plus maze assays. These findings have implications for rat models of psychiatric disease and are especially pertinent given that mGlu2 receptors are targets for compounds under development for anxiety.

The Haemodynamic and Pathophysiological Mechanisms of Calcific Aortic Valve Disease.

The aortic valve (AoV) is the outflow valve for the left heart [...].

Misinformation About the Human Gut Microbiome in YouTube Videos: Cross-sectional Study.

BACKGROUND: Social media platforms such as YouTube are integral tools for disseminating information about health and wellness to the public. However, anecdotal reports have cited that the human gut microbiome has been a particular focus of dubious, misleading, and, on occasion, harmful media content. Despite these claims, there have been no published studies investigating this phenomenon within popular social media platforms. OBJECTIVE: The aim of this study is to (1) evaluate the accuracy and reliability of the content in YouTube videos related to the human gut microbiome and (2) investigate the correlation between content engagement metrics and video quality, as defined by validated criteria. METHODS: In this cross-sectional study, videos about the human gut microbiome were searched for on the United Kingdom version of YouTube on September 20, 2021. The 600 most-viewed videos were extracted and screened for relevance. The contents and characteristics of the videos were extracted and independently rated using the DISCERN quality criteria by 2 researchers. RESULTS: Overall, 319 videos accounting for 62,354,628 views were included. Of the 319 videos, 73.4% (n=234) were produced in North America and 78.7% (n=251) were uploaded between 2019 and 2021. A total of 41.1% (131/319) of videos were produced by nonprofit organizations. Of the videos, 16.3% (52/319) included an advertisement for a product or promoted a health-related intervention for financial purposes. Videos by nonmedical education creators had the highest total and preferred viewership. Daily viewership was the highest for videos by internet media sources. The average DISCERN and Health on the Net Foundation Code of Conduct scores were 49.5 (SE 0.68) out of 80 and 5.05 (SE 2.52) out of 8, respectively. DISCERN scores for videos by medical professionals (mean 53.2, SE 0.17) were significantly higher than for videos by independent content creators (mean 39.1, SE 5.58; P<.001). Videos including promotional materials had significantly lower DISCERN scores than videos without any advertisements or product promotion (P<.001). There was no correlation between DISCERN scores and total viewership, daily viewership, or preferred viewership (number of likes). CONCLUSIONS: The overall quality and reliability of information about the human gut microbiome on YouTube is generally poor. Moreover, there was no correlation between the quality of a video and the level of public engagement. The significant disconnect between reliable sources of information and the public suggests that there is an immediate need for cross-sector initiatives to safeguard vulnerable viewers from the potentially harmful effects of misinformation.

The diagnostic and triage accuracy of digital and online symptom checker tools: a systematic review.

Digital and online symptom checkers are an increasingly adopted class of health technologies that enable patients to input their symptoms and biodata to produce a set of likely diagnoses and associated triage advice. However, concerns regarding the accuracy and safety of these symptom checkers have been raised. This systematic review evaluates the accuracy of symptom checkers in providing diagnoses and appropriate triage advice. MEDLINE and Web of Science were searched for studies that used either real or simulated patients to evaluate online or digital symptom checkers. The primary outcomes were the diagnostic and triage accuracy of the symptom checkers. The QUADAS-2 tool was used to assess study quality. Of the 177 studies retrieved, 10 studies met the inclusion criteria. Researchers evaluated the accuracy of symptom checkers using a variety of medical conditions, including ophthalmological conditions, inflammatory arthritides and HIV. A total of 50% of the studies recruited real patients, while the remainder used simulated cases. The diagnostic accuracy of the primary diagnosis was low across included studies (range: 19-37.9%) and varied between individual symptom checkers, despite consistent symptom data input. Triage accuracy (range: 48.8-90.1%) was typically higher than diagnostic accuracy. Overall, the diagnostic and triage accuracy of symptom checkers are variable and of low accuracy. Given the increasing push towards adopting this class of technologies across numerous health systems, this study demonstrates that reliance upon symptom checkers could pose significant patient safety hazards. Large-scale primary studies, based upon real-world data, are warranted to demonstrate the adequate performance of these technologies in a manner that is non-inferior to current best practices. Moreover, an urgent assessment of how these systems are regulated and implemented is required.

Ankle Doppler for Cuffless Ankle Brachial Index Estimation and Peripheral Artery Disease Diagnosis Independent of Diabetes.

Ankle brachial pressure index (ABPI) is the first-line test to diagnose peripheral artery disease (PAD). Its adoption in clinical practice is poor and its validity, particularly in diabetes, is limited. We hypothesised that ABPI can be accurately and precisely estimated based on cuffless Doppler waveforms. Retrospective analysis of standard ABPI and handheld Doppler waveform characteristics (n = 200). Prospective analysis of angle-corrected Doppler acceleration index (AccI, n = 148) and standard ABPI with testing of performance to diagnose PAD as assessed with imaging reference standards in consecutive patients. The highest AccI from handheld Doppler at ankle arteries was significantly logarithmically associated with the highest standard ABPI (E[y] = 0.32 ln [1.71 ∗ x + 1], p < 0.001, R2 = 0.68, n = 100 limbs). Estimated ABPI (eABPI) based on AccI closely resembled ABPI (r = 0.81, p < 0.001, average deviation −0.01 ± 0.13 [SD], n = 100 limbs). AccI from angle-corrected Doppler in patients without overt media sclerosis (ABPI ≤ 1.1) improved ABPI prediction (E[y] = 0.297 ∗ ln[0.039 ∗ x + 1], R2 = 0.92, p = 0.006, average deviation 0.00 ± 0.08, n = 100). In a population (n = 148 limbs) including diabetes (56%), chronic limb-threatening ischaemia (51%) and media sclerosis (32%), receiver operating characteristics analysis of (angle-corrected) eABPI performed significantly better than standard ABPI to diagnose PAD defined by ultrasound (ROC AUC = 0.99 ± 0.01, p < 0.001; sensitivity: 97%, specificity: 96%) at the ≤0.9 cut-off. This was confirmed with CT angiography (ROC AUC = 0.98, p < 0.001, sensitivity: 97%, specificity: 100%) and was independent of the presence of diabetes (p = 0.608). ABPI can be estimated based on ankle Doppler AccI without compression, and eABPI performs better than standard ABPI to diagnose PAD independent of diabetes. eABPI has the potential to be included as a standard component of lower extremity ultrasound.