Impact of nondiameter aortic indices on surgical eligibility: Results from the Treatment in Thoracic Aortic Aneurysm: Surgery Versus Surveillance (TITAN: SvS) randomized controlled trial.

OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.

Real-World Outcomes for the Fifth-Generation Balloon Expandable Transcatheter Heart Valve in the United States.

BACKGROUND: The fifth-generation SAPIEN 3 Ultra Resilia valve (S3UR) incorporates several design changes as compared with its predecessors, the SAPIEN 3 (S3) and SAPIEN 3 Ultra (S3U) valves, including bovine leaflets treated with a novel process intended to reduce structural valve deterioration via calcification, as well as a taller external skirt on the 29-mm valve size to reduce paravalvular leak (PVL). The clinical performance of S3UR compared with S3 and S3U in a large patient population has not been previously reported. OBJECTIVES: The aim of this study was to compare S3UR to S3/S3U for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR). METHODS: Patients enrolled in the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between January 1, 2021, and June 30, 2023, who underwent TAVR with S3UR or S3U/S3 valve platforms were propensity-matched and evaluated for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes. RESULTS: 10,314 S3UR patients were propensity matched with 10,314 patients among 150,539 S3U/S3 patients. At 30 days, there were no statistically significant differences in death, stroke, or bleeding, but a numerically higher hospital readmission rate in the S3UR cohort (8.5% vs 7.7%; P = 0.04). At discharge, S3UR patients exhibited significantly lower mean gradients (9.2 ± 4.6 mm Hg vs 12.0 ± 5.7 mm Hg; P < 0.0001) and larger aortic valve area (2.1 ± 0.7 cm2 vs 1.9 ± 0.6 cm2; P < 0.0001) than patients treated with S3/S3U. The 29-mm valve size exhibited significant reduction in mild PVL (5.3% vs 9.4%; P < 0.0001). CONCLUSIONS: S3UR TAVR is associated with lower mean gradients and lower rates of PVL than earlier generations of balloon expandable transcatheter heart valve platforms.

Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

Long-term outcomes for hybrid aortic arch repair.

OBJECTIVE: Since its inception in the early 2000s, hybrid arch repair (HAR) has evolved from novel approach to well-established treatment modality for aortic arch pathology in appropriately selected patients. Despite this nearly 20-year history of use, long-term results of HAR remain to be determined. As such, objectives of this study are to detail the long-term outcomes for HAR within an expanded classification scheme. METHODS: From August 2005 to August 2022, 163 consecutive patients underwent HAR at a single referral institution. Operative approach was selected according to an institutional algorithm and included zone 0/1 HAR in 25% (n = 40), type I HAR in 34% (n = 56), and type II/III HAR in 41% (n = 67). Specific zone 0/1 technique was zone 1 HAR in 31 (78%), zone 0 with innominate snorkel (zone 0S HAR) in 7 (18%), and zone 0 with single side-branch endograft (zone 0B HAR) in 2 (5%). The 30-day and long-term outcomes, including overall and aortic-specific survival, as well as freedom from reintervention, were assessed. RESULTS: The mean age was 63 ± 13 years and almost one-half of patients (47% [n = 77]) had prior sternotomy. Presenting pathology included degenerative aneurysm in 44% (n = 71), residual dissection after prior type A repair in 38% (n = 62), chronic type B dissection in 12% (n = 20), and other indications in 6% (n = 10). Operative outcomes included 9% mortality (n = 14) at 30 days, 5% mortality (n = 8) in hospital, 4% stroke (n = 7), 2% new dialysis (n = 3), and 2% permanent paraparesis/plegia (n = 3). The median follow-up was 44 month (interquartile range, 12-84 months). Overall survival was 59% and 47% at 5 and 10 years, respectively, whereas aorta-specific survival was 86% and 84% at the same time points. At 5 and 10 years, freedom from major reintervention was 92% and 91%, respectively. Institutional experience had a significant impact on both early and late outcomes: comparing the first (2005-2012) and second (2013-2022) halves of the series, 30-day mortality decreased from 14% to 1% (P = .01) and stroke from 6% to 3% (P = .62). Improved operative outcomes were accompanied by improved late survival, with 78% of patients in the later era vs 45% in the earlier era surviving to 5 years. CONCLUSIONS: HAR is associated with excellent operative outcomes, as well as sustained protection from adverse aortic events as evidenced by high long-term aorta-specific survival and freedom from reintervention. However, surgeon and institutional experience appear to play a major role in achieving these superior outcomes, with a five-fold decrease in operative mortality and a two-fold decrease in stroke rate in the latter half of the series. These long-term results expand on prior midterm data and continue to support use of HAR for properly selected patients with arch disease.

Informing the use of a supplementary immunisation programme for the management of a community cluster of invasive meningococcal disease, Yorkshire, 2022.

OBJECTIVES: To outline the management of a community cluster of serogroup B invasive meningococcal disease (IMD) cases, including key factors for decision making and the choice and implementation of control measures. STUDY DESIGN: Descriptive report of cluster management. METHODS: Subtyping of IMD cases identified a number of potentially linked cases in a defined geographical area. An Incident Management Team (IMT) was convened to coordinate the public health response. A case definition was developed in order to identify further cases within the cluster. RESULTS: Four cases of IMD met the case definition and were initially considered as part of this cluster. Three resided in the same small town, which was the focus for public health management. The IMT agreed that it would be proportionate to instigate additional control measures. The population at higher risk of infection were identified, and a supplementary vaccination programme was rolled out in the community. Over five clinics, 45.6% (639/1401) of the target cohort received at least one dose of the vaccine, with 34.7% (486/1401) receiving both doses. Inequalities in uptake were observed by sex, age and deprivation. CONCLUSIONS: Decision making for public health responses to IMD clusters is complex. Informed by epidemiological evidence, numerous partners engaged in collaborative decision making, which was critical for the effective implementation of the community response. Links between the local authority public health team and the community enabled the use of existing structures and relationships to maximise the number of vaccinations delivered. No further cases of IMD linked to this cluster were identified.

Mid-term outcomes of aortic valve repair using an anatomically shaped internal annuloplasty ring.

OBJECTIVES: The Hemispherical Aortic Annuloplasty Reconstructive Technology (HAART) ring is a rigid, internal and geometric device. The objective of this article is to assess the mid-term outcomes of aortic valve repair (AVr) using this prosthesis. METHODS: A prospectively maintained database was used to obtain outcomes for adult patients undergoing AVr using the HAART ring between September 2017 and June 2023. All aortic patients at our institution undergo life-long surveillance with regular assessment and valve imaging. RESULTS: Seventy-one patients underwent AVr using the HAART device: 53 had a trileaflet valve and 18 a bicuspid valve. The median age was 54 years, and most were male (79%). Many required concomitant intervention: 46% had a root procedure and 77% an arch repair. There were no in-hospital deaths, and the median postoperative stay was 5 days. At a mean follow-up of 3.9 (±1.1) years, freedom from reoperation was 94%. Late imaging demonstrated: zero trace (25%), 1+ (54%), 2+ (15%) and 4+ (6%) aortic insufficiency (AI). Eleven patients have ≥moderate AI under surveillance, all of whom have a trileaflet valve (21% of trileaflet patients). Four patients required reoperation: 3 for ring dehiscence and 1 for endocarditis. CONCLUSIONS: Although early results using the HAART device are encouraging, mid-term results raise concern as 21% of trileaflet patients developed recurrent ≥moderate AI by 4 years post-repair. We experienced 3 incidences of ring dehiscence requiring reoperation. Based on this, we recommend caution using the sub-annular approach for stabilization in patients with trileaflet aortic valves. Long-term results are needed to assess outcomes against established techniques.

COVID-19 associated with universities in England, October 2020-February 2022.

OBJECTIVES: The aim of this study was to describe the epidemiology of COVID-19 cases at universities in England (October 2020-February 2022) and investigate factors associated with rates of COVID-19 among students during autumn/winter of 2021/22. STUDY DESIGN: The study was an observational retrospective study using routine contact tracing data. METHODS: Estimates of COVID-19 cases among students and staff at universities were described. Student cases aged 18-24 years were calculated as a percentage of all cases within that age group. Count regression was used to explore university characteristics associated with case numbers. RESULTS: We identified 102,382 cases among students and 28,639 among staff. Student cases reflected trends in the wider population of the same age group, but the observed fraction aged 18-24 years who were students was consistently below the expected level (32%). Phased reopening of universities in March-May 2021 was associated with small peaks but low absolute numbers. Russell group membership, campus universities, and higher student proportions in halls of residence were all associated with increased case numbers. CONCLUSIONS: COVID-19 case numbers among students in England varied considerably. At no time were the observed case numbers as high as expected from community prevalence. Characteristics of universities associated with higher case rates can inform future guidance for higher education settings.

Retrograde Cerebral Perfusion May Decrease Stroke Risk During Elective Aortic Arch Surgery.

OBJECTIVE: Controversy remains regarding the optimal neuroprotection strategy for elective hemiarch replacement (HEMI). This study sought to compare outcomes in patients who underwent HEMI utilizing the 2 most common contemporary methods of cerebral protection. METHODS: The ARCH international aortic database was queried, and 782 patients undergoing elective HEMI with circulatory arrest from 2007 to 2012 were identified. There were 418 patients who underwent HEMI using moderate hypothermia (nasopharyngeal temperature 20.1 to 28.0 °C) and antegrade cerebral perfusion (MHCA/ACP). There were 364 patients who underwent HEMI using deep hypothermia (nasopharyngeal temperature 14.1 to 20 °C) and retrograde cerebral perfusion (DHCA/RCP). Adverse outcomes were compared between the groups using both univariable and multivariable analyses. RESULTS: Patients who underwent MHCA/ACP were older (64 vs 61 years, P = 0.01) and more frequently had peripheral vascular disease than DHCA/RCP patients (28.5% vs 7.1%, P < 0.001). Patients in the DHCA/RCP group had a greater incidence of full aortic root replacement (55.8% vs 26.4%, P < 0.001) and more frequently had a central cannulation strategy (83% vs 55.7%, P < 0.001). Cardiopulmonary bypass (170 vs 157 min, P = 0.002) and aortic cross-clamp (134 vs 92 min, P < 0.001) times were significantly longer in the DHCA/RCP group. On univariable analysis, overall mortality was statistically similar between groups (MHCA/ACP 3.4% vs DHCA/RCP 2.3%, P = 0.47), but permanent neurologic deficits were significantly lower in the DHCA/RCP cohort (MHCA/ACP 3.9% vs DHCA/RCP 1.0%, P = 0.02). Multivariable analysis showed no difference in mortality nor perioperative stroke between perfusion cohorts. CONCLUSIONS: Both MHCA/ACP and DHCA/RCP are excellent neuroprotective strategies that produce low mortality in patients undergoing elective HEMI. DHCA/RCP may demonstrate theoretically improved neurologic outcomes compared with MHCA/ACP, but this topic warrants further study.

Evaluating the translation of implementation science to clinical artificial intelligence: a bibliometric study of qualitative research.

Introduction: Whilst a theoretical basis for implementation research is seen as advantageous, there is little clarity over if and how the application of theories, models or frameworks (TMF) impact implementation outcomes. Clinical artificial intelligence (AI) continues to receive multi-stakeholder interest and investment, yet a significant implementation gap remains. This bibliometric study aims to measure and characterize TMF application in qualitative clinical AI research to identify opportunities to improve research practice and its impact on clinical AI implementation. Methods: Qualitative research of stakeholder perspectives on clinical AI published between January 2014 and October 2022 was systematically identified. Eligible studies were characterized by their publication type, clinical and geographical context, type of clinical AI studied, data collection method, participants and application of any TMF. Each TMF applied by eligible studies, its justification and mode of application was characterized. Results: Of 202 eligible studies, 70 (34.7%) applied a TMF. There was an 8-fold increase in the number of publications between 2014 and 2022 but no significant increase in the proportion applying TMFs. Of the 50 TMFs applied, 40 (80%) were only applied once, with the Technology Acceptance Model applied most frequently (n = 9). Seven TMFs were novel contributions embedded within an eligible study. A minority of studies justified TMF application (n = 51,58.6%) and it was uncommon to discuss an alternative TMF or the limitations of the one selected (n = 11,12.6%). The most common way in which a TMF was applied in eligible studies was data analysis (n = 44,50.6%). Implementation guidelines or tools were explicitly referenced by 2 reports (1.0%). Conclusion: TMFs have not been commonly applied in qualitative research of clinical AI. When TMFs have been applied there has been (i) little consensus on TMF selection (ii) limited description of selection rationale and (iii) lack of clarity over how TMFs inform research. We consider this to represent an opportunity to improve implementation science's translation to clinical AI research and clinical AI into practice by promoting the rigor and frequency of TMF application. We recommend that the finite resources of the implementation science community are diverted toward increasing accessibility and engagement with theory informed practices. The considered application of theories, models and frameworks (TMF) are thought to contribute to the impact of implementation science on the translation of innovations into real-world care. The frequency and nature of TMF use are yet to be described within digital health innovations, including the prominent field of clinical AI. A well-known implementation gap, coined as the "AI chasm" continues to limit the impact of clinical AI on real-world care. From this bibliometric study of the frequency and quality of TMF use within qualitative clinical AI research, we found that TMFs are usually not applied, their selection is highly varied between studies and there is not often a convincing rationale for their selection. Promoting the rigor and frequency of TMF use appears to present an opportunity to improve the translation of clinical AI into practice.

CANVAS: una nueva etiología de la ataxia del adulto. La asociación con tos orienta al diagnóstico. Comunicación de 2 pacientes

Presentamos dos pacientes no relacionados con ataxia cerebelosa de inicio tardío asociada con neuropatía y tos seca de larga data. Un paciente tenía dos hermanos afectados con neuropatía sensorial y tos. Ambos probandos tuvieron investigaciones extensas que incluyó pruebas genéticas negativas para las ataxias más comunes, así como pruebas paraneoplásicas y otras causas inmunológicas. Ambos pacientes mostraron una expansión intrónica anormal en el pentanucleótido AAGGG del gen RFC1. Esta etiología se informa como causa frecuente de ataxia de inicio en adultos; la presencia de tos puede conducir al diagnóstico correcto.

We report two unrelated patients with late-onset cerebellar ataxia associated with neuropathy and a long-standing dry cough. One patient had two siblings affected with sensory neuropathy and cough. Both probands had extensive investigations including genetics testing negative for most common ataxias as well as testing for paraneoplasic and other immunologic causes. Both patients showed an abnormal intronic expansion in the pentanucleotide AAGGG of the gene RFC1. This etiology is being reported as frequent cause of adult-onset ataxia; the presence of cough may lead to the correct diagnosis.

Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

Long-term outcomes of aortic root operations in the United States among Medicare beneficiaries.

OBJECTIVE: The best method of aortic root repair in older patients remains unknown given a lack of comparative effectiveness of long-term outcomes data. The objective of this study was to compare long-term outcomes of different surgical approaches for aortic root repair in Medicare patients using The Society of Thoracic Surgeons Adult Cardiac Surgery Database-Centers for Medicare & Medicaid Services-linked data. METHODS: A retrospective cohort study was performed by querying the Society of Thoracic Surgeons Adult Cardiac Surgery Database for patients aged 65 years or more who underwent elective aortic root repair with or without aortic valve replacement. Primary long-term end points were mortality, any stroke, and aortic valve reintervention. Short-term outcomes and long-term survival were compared among each root repair strategy. Additional risk factors for mortality after aortic root repair were assessed with a multivariable Cox proportional hazards model. RESULTS: A total of 4173 patients aged 65 years or more underwent elective aortic root repair. Patients were stratified by operative strategy: mechanical Bentall, stented bioprosthetic Bentall, stentless bioprosthetic Bentall, or valve-sparing root replacement. Mean follow-up was 5.0 (±4.6) years. Relative to mechanical Bentall, stented bioprosthetic Bentall (adjusted hazard ratio, 0.80; confidence interval, 0.66-0.97) and stentless bioprosthetic Bentall (adjusted hazard ratio, 0.70; confidence interval, 0.59-0.84) were associated with better long-term survival. In addition, stentless bioprosthetic Bentall (adjusted hazard ratio, 0.64; confidence interval, 0.47-0.80) and valve-sparing root replacement (adjusted hazard ratio, 0.51; confidence interval, 0.29-0.90) were associated with lower long-term risk of stroke. Aortic valve reintervention risk was 2-fold higher after valve-sparing root replacement compared with other operative strategies. CONCLUSIONS: In the Medicare population, there was poorer late survival and greater late stroke risk for patients undergoing mechanical Bentall and a higher rate of reintervention for valve-sparing root replacement. Bioprosthetic Bentall may be the procedure of choice in older patients undergoing aortic root repair, particularly in the era of transcatheter aortic valve replacement.

Tailored approach and outcomes of aortic arch reconstruction after acute type A dissection repair.

OBJECTIVE: After limited root/ascending with or without hemiarch repair for acute type A aortic dissection (ATAAD), 20% to 30% of patients require distal reintervention, frequently for arch pathology. In this report, we describe an institutional algorithm for arch management after previous limited ATAAD repair and detail operative and long-term outcomes. METHODS: From August 2005 to April 2021, 71 patients status post previous limited ATAAD repair underwent reoperative arch repair involving zones 1 to 3 for aneurysmal degeneration of residual arch dissection including complete cervical debranching with zone 0/1 thoracic endovascular aortic repair in 6 (8%), open total arch in 13 (18%), type I hybrid arch repair in 23 (32%), and type II/III hybrid arch repair in 29 (41%). RESULTS: Mean age was 59 ± 12 years; time from index ATAAD repair to reoperation was 4 (interquartile range, 2-9) years. There were 2 (2.8%) in-hospital deaths and 2 (2.8%) postdischarge deaths within 30 days of surgery. Three patients suffered stroke (4.2%) and 2 (2.8%) had acute renal failure requiring dialysis. Overall Kaplan-Meier survival was 78%, 70%, and 58% at 1, 3, and 5 years, respectively. Institutional experience appeared to play a significant role in early and late outcomes, because there have been no operative mortalities in the past 9 years and improved survival of 87% versus 66%, 79% versus 58%, and 79% versus 40% at 1, 3, and 5 years in comparisons of the past 9 years with the previous era (P = .01). CONCLUSIONS: Aneurysmal degeneration of residual arch dissection after limited ATAAD repair presents a complex reoperative challenge. An algorithmic operative approach tailored to patient anatomy and comorbidities yields excellent early and late outcomes, which continue to improve with increasing institutional experience.