The power of us: breaking barriers and bridging the gap of ultrasound in rheumatology to empower a new generation.

OBJECTIVE: This study assesses musculoskeletal ultrasound (MSUS) knowledge, attitudes, and practices among young rheumatologists in Mexico, aiming to identify barriers and facilitators to its clinical use. METHODS: An online survey distributed to a network of young rheumatologists captured demographics, institutional, and personal MSUS information. Multivariable analysis identified factors associated with positive MSUS attitudes. RESULTS: Ninety-six rheumatologists (39.18% national response rate) completed the survey. Of respondents (54.2% females, median age 35.1 years), 81.2% deemed MSUS necessary in clinical rheumatology. The main barriers included limited training access (56.2%) and required training time (54.1%). Lack of scientific evidence was not a major barrier (60.4%). Positive MSUS attitudes were associated with learning from conferences (p = 0.029) and colleagues (p = 0.005), formal (p = 0.043), and in-person training (p = 0.020), MSUS use in practice (p = 0.027), and use by radiologists in their institute (p < 0.001). Interest in learning MSUS (88.5%) was significantly higher in those with positive attitudes (94.4%, p < 0.001). Elastic net analysis identified key drivers, including learning MSUS from conferences, colleagues, and in residency; using MSUS in practice; respondent-performed MSUS; and MSUS use by radiologists. Statistically significant associations were found with using MSUS for synovitis/inflammatory joint disease (OR = 1.43, 95% CI 1.00-2.05) and MSUS use by radiologists in respondent's institutes (OR = 1.70, 95% CI 1.20-2.90). CONCLUSION: Most young rheumatologists in Mexico recognize the necessity of MSUS in clinical practice. By addressing identified barriers, encouraging rheumatologist-radiologist collaboration, and establishing a regulatory body to certify rheumatologist's MSUS experience, there is an opportunity to empower them with the necessary skills for effective MSUS use, ultimately benefiting patient care.

Association of epicardial adipose tissue with early structural and functional cardiac changes in Type 2 diabetes.

BACKGROUND: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease. METHODS: Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range -190 to -90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression. RESULTS: T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82-0.99] vs 0.79 g/mL [0.75-0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm3/m2 vs. 9.4 cm3/m2, p < 0.001) in T2D and independently associated with LV mass/volume ratio (ß = 0.002, p = 0.01) and GLS (ß = -0.03, p = 0.03). CONCLUSIONS: Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D.

Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. METHODS: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. RESULTS: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. CONCLUSION: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. TRIAL REGISTRATION: NCT02590822.

Ethnic differences in cardiac structure and function assessed by MRI in healthy South Asian and White European people: A UK Biobank Study.

BACKGROUND: Echocardiographic studies indicate South Asian people have smaller ventricular volumes, lower mass and more concentric remodelling than White European people, but there are no data using cardiac MRI (CMR). We aimed to compare CMR quantified cardiac structure and function in White European and South Asian people. METHODS: Healthy White European and South Asian participants in the UK Biobank Imaging CMR sub-study were identified by excluding those with a history of cardiovascular disease, hypertension, obesity or diabetes. Ethnic groups were matched by age and sex. Cardiac volumes, mass and feature tracking strain were compared. RESULTS: 121 matched pairs (77 male/44 female, mean age 58 ± 8 years) of South Asian and White European participants were included. South Asian males and females had smaller absolute but not indexed left ventricular (LV) volumes, and smaller absolute and indexed right ventricular volumes, with lower absolute and indexed LV mass and lower LV mass:volume than White European participants. Although there were no differences in ventricular or atrial ejection fractions, LV global longitudinal strain was higher in South Asian females than White European females but not males, and global circumferential strain was higher in both male and South Asian females than White European females. Peak early diastolic strain rates were higher in South Asian versus White European males, but not different between South Asian and White European females. CONCLUSIONS: Contrary to echocardiographic studies, South Asian participants in the UK Biobank study had less concentric remodelling and higher global circumferential strain than White European subjects. These findings emphasise the importance of sex- and ethnic- specific normal ranges for cardiac volumes and function.

MuTATE-an R package for comprehensive multi-objective molecular modeling.

MOTIVATION: Comprehensive multi-omics studies have driven advances in disease modeling for effective precision medicine but pose a challenge for existing machine-learning approaches, which have limited interpretability across clinical endpoints. Automated, comprehensive disease modeling requires a machine-learning approach that can simultaneously identify disease subgroups and their defining molecular biomarkers by explaining multiple clinical endpoints. Current tools are restricted to individual endpoints or limited variable types, necessitate advanced computation skills, and require resource-intensive manual expert interpretation. RESULTS: We developed Multi-Target Automated Tree Engine (MuTATE) for automated and comprehensive molecular modeling, which enables user-friendly multi-objective decision tree construction and visualization of relationships between molecular biomarkers and patient subgroups characterized by multiple clinical endpoints. MuTATE incorporates multiple targets throughout model construction and allows for target weights, enabling construction of interpretable decision trees that provide insights into disease heterogeneity and molecular signatures. MuTATE eliminates the need for manual synthesis of multiple non-explainable models, making it highly efficient and accessible for bioinformaticians and clinicians. The flexibility and versatility of MuTATE make it applicable to a wide range of complex diseases, including cancer, where it can improve therapeutic decisions by providing comprehensive molecular insights for precision medicine. MuTATE has the potential to transform biomarker discovery and subtype identification, leading to more effective and personalized treatment strategies in precision medicine, and advancing our understanding of disease mechanisms at the molecular level. AVAILABILITY AND IMPLEMENTATION: MuTATE is freely available at GitHub (https://github.com/SarahAyton/MuTATE) under the GPLv3 license.

Contraception and intersection with HIV services in 11 high HIV burden sub-Saharan African countries: Results from the population-based HIV Impact Assessment cross-sectional studies conducted from 2015 to 2018.

OBJECTIVE: The United Nations' Sustainable Development Goal 3.7.1 addresses the importance of family planning. The objective of this paper is to provide information on family planning to policymakers to help increase access to contraceptive methods to women in sub-Saharan Africa. METHODS: We analyzed data from the Population-based HIV Impact Assessment studies conducted in 11 sub-Saharan African countries from 2015 to 2018 to assess the relationship between HIV services and family planning. Analyses were restricted to women aged 15-49 years who reported being sexually active within the past 12 months and had data on contraceptive use. RESULTS: Approximately 46.4% of participants reported using any form of contraception; 93.6% of whom used modern contraceptives. Women with a positive HIV status were more likely to use contraceptives (P < 0.0001) than HIV-negative women. Unmet need was higher among women who were confirmed to be HIV-negative in Namibia, Uganda, and Zambia than confirmed to be positive. Women aged 15-19 years used contraception less than 40% of the time. CONCLUSION: This analysis highlights crucial gaps in progress among HIV-negative and young women (aged 15-19 years). To provide access to modern contraception for all women, programs and governments need to focus on women who desire but do not have access to these family planning resources.

Impact of the Remission of Type 2 Diabetes on Cardiovascular Structure and Function, Exercise Capacity and Risk Profile: A Propensity Matched Analysis.

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D (n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls (n = 25). T2D remission was associated with a lower leptin-adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.

The Interfield Strength Agreement of Left Ventricular Strain Measurements at 1.5 T and 3 T Using Cardiac MRI Feature Tracking.

BACKGROUND: Left ventricular (LV) strain measurements can be derived using cardiac MRI from routinely acquired balanced steady-state free precession (bSSFP) cine images. PURPOSE: To compare the interfield strength agreement of global systolic strain, peak strain rates and artificial intelligence (AI) landmark-based global longitudinal shortening at 1.5 T and 3 T. STUDY TYPE: Prospective. SUBJECTS: A total of 22 healthy individuals (mean age 36 ± 12 years; 45% male) completed two cardiac MRI scans at 1.5 T and 3 T in a randomized order within 30 minutes. FIELD STRENGTH/SEQUENCE: bSSFP cine images at 1.5 T and 3 T. ASSESSMENT: Two software packages, Tissue Tracking (cvi42, Circle Cardiovascular Imaging) and QStrain (Medis Suite, Medis Medical Imaging Systems), were used to derive LV global systolic strain in the longitudinal, circumferential and radial directions and peak (systolic, early diastolic, and late diastolic) strain rates. Global longitudinal shortening and mitral annular plane systolic excursion (MAPSE) were measured using an AI deep neural network model. STATISTICAL TESTS: Comparisons between field strengths were performed using Wilcoxon signed-rank test (P value < 0.05 considered statistically significant). Agreement was determined using intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Minimal bias was seen in all strain and strain rate measurements between field strengths. Using Tissue Tracking, strain and strain rate values derived from long-axis images showed poor to fair agreement (ICC range 0.39-0.71), whereas global longitudinal shortening and MAPSE showed good agreement (ICC = 0.81 and 0.80, respectively). Measures derived from short-axis images showed good to excellent agreement (ICC range 0.78-0.91). Similar results for the agreement of strain and strain rate measurements were observed with QStrain. CONCLUSION: The interfield strength agreement of short-axis derived LV strain and strain rate measurements at 1.5 T and 3 T was better than those derived from long-axis images; however, the agreement of global longitudinal shortening and MAPSE was good. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Male partner age, viral load, and HIV infection in adolescent girls and young women: evidence from eight sub-Saharan African countries.

OBJECTIVE: We aimed to elucidate the role of partnerships with older men in the HIV epidemic among adolescent girls and young women (AGYW) aged 15-24 years in sub-Saharan Africa. DESIGN: Analysis of Population-based HIV Impact Assessments in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We examined associations between reported partner age and recent HIV infection among AGYW, incorporating male population-level HIV characteristics by age-band. Recent HIV infection was defined using the LAg avidity assay algorithm. Viremia was defined as a viral load of more than 1000 copies/ml, regardless of serostatus. Logistic regression compared recent infection in AGYW with older male partners to those reporting younger partners. Dyadic analysis examined cohabitating male partner age, HIV status, and viremia to assess associations with AGYW infection. RESULTS: Among 17 813 AGYW, increasing partner age was associated with higher odds of recent infection, peaking for partners aged 35-44 (adjusted odds ratio = 8.94, 95% confidence interval: 2.63-30.37) compared with partners aged 15-24. Population-level viremia was highest in this male age-band. Dyadic analyses of 5432 partnerships confirmed the association between partner age-band and prevalent HIV infection (male spousal age 35-44-adjusted odds ratio = 3.82, 95% confidence interval: 2.17-6.75). Most new infections were in AGYW with partners aged 25-34, as most AGYW had partners in this age-band. CONCLUSION: These results provide evidence that men aged 25-34 drive most AGYW infections, but partners over 9 years older than AGYW in the 35-44 age-band confer greater risk. Population-level infectiousness and male age group should be incorporated into identifying high-risk typologies in AGYW.

Food insecurity and the risk of HIV acquisition: findings from population-based surveys in six sub-Saharan African countries (2016-2017).

OBJECTIVE: To assess the potential bidirectional relationship between food insecurity and HIV infection in sub-Saharan Africa. DESIGN: Nationally representative HIV impact assessment household-based surveys. SETTING: Zambia, Eswatini, Lesotho, Uganda and Tanzania and Namibia. PARTICIPANTS: 112 955 survey participants aged 15-59 years with HIV and recency test results. MEASURES: Recent HIV infection (within 6 months) classified using the HIV-1 limited antigen avidity assay, in participants with an unsuppressed viral load (>1000 copies/mL) and no detectable antiretrovirals; severe food insecurity (SFI) defined as having no food in the house ≥three times in the past month. RESULTS: Overall, 10.3% of participants lived in households reporting SFI. SFI was most common in urban, woman-headed households, and in people with chronic HIV infection. Among women, SFI was associated with a twofold increase in risk of recent HIV infection (adjusted relative risk (aRR) 2.08, 95% CI 1.09 to 3.97). SFI was also associated with transactional sex (aRR 1.28, 95% CI 1.17 to 1.41), a history of forced sex (aRR 1.36, 95% CI 1.11 to 1.66) and condom-less sex with a partner of unknown or positive HIV status (aRR 1.08, 95% CI 1.02 to 1.14) in all women, and intergenerational sex (partner ≥10 years older) in women aged 15-24 years (aRR 1.23, 95% CI 1.03 to 1.46). Recent receipt of food support was protective against HIV acquisition (aRR 0.36, 95% CI 0.14 to 0.88). CONCLUSION: SFI increased risk for HIV acquisition in women by twofold. Heightened food insecurity during climactic extremes could imperil HIV epidemic control, and food support to women with SFI during these events could reduce HIV transmission.

Single vs Dual-site service reconfiguration during Covid-19 pandemic - A tertiary care centre experience in hip fractures and a Scoping review.

Aims and objectives: The Covid-19 pandemic has had an unprecedented effect on surgical practice and healthcare delivery globally. We compared the impact of the care pathways which segregate Covid-19 Positive and Negative patients into two geographically separate sites, on hip fracture patients in our high-volume trauma center in 3 distinct eras - the pre-pandemic period, against the first Covid-19 wave with dual-site service design, as well as the subsequent surge with single-site service delivery. In addition, we sought to invoke similar experiences of centres worldwide through a scoping literature review on the current evidence on "Dual site" reconfigurations in response to Covid-19 pandemic. Methods: We prospectively reviewed our hip fracture patients throughout the two peaks of the pandemic, with different service designs for each, and compared the outcomes with a historic service provision. Further, a comprehensive literature search was conducted using several databases for articles discussing Dual-site service redesign. Results: In our in-house study, there was no statistically significant difference in mortality of hip fracture patients between the 3 periods, as well as their discharge destinations. With dual-site reconfiguration, patients took longer to reach theatre. However, there was much more nosocomial transmission with single-site service, and patients stayed in the hospital longer. 24 articles pertaining to the topic were selected for the scoping review. Most studies favour dual-site service reorganization, and reported beneficial outcomes from the detached care pathways. Conclusion: It is safe to continue urgent as well as non-emergency surgery during the Covid-19 pandemic in a separate, geographically isolated site.

Epicardial adipose tissue in obesity-related cardiac dysfunction.

Obesity is associated with the development of heart failure and is a major risk factor for heart failure with preserved ejection fraction (HFpEF). Epicardial adipose tissue (EAT) is a unique visceral fat in close proximity to the heart and is of particular interest to the study of cardiac disease. Small poorly differentiated adipocytes with altered lipid:water content are associated with a proinflammatory secretome and may contribute to the pathophysiology observed in HFpEF. Multimodality imaging approaches can be used to quantify EAT volume and characterise EAT composition. Current research studies remain unclear as to the magnitude of effect that EAT plays on myocardial dysfunction and further work using multimodality imaging techniques is ongoing. Pharmacological interventions, including glucagon-like peptide 1 receptor agonists and sodium-dependent glucose linked transporter 2 inhibitors have shown promise in attenuating the deleterious metabolic and inflammatory changes seen in EAT. Clinical studies are ongoing to explore whether these therapies exert their beneficial effects by modifying this unique adipose deposit.

Multiomics subtyping for clinically prognostic cancer subtypes and personalized therapy: A systematic review and meta-analysis.

PURPOSE: Multiomics cancer subtyping is becoming increasingly popular for directing state-of-the-art therapeutics. However, these methods have never been systematically assessed for their ability to capture cancer prognosis for identified subtypes, which is essential to effectively treat patients. METHODS: We systematically searched PubMed, The Cancer Genome Atlas, and Pan-Cancer Atlas for multiomics cancer subtyping studies from 2010 through 2019. Studies comprising at least 50 patients and examining survival were included. Pooled Cox and logistic mixed-effects models were used to compare the ability of multiomics subtyping methods to identify clinically prognostic subtypes, and a structural equation model was used to examine causal paths underlying subtyping method and mortality. RESULTS: A total of 31 studies comprising 10,848 unique patients across 32 cancers were analyzed. Latent-variable subtyping was significantly associated with overall survival (adjusted hazard ratio, 2.81; 95% CI, 1.16-6.83; P = .023) and vital status (1 year adjusted odds ratio, 4.71; 95% CI, 1.34-16.49; P = .015; 5 year adjusted odds ratio, 7.69; 95% CI, 1.83-32.29; P = .005); latent-variable-identified subtypes had greater associations with mortality across models (adjusted hazard ratio, 1.19; 95% CI, 1.01-1.42; P = .050). Our structural equation model confirmed the path from subtyping method through multiomics subtype (߈ = 0.66; P = .048) on survival (߈ = 0.37; P = .008). CONCLUSION: Multiomics methods have different abilities to define clinically prognostic cancer subtypes, which should be considered before administration of personalized therapy; preliminary evidence suggests that latent-variable methods better identify clinically prognostic biomarkers and subtypes.

Identification of adolescent girls and young women for targeted HIV prevention: a new risk scoring tool in KwaZulu Natal, South Africa.

The ongoing spread of human immunodeficiency virus (HIV) has driven novel interventions, such as antiretrovirals, for pre-exposure prophylaxis. Interventions have overlooked a high-risk Sub-Saharan African population: adolescent girls and young women (AGYW), particularly those under 18. We apply the Balkus risk tool among rural South African AGYW (n = 971) in a hyper-endemic setting, identify limitations, and assess deficiencies with modern statistical techniques. We apply the "Ayton" tool, the first risk tool applicable to sub-Saharan African AGYW, and compare performance of Balkus and Ayton tools under varying conditions. The Ayton tool more effectively predicted HIV acquisition. In low and high-risk AGYW, the Ayton tool out-performed the Balkus tool, which did not distinguish between risk classes. The Ayton tool better captured HIV acquisition risk and risk heterogeneities due to its AGYW-focused design. Findings support use of the Ayton tool for AGYW and underscore the need for diverse prognostic tools considering epidemic severity, age, sex and transmission.Clinical Trial Number ClinicalTrials.gov (NCT01187979) and the South African National Clinical Trials Registry (SANCTR) (DOH-27-0812-3345).

Development of a prognostic tool exploring female adolescent risk for HIV prevention and PrEP in rural South Africa, a generalised epidemic setting.

OBJECTIVES: Adolescent females in sub-Saharan Africa bear a disproportionate burden of new HIV infections but have been excluded from prognostic research, such as developed risk calculators. This study examines whether validated risk calculators, which calculate HIV risk among sub-Saharan African women, can be modified to assess HIV risk among adolescent girls. The performance of selected risk variables from validated calculators and the literature was evaluated among adolescent females using modern advanced statistical tools. METHODS: Risk variables for the updated tool were selected from the CAPRISA 007 (CAP007) trial (2010-2012) questionnaires. An initially HIV-seronegative cohort of rural South African female high school students (n=1049) aged 14-25 years was selected. The number and characteristics of latent factors, or dimensions, underlying selected variables were assessed using exploratory factor analysis (EFA). The updated tool's effectiveness identifying trends in adolescent risk were assessed with latent class analysis (LCA). RESULTS: EFA identified two key latent factors: sexual behaviour and socioeconomic risk factors. Latent sexual behaviour risk influenced contraception use (0.883), perceived HIV risk (0.691) and pregnancy (-0.384). Latent socioeconomic risk influenced low HIV knowledge (0.371), financial dependence (0.532), prior HIV testing (-0.379) and alcohol use (-0.332). Using LCA, three underlying categories of adolescent females were identified: those with no, low and high risk of HIV (1.10%, 2.26% and 2.91% 1-year seroconversion rates, respectively). Herpes simplex virus serotype-2, condom contraception, alcohol use, pregnancy and age were significantly associated with higher risk class membership, while non-condom contraception was associated with lower risk class membership. CONCLUSIONS: Adolescent females are at unequal risk of acquiring HIV. Findings suggest the updated tool captures two main facets of adolescent characteristics and may identify differential risk. This work supports further investigation to inform development of targeted differentiated interventions and efficient prognostic tools for adolescents in high-risk settings.

Effect of Bruton's tyrosine kinase inhibitors on platelet aggregation in patients with acute myocardial infarction.

AIMS: Despite widespread use of dual antiplatelet therapy in acute myocardial infarction, there remains a residual risk of morbidity and mortality. Bruton's Tyrosine Kinase inhibitors have been found to inhibit platelet aggregation through the Glycoprotein VI collagen-mediated pathway. The Bruton's Tyrosine Kinase inhibitor, Ibrutinib is used in the management of haematological malignancies and another Bruton's Tyrosine Kinase inhibitor, ONO-4059 (also known as tirabrutinib), is in clinical development. This is an observational study to evaluate the effects of Ibrutinib and ONO-4059 on platelet aggregation after acute myocardial infarction. METHODS AND RESULTS: Twenty patients with a confirmed diagnosis of acute myocardial infarction were enrolled and blood samples obtained within 48 h of hospital admission. All patients were on dual antiplatelet therapy; aspirin plus a P2Y12 inhibitor (clopidogrel or ticagrelor). Blood samples were treated ex vivo with increasing concentrations of Ibrutinib (0, 0.5, 1, 2 µM) and ONO-4059 (0, 0.2, 0.5, 1 µM). Platelet aggregation was measured in response to collagen using a Multiplate analyser to estimate the area under the curve, with lower values indicating lower platelet aggregation. The median age was 63 years and 80% were male. The median area under the curve values for Ibrutinib concentrations 0 (control), 0.5, 1 and 2 µM were 18.5, 8 (P = 0.0004), 4.5 (P < 0.0001) and 2 (P < 0.0001) units and for ONO-4059 concentrations 0 (control), 0.2, 0.5 and1µM, median area under the curve values were 13, 12 (P = 0.7), 6.5 (P = 0.0001) and 5.5 (P = 0.0004 compared to control). CONCLUSION: The Bruton's Tyrosine Kinase inhibitors, Ibrutinib and ONO-4059, show further inhibition of platelet aggregation in blood samples from patients with acute myocardial infarction, receiving dual antiplatelet therapy in a dose dependent manner. These results provide a rationale for Bruton's Tyrosine Kinase inhibitors to be tested as a potential new antiplatelet strategy for acute myocardial infarction.

Medical student exposure to cardiothoracic surgery in the United Kingdom.

OBJECTIVES: There has been declining interest in cardiothoracic surgery amongst medical graduates. This survey examines the exposure of British medical students to cardiothoracic surgery in various settings and its relationship with students' interest in the speciality. METHODS: A questionnaire composed of 14 quantitative and qualitative items was distributed amongst 162 medical students. The survey included questions on demographics, interest in cardiothoracic surgery, mechanisms of exposure to the speciality and desire to pursue a career in cardiothoracic surgery before and after exposure. RESULTS: Amongst the surveyed students, 71.0% reported exposure to cardiothoracic surgery as part of their medical school curricula and 24.7% reported extracurricular exposure. Of the students, 46.7% reported clinical exposure. Overall, 27.1% of students reported interest in a career in cardiothoracic surgery, which was higher amongst students who had curricular (29.6%), clinical (35.5%) or extracurricular exposure (50.0%). Amongst interested students, 43.2% engaged in extracurricular cardiothoracic activities compared with 16.1% of students not interested in pursuing the speciality. Confidence in career choice after exposure increased more in interested students (20.4%) than not interested students (1.6%). Students rated exposure and mentorship as the most important factor in promoting a career in cardiothoracic surgery. CONCLUSIONS: Medical students with an interest in cardiothoracic surgery are more likely to organize independent attachments in the speciality and attend extracurricular events; however, many students might fail to identify cardiothoracic surgery as an area of interest because of the lack of exposure at medical school.