Background: Janus kinase inhibitors (JAKis) are an integral aspect of the management of myeloproliferative neoplasms (MPNs). Part of the clinical benefit derived from JAKis may be due to reductions in thrombosis, a potentially life‐threatening complication of MPNs. However, evidence has emerged of adverse cardiovascular effects secondary to JAKis. We conducted a first‐of‐a‐kind meta‐analysis of the cardiovascular safety of JAKis in the treatment of MPNs.Methods: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA). Systematic searches for studies comparing JAKi treatment to a control group were conducted. Studies reporting hypertension, major adverse cardiovascular events (MACE) and thromboembolic events were included in a meta‐analysis using a random‐effects model for the primary analysis, and fixed‐effects model for any subgroup analyses performed.Results: A total of 23 publications, consisting of nine clinical trials and one retrospective analysis, met the inclusion criteria. This resulted in a pooled population of 2198 patients (JAKi n = 1145, Control n = 1053). In studies reporting thromboembolic events (n = 9), pooled analysis revealed a significantly lower rate of thromboembolic events in the JAKi group (incidence rate ratio (IRR): 0.52, 95% CI: 0.28–0.98, p = 0.04). This was primarily driven by ruxolitinib studies in myelofibrosis (MF) and polycythemia vera (PV) as when a subgroup analysis of these trials was performed (n = 7), an even more significant reduction in thromboembolic events with JAKi treatment was found (IRR: 0.41, 95%CI: 0.26–0.64, p < 0.001). There was no significant difference in MACE or hypertension between JAKi and control groups.Conclusion: This meta‐analysis suggests that JAKi treatment of MPN was associated with a reduced risk of thromboembolic events; primarily driven by studies of ruxolitinib in PV and MF. Further prospective clinical trials are warranted to confirm these findings and characterise the cardiovascular profile of other JAKis and other types of MPNs.

Background/Objectives: Sex-related differences in the presentation and outcomes of patients with mitral regurgitation (MR) undergoing mitral valve (MV) surgery remain unclear. We aimed to identify these differences to inform personalized management. Methods: A total of 143 consecutive patients undergoing surgery for MR between 2017 and 2018 were stratified by sex and assessed for differences in characteristics. We performed 1:1 propensity score matching (PSM) by sex, with baseline characteristics as covariates, yielding 38 comparable pairs which were analyzed for differences in all-cause mortality and post-operative length of stay (LOS). Results: Females (n = 67) were more symptomatic (NYHA Class ≥ 3: 73% vs. 45%, p < 0.001), had higher logistic EuroSCORE (5.5 vs. 3.9, p = 0.006), had more urgent operations (25% vs. 11%, p = 0.020), MV replacements (28% vs. 11%, p = 0.007), and secondary MR (43% vs. 16%, p < 0.001). Females had significantly smaller end-diastolic and end-systolic left ventricular (LV) diameters, though indexed diameters showed no significant differences. After PSM, females had significantly longer LOS (7 days vs. 9 days, p = 0.033) and no differences in long-term mortality (hazard ratio [HR]: 1.25, 95% confidence interval [CI]: 0.34–4.76, p = 0.7, median follow-up: 6.67 years). An indexed LV end-systolic diameter (LVESDi) > 19 mm/m² yielded greater specificity (46.0% vs. 26.7%) and comparable sensitivity (69.4% vs. 69.2%) to LVESD > 40 mm. In subgroup analyses, female patients undergoing concomitant tricuspid intervention (HR: 6.80 [1.63–37.92], p < 0.01) or urgent operation (HR: 4.85 [1.08–21.06], p = 0.04) had worse prognoses than males. Conclusions: Females undergoing MV surgery for MR had more symptoms, higher surgical risk, and longer LOS, but similar mortality compared to males. However, concomitant tricuspid intervention and urgent operations were associated with higher mortality. Our results add to the growing body of evidence that current non-indexed LV diameter thresholds may not adequately account for sex differences.

Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy’s Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients.

Background: Invasive pressure–volume loop (PVL) analysis is the gold standard method to quantify myocardial physiology. To enhance broader clinical applicability, non-invasive approaches to derive left ventricular (LV) PVLs have gained prominence, typically estimating LV end-systolic pressure (ESP) from brachial blood pressure (BP) alone. However, this approach does not account for factors that may modulate the pressure waveform as it propagates from the LV to the brachial artery, notably arterial stiffness. We trained an artificial-intelligence (AI) model to predict invasive LVESP from a set of non-invasive hemodynamic parameters and compared its performance with commonly used equations for estimating LVESP using solely brachial BPs. Methods: An in silico cohort of healthy adults ( N = 3,837, age: 48.6 ± 17.0y), previously shown to have good agreement for aortic and brachial BP with in vivo data, was split into training and validation cohorts using an internal hold-out validation approach. Clinically relevant parameters were selected as inputs to a random forest machine learning model. Results: The best performing model included systolic and diastolic brachial BP, heart rate, age, and carotid-femoral pulse wave velocity (PWV), and reliably predicted LVESP (root mean square error: 0.99 mmHg). AI-derived LVESP correlated more strongly with simulated invasive LVESP (r = 0.994) than commonly used equations (r = 0.909–0.908). Bland–Altman analysis demonstrated significant bias in brachial BP-only equations (mean bias: -4.01, limits of agreement [LoA] [± 1.96 standard deviations]: -11.1 to 3.06 mmHg), with the direction of bias varying across different ages. AI-derived LVESP displayed smaller bias (mean bias: 0.002, LoA: -1.94 to 1.94 mmHg) and had negligible age-related bias across the lifespan. Conclusions: In this hypothesis generating study, a novel non-invasive, AI-enabled approach to LVESP quantification incorporating age, PWV and other key hemodynamic parameters alongside brachial BPs yielded smaller average error across the lifespan than commonly used brachial BP-only equations. These results warrant validation in vivo to ascertain real-world predictive performance.