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IntroductionThe cardiovascular (circulatory) system is a closed-loop system. The dynamic interaction of the heart and vascular system plays a pivotal role in maintaining adequate cardiac output. Heart failure (HF) is commonly described as a problem of the pump, that is, mechanical myocardial failure causing poor perfusion to the body. Still, the contribution of the vasculature is often neglected. Acute decompensated heart failure (ADHF) carries a poor prognosis and is often accompanied by concomitant chronic kidney disease (CKD) and acute kidney injury (AKI), which inevitably lead to adverse outcomes. The interaction of the heart with the vasculature is conceptualised as ventricular–vascular (arterial) coupling. Arterial stiffness, a non-traditional risk factor for cardiovascular disease, can be measured non-invasively using carotid–femoral pulse wave velocity (cf-PWV). High cf-PWV values mimicking increased arterial stiffness could be a causational factor towards precipitating ADHF or AKI. This study aims to assess whether cf-PWV is higher during the hospitalisation phase of patients with HF (ADHF) and CKD (AKI in CKD) compared with stable compensated HF and stable CKD.Methods and analysisThis prospective non-randomised observational study aims to recruit 120 patients aged≥60 years. Arterial stiffness will be assessed in three groups. These groups are decompensated HF with reduced ejection fraction (n=40), decompensated HF with preserved ejection fraction (n=40) and AKI in CKD stage 3a, 3b and 4, n=40. After 4 weeks from hospital discharge, patients in a stable, compensated state will be asked to attend a follow-up clinic visit to repeat the cf-PWV measurement. The primary outcome measure is variation in cf-PWV during hospitalisation against follow-up.Ethics and disseminationEthical approval was granted in October 2021 (REC reference 21/EM/0239), recruitment started in February 2022 and the results are expected in late 2025. The findings will be published in peer-reviewed journals.Trial registration numberNCT05012722.

Cardiorenal syndrome (CRS) is a challenging condition characterised by interdependent dysfunction of the heart and kidneys. Despite advancements in understanding its pathophysiology, clinical management remains complex due to overlapping mechanisms and high rates of diuretic resistance. Relevant literature was identified through a comprehensive narrative review of PubMed, Embase, and Cochrane Library databases, focusing on pivotal trials relating to CRS from 2005 to 2024. This review aims to provide a pragmatic, evidence-based approach to acute CRS management by addressing common misconceptions, outlining diagnostic strategies, and proposing a structured algorithm to manage diuretic resistance. We discuss the role of thoracic and venous excess ultrasound (VeXUS) in providing reliable measures of systemic congestion, natriuresis-guided sequential nephron blockade, and more targeted therapies, including ultrafiltration in refractory cases. In addition, we explore emerging trials that target renal hypoperfusion and venous congestion in CRS. Designed for a broad audience, including general physicians, cardiologists, and nephrologists, this review integrates clinical evidence with practical guidance to support effective and timely decision-making in the care of patients with CRS.

BackgroundCardiorenal syndrome (CRS) is an umbrella term for disorders involving both the heart and kidneys in which acute or chronic dysfunction in one organ may induce dysfunction in the other. Diuretics are one of the mainstay treatments of CRS, however at present there are no current guidelines for CRS and there is often hesitancy to prescribe diuretics due to fears of worsening kidney function.AimThis review aims to identify if use of diuretics in CRS reduces all-cause mortality. Secondary objectives include assessing if diuretics reduce hospitalisations, preserve renal function, or increase serious adverse events.MethodsOnly studies with CRS patients treated with diuretics with a minimum population of 50 were included. A systematic search with specific terms including ‘CRS’’, ‘Diuretics’, ‘Heart failure’ was conducted via Medline, Embase and Cochrane databases. Over 1622 studies were identified. After screening and full text analysis, 12 studies were included within this review.ResultsDiuretics were found to be safe and effective if dosed appropriately. Loop diuretics at high doses were found to increase renal decline and risk of hospitalisation in one study. However, the mineralocorticoid receptor antagonists and finerenone, when dosed appropriately, were found to significantly reduce all-cause mortality and hospitalisation across 7 studies. Finerenone did not show an increased incidence of renal decline with use, and in one study significantly reduced renal decline in CRS.ConclusionDiuretics are a safe and effective option in the management of CRS if managed appropriately with close monitoring. Currently diuretics are one of the mainstays of treatments within CRS and will remain so, as alternative therapies such as ultrafiltration have not been shown to be as effective and with more adverse events. There is scope for further research such as diuretics in combination with sodium glucose co-transporter 2 inhibitors which has shown promising outcomes.

Background Chronic rejection is the single biggest cause of premature kidney graft failure. HLA antibodies (Ab) are an established prognostic biomarker for premature graft failure so there is a need to test whether treatment decisions based on the presence of the biomarker can alter prognosis. The Optimised TacrolimuS and MMF for HLA Antibodies after Renal Transplantation (OuTSMART) trial combines two elements. Firstly, testing whether a routine screening programme for HLA Ab in all kidney transplant recipients is useful by comparing blinding versus unblinding of HLA Ab status. Secondly, for those found to be HLA Ab+, testing whether the introduction of a standard optimisation treatment protocol can reduce graft failure rates. Methods OuTSMART is a prospective, open-labelled, randomised biomarker-based strategy (hybrid) trial, with two arms stratified by biomarker (HLA Ab) status. The primary outcome was amended from graft failure rates at 3 years to time to graft failure to increase power and require fewer participants to be recruited. Length of follow-up subsequently is variable, with all participants followed up for at least 43 months up to a maximum of 89 months. The primary outcome will be analysed using Cox regression adjusting for stratification factors. Analyses will be according to the intention-to-treat using all participants as randomised. Outcomes will be analysed comparing standard care versus biomarker-led care groups within the HLA Ab+ participants (including those who become HLA Ab+ through re-screening) as well as between HLA-Ab-unblinded and HLA-Ab-blinded groups using all participants. Discussion Changes to the primary outcome permit recruitment of fewer participants to achieve the same statistical power. Pre-stating the statistical analysis plan guards against changes to the analysis methods at the point of analysis that might otherwise introduce bias through knowledge of the data. Any deviations from the analysis plan will be justified in the final report. Trial registration ISRCTN registry, ID: ISRCTN46157828 . Registered on 26 March 2013; EudraCT 2012–004308-36 . Registered on 10 December 2012.

BackgroundElevated arterial stiffness can contribute to cardiac and renal dysfunction. In heart failure with preserved ejection fraction (HFpEF), increased arterial afterload may drive disease progression through ventricular-arterial decoupling— distinguishing it from HF with reduced ejection fraction (HFrEF) which primarily stems from intrinsic myocardial disease. In the kidneys, this can impose excessive mechanical stress on glomerular cells and disrupt perfusion. Carotid-femoral pulse wave velocity (cf-PWV, normal <10m/s) is the gold-standard measure of arterial stiffness. This study evaluated cf-PWV differences between HFrEF, HFpEF and acute-on-chronic kidney disease (AKI on CKD) in decompensated and compensated states to elucidate the dynamic interplay between arterial stiffness and clinical stability.MethodsThis single-centre prospective study recruited 109 patients aged ≥60-years (from an initial 120, with 11 exclusions). Each participant underwent comprehensive assessment during hospitalisation (decompensated state) and at follow-up (compensated state), including blood tests, ECG, cf-PWV measurement using the SphygmoCor® tonometry device on the carotid and femoral arteries (figure 1). Echocardiogram was performed if unavailable within 12 months. Statistical analysis used paired t-test, Chi-square test and repeated measures ANOVA to assess changes in PWV from decompensation to discharge, adjusting for covariates.ResultsBaseline characteristics are summarised in table 1. There were no significant differences in age, sex, body mass index and ethnicity. Cf-PWV differed significantly between groups (p=0.013), with HFpEF demonstrating the highest average PWV (13.9±4.4m/s, followed by AKI on CKD (11.7±3.7m/s) and HFrEF (10.9± 4.9m/s). All groups exhibited elevated PWV (>10m/s) during decompensation, with significant reductions observed in the compensated state for HFpEF (to 10.8±2.8m/s, p<0.001) and AKI on CKD (to 10.8±3.4m/s, p=0.04). Even in the compensated state, mean PWV remained >10m/s, unlike HFrEF which dropped below this threshold (9.8±3.1m/s). After adjusting for all cardiovascular medications, changes in weight, natriuretic peptides and systolic blood pressure on repeated measures ANOVA, the change in PWV over time was significant across all groups (p=0.011) and differed significantly between the groups (p=0.021).ConclusionArterial stiffness plays a key role in the pathogenesis of decompensation in HFpEF and AKI on CKD. Despite clinical recovery, PWV remained elevated, reinforcing arterial stiffness as a chronic pathological driver in HFpEF and CKD. This suggests its contribution to both acute decompensation and sustained vascular dysfunction, predisposing patients to future instability. While our findings highlight the potential utility of PWV measurement in identifying patients at higher risk of decompensation—particularly in HFpEF—larger studies are needed to validate its role in risk stratification and clinical utility.Abstract 5-015 Table 1Comparison of baseline characteristics between the 3 groups HFrEF (n=37) HFpEF (n=36) AKI on CKD (n=36) p value Age – mean ± SD 75.4 ± 8.7 77.0 ± 7.5 75.6 ± 8.6 0.654 Female sex – n (%) 10 (27) 16 (44) 14 (39) 0.287 BMI – mean ± SD 29.6 ± 7.1 29.8 ± 6.8 27.6 ± 8.1 0.390 Ethnicity – n (%) Asian Black White Other 4 (11)3 (8)27 (73)3 (8) 2 (6)1 (3)30 (83)3 (8) 4 (11)2 (6)28 (77)2 (6) 0.837 Medical history – n (%) Atrial fibrillation Diabetes mellitus Hypertension IHD High cholesterol Valvular HD Stroke/ TIA Asthma/COPD 25 (68)12 (32)20 (54)14 (38)9 (24)5 (14)7 (19)10 (27) 24 (67)19 (53)23 (64)13 (36)9 (25)9 (25)5 (14)8 (22) 16 (45.7)18 (50)26 (72)12 (33)10 (28)05 (14)7 (19) 0.2790.1600.2720.4460.8850.0060.7440.591 NYHA Class – n (%) I II III IV 03 (8)18 (49)16 (43) 03 (8)12 (33)20 (56) N/A -- Medications – n (%) ACE inhibitors ARBs ARNI Amiodarone Beta-blockers Digoxin DHP CCB Non-DHP CCB Hydralazine Loop diuretics MRA Nitrates Statins SGLT2 inhibitors 6 (16)2 (5)23 (62)7 (19)34 (92)8 (22)2 (5)01 (3)34 (92)20 (54)016 (43)24 (65) 8 (22)2 (6)1 (3)1 (3)32 (89)7 (19)9 (25)1 (3)5 (14)32 (89)9 (25)4 (11)22 (61)13 (36) 10 (28)4 (11)01 (3)17 (47)1 (3)8 (22)1 (3)3 (8)19 (53)1 (3)2 (6)23 (64)9 (25) 0.4910.570<0.0010.015<0.0010.0460.1300.1300.222<0.001<0.0010.1150.1550.002 Biochemistry NT-proBNP- mean ± SD 1150.8 ± 858.9 792.8 ± 867.8 629.5 ± 753.2 0.027 Estimated GFR 51.3 ± 21.3 52.7 ± 22.0 38.6 ± 22.2 0.013 White cell count (x109/L) 8.2 ± 2.7 8.4 ± 4.0 10.9 ± 5.1 0.009 Haemoglobin 130 ± 16.7 120.5 ± 21.4 117.5 ± 22.8 0.027 Platelets – median (IQR) 210 (91.5) 231 (151.5) 243 (114) 0.409 Echocardiogram LVEF (%) 30.5 ± 11.5 54.5 ± 5.6 50.2 ± 10.5 - LVEDD (mm) 55.6 ± 10.8 47 ± 6.4 49.3 ± 5.3 <0.001 Indexed LV mass 125.0 ± 57.2 103.0 ± 32.8 91.4 ± 23.0 0.002 Average E/e’ – median (IQR) 13.0 (6.2) 15.7 (7.2) 11.7 (4.3) 0.033 TAPSE 16.3 ± 13.4 15.8 ± 5.4 15.9 ± 3.8 0.963 Haemodynamics Peripheral systolic BP 111.9 ± 14.9 121.5 ± 16.8 129.4 ± 23.4 <0.001 Peripheral diastolic BP 67.7 ± 9.4 68.2 ± 9.2 71.2 ± 9.8 0.227 Pulse wave velocity (m/s) 10.9 ± 4.9 13.9 ± 4.4 11.7 ± 3.7 0.013 Abbreviations: ACEi- angiotensin converting enzyme inhibitor; ARB- angiotensin receptor blocker; BMI- body mass index; BNP- B-type natriuretic peptide; CKD- chronic kidney disease; COPD- chronic obstructive pulmonary disease; (N)-DHP CCB- (non)-dihydropyridine calcium channel blockers; GFR- glomerular filtration rate; LVEDD- left ventricular end-diastolic diameter; LVEF- left ventricular ejection fraction; MRA- mineralocorticoid receptor antagonists; SGLT2i- sodium glucose co-transporter 2 inhibitor; TAPSE- tricuspid annular planar systolic exercise; TIA- transient ischaemic attackAbstract 5-015 Figure 1Comparison of pulse wave velocity at decompensated and compensated states in HFrEF, HFpEF and acute on chronic kidney disease[Image Omitted. See PDF.]

IntroductionDespite the recent inclusion of advanced chronic kidney disease (CKD) in modern heart failure (HF) trials such as DAPA-CKD, cardiorenal syndrome (CRS) remains an undertreated disorder with a paucity of evidence-based therapies. Cardiorenal clinics (CRC) have emerged as a collaborative initiative between cardiologists and nephrologists to provide a multi-disciplinary approach. To date, little data exist on the performance and outcomes of this clinic model. This study provides insight into how patient characteristics influence decisions on the choice of renal replacement therapy (RRT), and whether such decisions affect patient outcomes.MethodsThis was a single-centre retrospective study of 151 consecutive patients who were referred to the CRC from primary and secondary care between January 2016 and March 2020. Criteria for referral were patients with an estimated glomerular filtration rate ≤30 mL/min/1.73 m2 and HF, regardless of ejection fraction. CRC consisted of a consultant nephrologist and cardiologist with a specialist interest in HF. All-cause mortality and hospitalisations within 12 months from the last clinic appointment were compared between patients managed conservatively and those on RRT. Morbidity outcomes before and after RRT include changes in New York Heart Association (NYHA) class, medication burden, weight and systolic blood pressure (SBP).ResultsWithin the study cohort of 151 patients, the most common form of CRS was type 2 (i.e. chronic HF induced the onset or progression of CKD). As summarized in Table 1, 113 patients (75%) were managed conservatively, of which 59% (n=67) were treated with ACE inhibitors, angiotensin-receptor blockers or Sacubitril/Valsartan (Table 2). This group was more likely to be older with a higher prevalence of renovascular and ischaemic heart disease and Type 2 CRS. In comparison, the RRT group (n=38; 25%) had a higher prevalence of diabetic nephropathy, HF with preserved ejection fraction, and Type 4 and 5 reno-cardiac syndrome. 37% (n=14) were on haemodialysis, 21% (n=8) peritoneal dialysis and 42% (n=16) had renal transplants. 63% (n=10) of transplant recipients developed CRS from an acute coronary event or sepsis. No significant differences in all-cause mortality or hospitalisation were found (Table 1), however one confounding factor was the larger number of patients on cardiac resynchronisation therapy in the conservative group. Patients on dialysis demonstrated significant reduction in weight, SBP, medication burden and an improvement in NYHA class (Figure 1).Abstract 121 Table 1Comparison of patient characteristics and outcomes- n (%) Conservative Management (n=113) Renal replacement therapy (n=38) p value Age—mean (SD) 76 (11.3) 64.1 (13.8) <0.001 Male Gender 85 (75.2) 23 (60.5) 0.08 Hypertension 53 (46.9) 20 (52.6) 0.54 Diabetes Mellitus 48 (42.5) 23 (60.5) 0.054 Ischaemic heart disease 62 (54.9) 13 (34.2) 0.028 Stroke 7 (6.2) 1 (2.6) 0.39 Estimated GFR-- mean (SD) 31.4 (14.2) 23.8 (10.4) 0.03 Heart failure characteristics HFrEF (LVEF ≤40%) 64 (57) 16 (42.1) 0.136 HFmrEF (LVEF 41-49%) 17 (15) 3 (7.9) 0.41 HFpEF (LVEF ≥50%) 32 (28) 19 (50) 0.018 NT-proBNP—mean (SD) 840 (984) 1207 (1439) 0.145 ICD 4 (3.5) 4 (10.8) 0.096 CRT-D 23 (20.4) 1 (2.7) 0.01 CRT-P 16 (14.2) 2 (5.4) 0.143 Aetiology of CKD Diabetic nephropathy 13 (11.5) 15 (39.5) <0.001 Renovascular disease 30 (26.5) 3 (7.9) 0.016 Hypertensive nephropathy 3 (2.7) 0 1 Primary glomerulonephritis 1 (0.9) 4 (10.5) 0.004 Other 5 (4.4) 10 (26) <0.001 Unclear aetiology 61 (54) 6 (15.8) 0.012 Classification of CRS Type 1 (Acute CRS) 14 (12.4) 2 (5.3) 0.27 Type 2 (Chronic CRS) 73 (64.6) 12 (31.6) <0.001 Type 3 (Acute RCS) 0 2 (5.3) 0.094 Type 4 (Chronic RCS) 10 (8.8) 10 (26.3) 0.006 Type 5 (Secondary RCS) 11 (9.7) 11 (28.9) 0.004 Not classified 5 (4.4) 1 (2.6) 0.62 Outcomes Death 48 (42.5) 14 (36.8) 0.57 Hospitalization- median (IQR) 0 (0-2) 1 (0-2) 0.17 LOHS- median (IQR) 1 (0-5) 1.5 (0-9) 0.87 CRS= cardiorenal syndrome; GFR= glomerular filtration rate (mL/min/1.73m2); HFrEF/HFpEF= Heart failure with reduced/preserved ejection fraction; IQR= interquartile range; LOHS= length of hospital stay; RCS= reno-cardiac syndromeAbstract 121 Table 2Comparison of heart failure therapies- n (%) Conservative Management (n=113) Renal replacement therapy (n=38) p value Medications ACE inhibitors 39 (34.5) 10 (26) 0.35 Angiotensin-receptor blockers 15 (13.3) 4 (10.5) 0.66 Sacubitril/Valsartan 13 (11.5) 1 (2.6) 0.10 Beta-blockers 95 (84.1) 27 (71.1) 0.78 MRA 31 (27.4) 7 (18.4) 0.27 SGLT2-inhibitors 1 (0) 0 0.56 Device therapy ICD 4 (3.5) 4 (10.8) 0.096 CRT-D 23 (20.4) 1 (2.7) 0.01 CRT-P 16 (14.2) 2 (5.4) 0.143 CRT-D/P: cardiac resynchronisation therapy with defibrillator/pacemaker; ICD= implantable cardioverter defibrillator; MRA= mineralocorticoid receptor antagonist; SGLT2-inhibitor= Sodium-glucose 2 transporter inhibitorsAbstract 121 Figure 1ConclusionsOur study highlights specific phenotypes in CRS that are deemed more appropriate for conservative management and ones more suited for RRT. Reassuringly, RRT did not increase mortality in this high-risk cohort any more than those managed medically and so should be considered as a safe treatment, when clinically appropriate. Irrespective of treatment strategy, CRS remains a disorder with high mortality. However, RRT has been shown to improve various aspects of morbidity. The dedicated CRC enabled some patients to be optimized for bridging to renal transplant. Finally, prescriptions of guideline-directed medical therapies for HF remain under-prescribed, highlighting the need to overcome this ‘treatment-risk paradox’, whereby higher risk patients most likely to benefit are less likely to receive the recommended best medical therapy.Conflict of InterestNil

Recommender systems have become a core component of various online platforms, helping users get relevant information from the abundant digital data. Traditional RSs often generate static recommendations, which may not adapt well to changing user preferences. To address this problem, we propose a novel reinforcement learning (RL) recommendation algorithm that can give personalized recommendations by adapting to changing user preferences. However, a significant drawback of RL-based recommendation systems is that they are computationally expensive. Moreover, these systems often fail to extract local patterns residing within dataset which may result in generation of low quality recommendations. The proposed work utilizes biclustering technique to create an efficient environment for RL agents, thus, reducing computation cost and enabling the generation of dynamic recommendations. Additionally, biclustering is used to find locally associated patterns in the dataset, which further improves the efficiency of the RL agent’s learning process. The proposed work experiments eight state-of-the-art biclustering algorithms to identify the appropriate biclustering algorithm for the given recommendation task. This innovative integration of biclustering and reinforcement learning addresses key gaps in existing literature. Moreover, we introduced a novel strategy to predict item ratings within the RL framework. The validity of the proposed algorithm is evaluated on three datasets of movies domain, namely, ML100K, ML-latest-small and FilmTrust. These diverse datasets were chosen to ensure reliable examination across various scenarios. As per the dynamic nature of RL, some specific evaluation metrics like personalization, diversity, intra-list similarity and novelty are used to measure the diversity of recommendations. This investigation is motivated by the need for recommender systems that can dynamically adjust to changes in customer preferences. Results show that our proposed algorithm showed promising results when compared with existing state-of-the-art recommendation techniques.

Since globalization has increased both production and population, it has also increased environmental damage. This is why the development of renewable energy sources is crucial to the survival of humanity and the planet itself. Business patterns across the various nations, however, have changed significantly over time. This study examines how environmental taxes and renewable energy electricity affect renewable energy consumption in emerging seven economies by using panel dataset over the period of 1990 to 2020. Control variables include economic growth, carbon emissions, and environmental innovation. The results confirmed the presence of the long-run co-integration association, the existence of slope coefficient heterogeneity, and the dependency of cross sections using several panel data methods. Since the data was not normally distributed, a new technique known as method of moments quantile regression (MMQR) was applied in this study. The projected results contend that the major factors of renewable energy consumption are renewable energy output, environmental taxation, economic growth, and carbon emissions. However, eco-friendly innovations drastically cut back on the need for renewable energy. Bootstrap quantile regression verifies the results’ reliability, and the panel Granger causality test corroborates that the listed factors have a bidirectional causal relationship with renewable energy usage. Furthermore, this research recommends boosting spending on renewable electricity, the environmental tax sector, and ecological innovation in order to expand the use of renewable energy.

Background. The objectives were to assess the impact of dental caries on the daily living of the geriatric population and determine the factors that influence the relationship between dental health and the daily living of the geriatric population. Methods. A descriptive cross-sectional study was carried out over six months at Rawalpindi’s public and private dental hospitals. Participants aged≥60 years, both male and female, were selected. The calculated sample size was 281. Desired sample from one of the dental hospitals was collected using a non-probability consecutive sampling strategy. Data about sociodemographic characteristics and the DMFT index were collected. Adapted validated tool dental impact on daily living (DIDL) was used to assess the impact of dental health on daily living. Results. Chi-squared test of association showed a positive association between the DIDL and sociodemographic variables, including age (P=0.001), gender (P=0.001), education (P=0.001), income (P=0.001), occupation (P=0.029), marital status (P=0.001), living arrangement (P=0.001), and history of chronic illnesses (P=0.001). The association between the DMFT index and DIDL also showed statistically significant results (P=0.001). Binary logistic regression analysis indicated that gender (OR=6.98, P=0.005) and the individual’s dental health (OR=6.43, P=0.001) were the strongest predictors of the impact experienced in daily life activities. The overall model was statistically significant (χ2=51.24, P=0.001), and the variables were responsible for 32.4% of the variance in the outcome variable. Conclusion. The study provides strong evidence that sociodemographic factors, DMFT index, gender, and individual dental health significantly contribute to the impact of dental health on daily living. Gender and individual dental health emerge as particularly influential predictors. These findings emphasize the need for targeted interventions and awareness programs, especially for groups with a higher risk of experiencing a significant impact on daily life due to dental issues.