Search

Abstract Background To analyse the nature of medical or technical emergency issues of ambulatory peritoneal dialysis (PD) patients calling a nurse-provided emergency PD support service of a reference centre that is provided all year in the after-hours. Methods We retrospectively analysed patients’ chief complaint, urgency, resolution of and association to current PD treatment and modality directed to an on-call nurse-provided PD support service from 2015–2021 based on routinely collected health data. Calls were systematically categorized being technical/procedural-, medical-, material-related or type of correspondence. Call urgency was categorized to have “immediate consequence”, inquiry was eligible for “processing next working day” or whether there was “no need for further action”. Call outcomes were classified according to whether patients were able to initiate, resume or finalize their treatments or whether additional interventions were required. Unexpected adverse events such as patients’ acute hospitalization or need for nurses’ home visits were evaluated and quantified. Results In total 753 calls were documented. Most calls were made around 7:30 a.m. (5:00–9:00; median, 25-75th CI) and 6:30 p.m. (5:00–8:15). 645 calls were assigned to continuous ambulatory- (CAPD) or automated PD (APD). Of those, 430 calls (66.7%) had an “immediate consequence”. Of those 77% (N = 331) were technical/procedural-, 12.8% (N = 55) medical- and 6.3% (N = 27) material related issues. 4% (N = 17) were categorized as other correspondence. Issues disrupting the course of PD were identified in 413 cases. In 77.5% (N = 320) patients were able to initiate, resume or finalize their treatment after phone consultation. Last-bag exchange was used in 6.1% enabling continued therapy in 83.6%. In 35 cases a nurse visit at patients’ home or patients' visit to the practice at the earliest possible date were required, while hospitalization was required in seven medical category cases (5.4% and 1.09% of total assessed calls, respectively). Conclusion The on-call PD-nurse provides patient support for acute and imminent issues enabling them to successfully initiate, resume or finalize their prescribed treatment. Nurses triage of acute conditions facilitated rapid diagnostics and therapy. Maintaining quality PD homecare, the provision of trained personnel is indispensable. The information gathered in this study may therefore be used as a foundation to tailor educational programs for nephrology nurses and doctors to further develop their competencies in PD.

Summary: Background: Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. Methods: In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7–9 ng/ml; Standard Care arm), or an initial 7-day fixed 5 mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5–7 ng/ml; Slow & Low arm). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure, or death at 6 months with a non-inferiority margin of 12.5%. (EudraCT-Nr: 2013-001770-19. Findings: The combined primary endpoint in the Slow & Low arm was non-inferior compared to the Standard Care arm (22.1% versus 20.7%; difference: 1.4%, 90% CI −5.5% to 8.3%). The overall rate of BPAR including borderlines was similar (Slow & Low 17.4% versus Standard Care 16.6%). Safety parameters such as delayed graft function, kidney function, donor specific HLA-antibodies, infections, or post-transplantation diabetes mellitus did not differ. Interpretation: This is the first study to show that an initial fixed dose of 5 mg per day followed by lower tacrolimus exposure is non-inferior compared to standard tacrolimus therapy and equally efficient and safe within 6 months after renal transplantation. These data suggest that therapeutic drug monitoring for prolonged release tacrolimus can be abandoned until start of the second week after transplantation. Funding: Investigator-initiated trial, financial support by Astellas Pharma GmbH.

Background: Studies of cardiovascular disease risk prediction by machine learning algorithms often do not assess their ability to generalize to other populations and few of them include an analysis of the interpretability of individual predictions. This manuscript addresses the development and validation, both internal and external, of predictive models for the assessment of risks of major adverse cardiovascular events (MACE). Global and local interpretability analyses of predictions were conducted towards improving MACE's model reliability and tailoring preventive interventions. Methods: The models were trained and validated on a retrospective cohort with the use of data from Ribeirão Preto Medical School (RPMS), University of São Paulo, Brazil. Data from Beth Israel Deaconess Medical Center (BIDMC), USA, were used for external validation. A balanced sample of 6,000 MACE cases and 6,000 non-MACE cases from RPMS was created for training and internal validation and an additional one of 8,000 MACE cases and 8,000 non-MACE cases from BIDMC was employed for external validation. Eight machine learning algorithms, namely Penalized Logistic Regression, Random Forest, XGBoost, Decision Tree, Support Vector Machine, k-Nearest Neighbors, Naive Bayes, and Multi-Layer Perceptron were trained to predict a 5-year risk of major adverse cardiovascular events and their predictive performance was evaluated regarding accuracy, ROC curve (receiver operating characteristic), and AUC (area under the ROC curve). LIME and Shapley values were applied towards insights about model interpretability. Findings: Random Forest showed the best predictive performance in both internal validation (AUC = 0.871 (0.859–0.882); Accuracy = 0.794 (0.782–0.808)) and external one (AUC = 0.786 (0.778–0.792); Accuracy = 0.710 (0.704–0.717)). Compared to LIME, Shapley values suggest more consistent explanations on exploratory analysis and importance of features. Conclusions: Among the machine learning algorithms evaluated, Random Forest showed the best generalization ability, both internally and externally. Shapley values for local interpretability were more informative than LIME ones, which is in line with our exploratory analysis and global interpretation of the final model. Machine learning algorithms with good generalization and accompanied by interpretability analyses are recommended for assessments of individual risks of cardiovascular diseases and development of personalized preventive actions. [ABSTRACT FROM AUTHOR]

Abstract Background Residual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients. Methods In this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes. Results In peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (rs = − 0.58, p

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD‐induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin–angiotensin–aldosterone system inhibitors, beta‐blockers, diuretics and sodium–glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end‐diastolic/end‐systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre‐clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: In patients with stable chronic heart failure with a reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) provides limited prognostic value, especially in patients with moderately to severely reduced LVEF. Echocardiographic parameters of right ventricular function may be associated with adverse clinical events in these patients. Therefore, we analyzed 164 patients with HFrEF in a prospective single-center cohort study to evaluate whether the parameters of right ventricular function are associated with worsening heart failure (WHF) hospitalizations, cardiovascular and all-cause deaths and combined endpoints. Methods: Echocardiographic cine loops were analyzed using vendor-independent post-processing software. Multivariate Cox regression analyses were performed, which were then adjusted for clinical characteristics and left ventricular functional parameters. Results: In these models, higher tricuspid annular plane systolic excursion (TAPSE) was significantly associated with lower rates of WHF hospitalizations (HR 0.880, 95%CI 0.800–0.968, p = 0.008), a composite endpoint of WHF hospitalizations and cardiovascular death (HR 0.878, 95%CI 0.800–0.964, p = 0.006), and a composite endpoint of WHF hospitalization and all-cause death (HR 0.918, 95%CI 0.853–0.988, p = 0.023). These associations were more pronounced in patients with LVEF ≤ 35%. Conclusions: In conclusion, in patients with HFrEF, TAPSE is an independent prognosticator for adverse clinical outcomes, warranting further studies to elucidate whether incorporating TAPSE into established risk scores improves their diagnostic accuracy. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of diagnosing acute coronary syndromes (ACS) in hemodialysis (HD) patients. The study aimed to explore the changes in cardiac troponin (cTn) levels during HD with different membranes and treatment modalities. The results showed significant differences in cTn changes depending on the type of membrane used. The data suggests that high-flux HD and MCO may be more effective in reducing troponin levels compared to low-flux HD and HDF. However, further research is needed to confirm these findings and establish a diagnostic algorithm for AMI in HD patients. [Extracted from the article]

While chronic heart failure (CHF) treatment has considerably improved patient prognosis and survival, the therapeutic management of acute heart failure (AHF) has remained virtually unchanged in the last decades. This is partly due to the scarcity of pre-clinical models for the pathophysiological assessment and, consequently, the limited knowledge of molecular mechanisms involved in the different AHF phenotypes. This scientific statement outlines the different trajectories from acute to CHF originating from the interaction between aetiology, genetic and environmental factors, and comorbidities. Furthermore, we discuss the potential molecular targets capable of unveiling new therapeutic perspectives to improve the outcome of the acute phase and counteracting the evolution towards CHF. [ABSTRACT FROM AUTHOR]

Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease (1,2). However, cGMP stimulation alone is limited by counter-adaptions including PDE upregulation (3). Furthermore, although PDE5A regulates nitric-oxide-generated cGMP (4,5), nitric oxide signalling is often depressed by heart disease (6). PDEs controlling natriuretic-peptide-coupled cGMP remain uncertain. Here we show that cGMP-selective PDE9A (refs 7,8) is expressed in the mammalian heart, including humans, and is upregulated by hypertrophy and cardiac failure. PDE9A regulates natriuretic-peptide- rather than nitric-oxide-stimulated cGMP in heart myocytes and muscle, and its genetic or selective pharmacological inhibition protects against pathological responses to neurohormones, and sustained pressure-overload stress. PDE9A inhibition reverses pre-established heart disease independent of nitric oxide synthase (NOS) activity, whereas PDE5A inhibition requires active NOS. Transcription factor activation and phosphoproteome analyses of myocytes with each PDE selectively inhibited reveals substantial differential targeting, with phosphorylation changes from PDE5A inhibition being more sensitive to nOs activation. Thus, unlike PDE5A, PDE9A can regulate cGMP signalling independent of the nitric oxide pathway, and its role in stress-induced heart disease suggests potential as a therapeutic target., The PDE super-family contains 11 sub-genes conferring different cyclic nucleotide and tissue selectivity (9). PDE5A was the first cGMP-selective enzyme discovered, and has a major role in erectile and pulmonary [...]

Background: Artificial Intelligence (AI) has had an important impact on many industries as well as the field of medical diagnostics. In healthcare, AI techniques such as case-based reasoning and data driven machine learning (ML) algorithms have been used to support decision-making processes for complex tasks. This is used to assist medical professionals in making clinical decisions. A way of supporting clinicians is providing predicted prognoses of various ML models. Objectives: Training an ML model based on the data of a hospital and using it on another hospital have some challenges. Methods: In this research, we applied data analysis to discover required data filters on a hospital's EHR data for training a model for another hospital. Results: We applied experiments on real-world data of ELGA (Austrian health record system) and KAGes (a public healthcare provider of 20+ hospitals in Austria). In this scenario, we train the prediction model for ELGAauthorized health service providers using the KAGes data since we do not have access to the complete ELGA data. Conclusion: Finally, we observed that filtering the data with both feature and value selection increases the classification performance of the prediction model, which is trained for another system. [ABSTRACT FROM AUTHOR]

Yet, there was little to no notable communication between cardiology and immunology up until very recently, despite longstanding recognition of inflammatory cardiac conditions, including rheumatic heart disease and infectious myocarditis. Immunology has made it into the hearts of cardiologists. Cardiology and immunology/rheumatology are historically distinct fields. [Extracted from the article]