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Abstract Background Clinical phenotype and prognosis of heart failure (HF) may be variable among different racial populations. Therefore, a patient-level comparison of hospitalized HF patients in two university hospitals from China and Sweden was performed. Methods and results This study was a pooled data analysis of the patients prospectively enrolled in two single-center studies in China (n = 949) and Sweden (n = 1639) from 2011 to 2015. Clinical characteristics and 6-month all-cause mortality were collected. Higher systolic blood pressure (126.1 ± 20.3 vs. 114.2 ± 15.4 mmHg, p

Abstract Background Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. Methods We included a random sample of men (n = 9998) born 1915–1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25–43, 30–43 and 35–43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. Results The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20–22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25–27.5 kg/m2, 27.5–30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12–3.55), 2.98 (95% CI 1.65–5.40) and 3.55 (95% CI 1.84–6.87), respectively. Conclusions The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

Abstract Background Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015. Methods DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. Results Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p

Abstract Background Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied. Purpose To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age. Method “The Study of Men Born in 1943” is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups. Results Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model’s discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up. Conclusion In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population. Trial registration: The study is registered at Clinical Trials.gov Identifier number: NCT03138122

Abstract Background A declining trend in mean cholesterol levels and smoking has been observed in high-income western countries during the last few decades, whereas obesity rates have increased. Simultaneously, mortality from coronary heart disease has decreased. The aim of the present study was to determine whether the trends in cardiovascular risk factors have continued in successive cohorts of middle-aged women over a period of 34 years. Methods Six population-based, cross-sectional samples of women (n = 2294) mean age: 49.8 years (range: 45–54), living in Gothenburg, Sweden, were investigated between 1980 and 2014. Results Body mass index (BMI) increased over time, with a mean BMI of 24.7 kg/m2 in 1980 to 25.7 kg/m2 in 2013–2014, corresponding to a weight gain of 4.5 kg, together with an increase in the proportion of obese individuals (BMI ≥ 30 kg/m2) from 10.4 to 16.6% (p = 0.0012). The proportion of smokers and women with hypertension decreased from 34.5 to 12.8% (p = 0.0006) and from 37.7 to 24.5% (p

Abstract Background Secondary prevention after an acute myocardial infarction (AMI) reduces morbidity and mortality, but suboptimal secondary prevention of cardiovascular disease is common. Therefore, the present study aimed to identify potential underlying factors for suboptimal secondary prevention 2 years after an AMI event. Methods Patients aged 18–85 years at the time of their index AMI and hospitalized between July 2010 and December 2011, were identified retrospectively and consecutively from hospital discharge records. All patients who agreed to participate underwent a structured interview, physical examinations and laboratory analysis 2 years after their index AMI. The secondary preventive goals included are; blood pressure

Abstract Background Percutaneous coronary intervention (PCI) are increasingly used in daily clinical practice in elderly patients with acute coronary syndrome (ACS) despite limited evidence. The purpose of this study was to assess the impact of PCI on short and long term survivals in a large cohort of elderly patients with ACS from a “real world”. Methods We enrolled 491 patients aged ≥70 years admitted to our institution with ACS from 2006 to 2012. Effect of PCI on short and long term survival was evaluated in both overall and a propensity score-matched cohort. Results The mean age of the overall cohort is 83 ± 6 years. Among them, 285 were treated with PCI, whereas 206 were not. Patients treated with PCI were younger (82 ± 5 vs. 85 ± 6), more males (67% vs. 46%), with lower heart rate (77 ± 22 vs. 84 ± 21), higher eGFR (58 ± 20 vs. 47 ± 23), and less with heart failure (29% vs. 15%) (all p

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Axial spondyloarthritis (SpA) leads to structural bone lesions in every part of the vertebral column. These lesions are only partially visualized on conventional radiographs, omitting posterior parts of the vertebral column and the thoracic spine, that may nevertheless contribute to impaired spinal mobility and function in patients with axial SpA. Methods In this prospective and blinded investigation, we assessed the distribution of structural spinal lesions using magnetic resonance imaging (MRI) of the whole spine in 55 patients with axial SpA classified according to the Assessment in Spondyloarthritis International Society (ASAS) criteria. After assessment of spinal mobility and function two blinded radiologists independently evaluated MRIs of 23 vertebral units in every patient. Non-parametric statistical methods, Spearman‘s correlation and linear regression models were used to analyze structural lesion distribution and the relationship with clinical spinal mobility and function parameters. Results In 55 patients with axial SpA (13 females, average disease duration 14.9 years) 657 ventral and 139 dorsal vertebral body structural bone lesions and, notably, 534 facet joint lesions could be visualized. The median number of lesions per patient was higher in the thoracic (8.5, range 1.0–41.0) than in the lumbar (7.5, range 0.0-27.5) and the cervical spine (3.5, range 0.0-24.5). A negative correlation was noted between the number of osteoproliferative structural bone lesions and impairment of spinal mobility and function in univariate, but not in multivariate analyses. Conclusion MRI of the whole spine revealed a high prevalence of lesions in dorsal parts of the vertebral column and in the thoracic spine in patients with axial SpA that may not be adequately visualized on conventional radiographs. These findings could further contribute to a better understanding of reduced mobility of the spine typically associated with axial SpA and assist diagnostics.

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, impacts 30% of the global population. This educational pilot focused on the role primary care providers may play in the delivery of guidelines-based metabolic dysfunction-associated steatohepatitis (MASH) care. Objective Accelerate the application of guidelines-based MASH care pathways to clinical workflows. Methods A panel of six hepatologists was convened in 2021 to develop the care pathway and the subsequent pilot occurred between 2022 – 2023. The pilot was conducted across three U.S. health systems: Boston Medical Center (Boston), Methodist Health System (Dallas), and Weill Cornell Medicine (New York). Clinicians were educated on the care pathway and completed baseline/follow-up assessments. 19 primary care clinicians participated in the educational pilot baseline assessment, nine primary care clinicians completed the two-month assessment, and 15 primary care clinicians completed the four-month assessment. The primary endpoint was to assess clinician-reported adherence to and satisfaction with the care pathway. The pilot was deemed exempt by the Western Consensus Group Institutional Review Board. Results At baseline, 38.10% (n = 8) of respondents felt they had received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and 42.86% (n = 9) had not referred any patients suspected of metabolic dysfunction-associated liver disease to hepatology within a month. At four months post-intervention, 79% (n = 15) of respondents agreed or strongly agreed they received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and there was a 25.7% increase in self-reported adherence to the institution’s referral guidelines. Barriers to care pathway adherence included burden of manually calculating fibrosis-4 scores and difficulty ordering non-invasive diagnostics. Conclusions With therapeutics anticipated to enter the market this year, health systems leadership must consider opportunities to streamline the identification, referral, and management of patients with metabolic dysfunction-associated steatohepatitis. Electronic integration of metabolic dysfunction-associated steatohepatitis care pathways may address implementation challenges.

Abstract Background Pulmonary hypertension (PH) is a frequent complication in COPD and it is associated with decreased exercise capacity and poor prognosis. We hypothesized that even in COPD patients without significant PH at rest, abnormal pulmonary hemodynamics during exercise affect exercise capacity. Methods Consecutive COPD patients with clinically indicated right heart catheterization and resting mean pulmonary arterial pressure (mPAP)

Abstract Background 18F -fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the staging and response assessment of lymphoma patients. Our aim was to explore the predictive relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with early stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD16 trial. Methods 18F-FDG PET/CT images were available for MTV and TLG analysis in 107 cases from the HD16 trial. We calculated MTV and TLG using three different threshold methods (SUV4.0, SUV41% and SUV140%L), and then performed receiver-operating-characteristic analysis to assess the predictive impact of these parameters in predicting an adequate therapy response with PET negativity after 2 cycles of chemotherapy. Results All three threshold methods analyzed for MTV and TLG calculation showed a positive correlation with the PET response after 2 cycles chemotherapy. The largest area under the curve (AUC) was observed using the fixed threshold of SUV4.0 for MTV- calculation (AUC 0.69 [95% CI 0.55–0.83]) and for TLG-calculation (AUC 0.69 [0.55–0.82]). The calculations for MTV and TLG with a relative threshold showed a lower AUC: using SUV140%L AUCs of 0.66 [0.53–0.80] for MTV and 0.67 for TLG [0.54–0.81]) were observed, while with SUV41% an AUC of 0.61 [0.45–0.76] for MTV, and an AUC 0.64 [0.49–0.80]) for TLG were seen. Conclusions MTV and TLG do have a predictive value after two cycles ABVD in early stage Hodgkin lymphoma, particularly when using the fixed threshold of SUV4.0 for MTV and TLG calculation. Trial registration ClinicalTrials.gov NCT00736320 .

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder characterized by bladder pain upon filling which severely affects quality of life. Clinical presentation can vary. Local inflammatory events typify the clinical presentation of IC/BPS patients with Hunner lesions (IC/BPS-HL). It has previously been proposed that B cells are more prevalent in HL, but understanding their exact role in this environment requires a more complete immunological profile of HL. We characterized immunological dysfunction specifically in HL using immunohistochemistry. We detected significantly more plasma cells (50× increase, p

Abstract Background Myopic maculopathy (MM) is the most serious and irreversible complication of pathologic myopia, which is a major cause of visual impairment and blindness. Clinic proposed limited number of factors related to MM. To explore additional features strongly related with MM from optic disc region, we employ a machine learning based radiomics analysis method, which could explore and quantify more hidden or imperceptible MM-related features to the naked eyes and contribute to a more comprehensive understanding of MM and therefore may assist to distinguish the high-risk population in an early stage. Methods A total of 457 eyes (313 patients) were enrolled and were divided into severe MM group and without severe MM group. Radiomics analysis was applied to depict features significantly correlated with severe MM from optic disc region. Receiver Operating Characteristic were used to evaluate these features’ performance of classifying severe MM. Results Eight new MM-related image features were discovered from the optic disc region, which described the shapes, textural patterns and intensity distributions of optic disc region. Compared with clinically reported MM-related features, these newly discovered features exhibited better abilities on severe MM classification. And the mean values of most features were markedly changed between patients with peripapillary diffuse chorioretinal atrophy (PDCA) and macular diffuse chorioretinal atrophy (MDCA). Conclusions Machine learning and radiomics method are useful tools for mining more MM-related features from the optic disc region, by which complex or even hidden MM-related features can be discovered and decoded. In this paper, eight new MM-related image features were found, which would be useful for further quantitative study of MM-progression. As a nontrivial byproduct, marked changes between PDCA and MDCA was discovered by both new image features and clinic features.

Abstract Background Three-dimensional (3D) models have the unique ability to replicate individualized cardiac anatomy and may therefore provide clinical benefit. Transcatheter aortic valve implantation (TAVI) currently relies on preoperative imaging for accurate valve sizing, type of valve used, and avoidance of complications. Three-dimensional (3D) modelling may provide benefit for optimal preoperative TAVI planning. The goal of this study is to assess the utility of 3D modelling in the prediction of paravalvular leak (PVL) post TAVI. Methods Retrospective analysis of five patients who underwent TAVI at our center. Pre-operative cardiac gated CT images were utilized to create a 3D printed model with true size aortic root dimensions, including the coronary artery ostium location and left ventricular outflow tract. Deployment of the corresponding model and size TAVI valve into the created 3D model at a similar depth of implantation via fluoroscopy was performed for each patient. Degree of PVL was assessed using a closed system with water infusion under pressure over a duration of 5 s. Correlation was made between the volume obtained in the closed loop model during the pressurized period and the degree of PVL reported on the patients post TAVI placement on transthoracic echocardiogram. Results One female, and four males (age in years ranged from 68 to 87) underwent successful TAVI (0% 30-day mortality). PVL on post procedure TTE ranged from none to trivial. Successful deployment of TAVI valves inside the 3D model occurred in all cases. The average volume of water collected on three trials over 5 s ranged between 19.1–24.1 ml A multivariate linear regression showed significant association between the degree of PVL reported on post-operative transthoracic echocardiogram and the amount of volume detected in the 3D model (difference: -3.9657, 95% CI: (− 4.6761,-3.2554), p

Abstract Background To investigate the effect of asthma rehabilitation at high altitude (3100 m, HA) compared to low altitude (760 m, LA). Methods For this randomized parallel-group trial insufficiently controlled asthmatics (Asthma Control Questionnaire (ACQ) > 0.75) were randomly assigned to 3-week in-hospital rehabilitation comprising education, physical-&breathing-exercises at LA or HA. Co-primary outcomes assessed at 760 m were between group changes in peak expiratory flow (PEF)-variability, and ACQ) from baseline to end-rehabilitation and 3 months thereafter. Results 50 asthmatics were randomized [median (quartiles) LA: ACQ 2.7(1.7;3.2), PEF-variability 19%(14;33); HA: ACQ 2.0(1.6;3.0), PEF-variability 17%(12;32)]. The LA-group improved PEF-variability by median(95%CI) -7%(− 14 to 0, p = 0.033), ACQ − 1.4(− 2.2 to − 0.9, p

Abstract Background Dendritic cells (DC) induce adaptive responses against foreign antigens, and play an essential role in maintaining peripheral tolerance to self-antigens. Therefore they are involved in preventing fatal autoimmunity. Selective delivery of antigens to immature DC via the endocytic DEC-205 receptor on their surface promotes antigen-specific T cell tolerance, both by recessive and dominant mechanisms. We provide evidence that the induction of antigen-specific T cell tolerance is not a unique property of CD11c+CD8+DEC-205+ DCs. Methods We employed a fusion between αDCIR2 antibodies and the highly encephalitogenic peptide 139–151 of myelin-derived proteolipid protein (PLP139–151), to target CD11c +CD8- DCs with a DEC-205−DCIR2+ phenotype in vivo, and to substantially improve clinical symptoms in the PLP139–151-induced model of experimental autoimmune encephalomyelitis (EAE). Results Consistent with previous studies targeting other cell surface receptors, EAE protection mediated by αDCIR2-PLP139–151 fusion antibody (Ab) depended on an immature state of targeted DCIR2+ DCs. The mechanism of αDCIR2-PLP139–151 mAb function included the deletion of IL-17- and IFN-γ-producing pathogenic T cells, as well as the enhancement of regulatory T (Treg) cell activity. In contrast to the effect of αDEC-205+ fusion antibodies, which involves extrathymic induction of a Foxp3+ Treg cell phenotype in naïve CD4+Foxp3- T cells, treatment of animals with DCIR2+ fusion antibodies resulted in antigen-specific activation and proliferative expansion of natural Foxp3+ Treg cells. Conclusions These results suggest that multiple mechanisms can lead to the expansion of the Treg population, depending on the DC subset and receptor targeted.

Abstract Background The vision of transforming health systems into learning health systems (LHSs) that rapidly and continuously transform knowledge into improved health outcomes at lower cost is generating increased interest in government agencies, health organizations, and health research communities. While existing initiatives demonstrate that different approaches can succeed in making the LHS vision a reality, they are too varied in their goals, focus, and scale to be reproduced without undue effort. Indeed, the structures necessary to effectively design and implement LHSs on a larger scale are lacking. In this paper, we propose the use of architectural frameworks to develop LHSs that adhere to a recognized vision while being adapted to their specific organizational context. Architectural frameworks are high-level descriptions of an organization as a system; they capture the structure of its main components at varied levels, the interrelationships among these components, and the principles that guide their evolution. Because these frameworks support the analysis of LHSs and allow their outcomes to be simulated, they act as pre-implementation decision-support tools that identify potential barriers and enablers of system development. They thus increase the chances of successful LHS deployment. Discussion We present an architectural framework for LHSs that incorporates five dimensions—goals, scientific, social, technical, and ethical—commonly found in the LHS literature. The proposed architectural framework is comprised of six decision layers that model these dimensions. The performance layer models goals, the scientific layer models the scientific dimension, the organizational layer models the social dimension, the data layer and information technology layer model the technical dimension, and the ethics and security layer models the ethical dimension. We describe the types of decisions that must be made within each layer and identify methods to support decision-making. Conclusion In this paper, we outline a high-level architectural framework grounded in conceptual and empirical LHS literature. Applying this architectural framework can guide the development and implementation of new LHSs and the evolution of existing ones, as it allows for clear and critical understanding of the types of decisions that underlie LHS operations. Further research is required to assess and refine its generalizability and methods.

An amendment to this paper has been published and can be accessed via the original article.