Research Consortium Research Articles

The burden of left ventricular assist device (LVAD) infections on costs, lengths of stay, antimicrobial consumption and resistance: a prospective case control approach

BackgroundCongestive heart failure has reached pandemic levels, and left-ventricular assist devices (LVAD) are increasingly used to treat refractory heart failure. Infection is a leading complication of LVADs. Despite numerous reports (most being retrospective), several knowledge gaps pertaining to the epidemiology and burden of an LVAD-associated infection (LVADi) remain. We sought to address these gaps using a prospective, case-control design.MethodsAll patients who received an LVAD from November 1, 2018 to August 31, 2023 (n = 110) were included and prospectively monitored until death. Data were extracted from clinical encounters and medical records in real-time or near real-time and imported to Excel and REDcap electronic data capture tools. An LVADi was ascertained using definitions from the mechanical circulatory support academic research consortium in conjunction with and the U.S. National Health Safety Network. All meeting those definitions were included as ‘cases.’ Patients with no LVADi were controls. Excess lengths-of-stays (LOS) and direct costs were calculated from billing records using a commercial cost accounting software platform (Strata®, Chicago, IL).ResultsThe amount of healthcare contact before implantation and discharge to a rehabilitation or skilled nursing facility instead of home were the primary risks for infection, resulting in mean excesses of 25 hospital and 60 antibiotic-days and $43,000 per event. One-third occurred > 1 year after implantation. 35% developed > 1 infection. Gram-negative, fungal, and antimicrobial-resistant organisms predominated deep or repeat infections. 7.2% developed ≥ 3 infections. Organisms became increasingly antimicrobial resistant with subsequent infections, leading to extensive or pan-drug resistance in 4.5% of patients. The burden of an LVADi was 1862 excess hospital days, 3960 excess antibiotic days, and $3.4 million.ConclusionsPatients with LVADis had significant increases in costs, LOS, readmissions, and antibiotic usage. Antimicrobial resistance varied directly with the number of repeat infections and antibiotic exposure. Identification of factors associated with LVADi, and quantification of the burden of LVADi can inform prevention efforts and lead to reduced infection rates. As preventing infections in the first place is also important for limiting the emergence of antimicrobial resistance, we offer strategies to avoid LVADis.Trial registryNot applicable.

Computational deconvolution of cell type-specific gene expression in COPD and IPF lungs reveals disease severity associations

BackgroundChronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n > 1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity.ResultsWe analyzed lung tissue RNA-seq data from 1026 subjects (COPD, n = 465; IPF, n = 213; control, n = 348) from the Lung Tissue Research Consortium. We performed RNA-seq deconvolution, querying thirty-eight discrete cell-type varieties in the lungs. We tested whether deconvoluted cell-type abundance and cell type-specific gene expression were associated with disease severity. The abundance score of twenty cell types significantly differed between IPF and control lungs. In IPF subjects, eleven and nine cell types were significantly associated with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), respectively. Aberrant basaloid cells, a rare cells found in fibrotic lungs, were associated with worse FVC and DLCO in IPF subjects, indicating that this aberrant epithelial population increased with disease severity. Alveolar type 1 and vascular endothelial (VE) capillary A were decreased in COPD lungs compared to controls. An increase in macrophages and classical monocytes was associated with lower DLCO in IPF and COPD subjects. In both diseases, lower non-classical monocytes and VE capillary A cells were associated with increased disease severity. Alveolar type 2 cells and alveolar macrophages had the highest number of genes with cell type-specific differential expression by disease severity in COPD and IPF. In IPF, genes implicated in the pathogenesis of IPF, such as matrix metallopeptidase 7, growth differentiation factor 15, and eph receptor B2, were associated with disease severity in a cell type-specific manner.ConclusionsUtilization of RNA-seq deconvolution enabled us to pinpoint cell types present in the lungs that are associated with the severity of COPD and IPF. This knowledge offers valuable insight into the alterations within tissues in more advanced illness, ultimately providing a better understanding of the underlying pathological processes that drive disease progression.

Comparing the Accuracy and Reliability of Detecting the Intensity of Spinal Inflammation on STIR Sequence with Apparent Diffusion Coefficient Values in Axial Spondyloarthritis

Objective: To compare the accuracy and reliability of detecting the intensity of spinal inflammation on short tau inversion recovery (STIR) with the apparent diffusion coefficient (ADC) values of the active magnetic resonance imaging (MRI) lesions in axial spondyloarthritis (axSpA). Materials and methods: Fifty active lesions in the STIR sequence of spinal MRI were identified. With reference to sites of active lesions in STIR, the corresponding region of interest (ROI) on the ADC map was drawn to determine the maximum ADC (ADC[Formula: see text]), mean ADC (ADC[Formula: see text]), normalized maximum (nADC[Formula: see text]), and mean (nADC[Formula: see text]). Four independent readers scored the identified active lesions as “intense” or “non-intense” according to the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. They were compared to various ADC parameters for assessment of accuracy and reliability. Regression analyses were used to adjust potential factors that could affect ADC. Results: Significant differences were found in ADC[Formula: see text] between “intense” and “non-intense” lesions scored by three of the four readers (1,405.7 ± 271.4 vs. 1,165.8 ± 223.8, [Formula: see text] = 0.01; 1,420.7 ± 272.1 vs. 1,209.0 ± 248.5, [Formula: see text] = 0.01; 1,438.0 ± 307.2 vs. 1,213.6 ± 231.0, [Formula: see text] = 0.01). Only one reader could differentiate a difference in “intense” and “non-intense” lesions with respect to ADC[Formula: see text] (899.2 ± 248.3 vs. 711.0 ± 222.6, [Formula: see text] = 0.01) and nADC[Formula: see text] (4.4 ± 2.1 vs. 3.4 ± 1.4, [Formula: see text] = 0.05). Inter-reader agreements were slight to moderate (kappa = 0.07–0.45). Reliability substantially improved when only the lowest and highest 25th percentiles of ADC values were included (kappa = 0.17–0.75). Regression analyses showed that the “intense” lesions were associated with higher ADC values after adjustment for confounders. Conclusion: Reading of STIR MRI is limited by the lack of ability in differentiating subtle differences of spinal inflammation. ADC could be an alternative method.

A comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials

BackgroundRupture of unstable coronary atherosclerotic plaque leads to acute ST-segment elevation myocardial infarction (STEMI). Dual anti-platelet therapy is one of the main treatments, and the combination of Aspirin and Clopidogrel is recognized as the standard oral regimen in most cases. Ticagrelor is a new generation of P2Y12 receptor inhibitors. We aimed to compare the effect of Ticagrelor and Clopidogrel in the treatment of patients post-STEMI.MethodsThis study investigated Pub Med, Scopus, Google Scholar Web of Science, and Embase Cochrane Library clinical trials.gov databases. Heterogeneity between studies was assessed using the I2 index and the Q statistic. The random effects model was used to combine studies and the Funnel plot and Egger’s test were used to assess the publication bias.ResultsEleven studies were included in this meta-analysis. 5274 patients in the Ticagrelor and 5,295 patients in the Clopidogrel groups were examined. The mean age of the patients was 58.84 years (2.70) and 59.92 years (3.19) in the Ticagrelor and Clopidogrel groups, respectively. Based on the results of the meta-analysis, compared to Clopidogrel, Ticagrelor had decreased the outcomes of mortality, recurrent myocardial infarction, stroke, and Major Adverse Cardiovascular Events (MACE). However, the post-myocardial infarction bleeding according to Bleeding Academic Research Consortium (BARC) criteria and reperfusion state regarding thrombolysis in myocardial infarction (TIMI) Flow Grading system showed no differences in both groups. However, these effects were not statistically significant.ConclusionsTicagrelor decreased the chance of mortality, re-infarction, stroke, and MACE in post-STEMI patients compared to clopidogrel. But there was no difference in the chance of major bleedings (BARC ≥ 3) and improvement in TIMI grade flow between these two drugs. However, none of these findings were statistically significant, and more studies are needed to reach definitive results.

Perspectives on non-emergent neonatal intensive care unit to pediatric intensive care unit care transfers in the United States.

There is a substantial population of long-stay patients who non-emergently transfer directly from the neonatal intensive care unit (NICU) to the pediatric intensive care unit (PICU) without an interim discharge home. These infants are often medically complex and have higher mortality relative to NICU or PICU-only admissions. Given an absence of data surrounding practice patterns for non-emergent NICU to PICU transfers, we hypothesized that we would encounter a broad spectrum of current practices and a high proportion of dissatisfaction with current processes. To characterize non-emergent NICU to PICU transfer practices across the United States and query PICU providers' evaluations of their effectiveness. A cross-sectional survey was drafted, piloted, and sent to one physician representative from each of 115 PICUs across the United States based on membership in the PARK-PICU research consortium and membership in the Children's Hospital Association. The survey was administered via internet (REDCap). Analysis was performed using STATA, primarily consisting of descriptive statistics, though logistic regressions were run examining the relationship between specific transfer steps, hospital characteristics, and effectiveness of transfer. One PICU attending from each of 81 institutions in the United States completed the survey (overall 70% response rate). Over half (52%) indicated their hospital transfers patients without using set clinical criteria, and only 33% indicated that their hospital has a standardized protocol to facilitate non-emergent transfer. Fewer than half of respondents reported that their institution's non-emergent NICU to PICU transfer practices were effective for clinicians (47%) or patient families (38%). Respondents evaluated their centers' transfers as less effective when they lacked any transfer criteria (P = 0.027) or set transfer protocols (P = 0.007). Respondents overwhelmingly agreed that having set clinical criteria and standardized protocols for non-emergent transfer were important to the patient-family experience and patient safety. Most hospitals lacked any clinical criteria or protocols for non-emergent NICU to PICU transfers. More positive perceptions of transfer effectiveness were found among those with set criteria and/or transfer protocols.

Trends in antithrombotic therapy and clinical outcomes for percutaneous coronary intervention in Japan following the 2020 JCS guideline focused update: findings from the SAKURA PCI2 Antithrombotic Registry.

In April 2020, the Japanese Circulation Society updated guidelines recommending shortened dual antiplatelet therapy (DAPT) for patients at Japanese Version of the High Bleeding Risk (J-HBR), but the impact remains unclear. We conducted a prospective multicenter registry (SAKURA PCI2 Antithrombotic Registry) starting June 2020 (n = 1136), enrolling patients who underwent percutaneous coronary intervention (PCI). Planned DAPT duration, defined as short if less than 3months, was based on patient background post-PCI and physicians' discretion. Planned short DAPT was used in 55.2% of patients, with a similar incidence of J-HBR (68.3% vs. 66.6%, p = 0.55) and a shorter actual DAPT duration (97 vs. 229days, p < 0.001) compared with Planned non-short DAPT. Primary endpoints, major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, non-fatal myocardial infarction, stent thrombosis, and stroke, and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding (BARC-3/5), occurred similarly across groups (MACCE: 6.5% vs. 7.3%, p = 0.66; BARC-3/5: 3.7% vs. 2.2%, p = 0.14). Independent predictors of MACCE included age ≥ 75, Clinical Frailty Scale ≥ 4, and hemoglobin < 11. Age ≥ 75, severe chronic kidney disease, hemoglobin < 11, and platelets < 100,000 were linked to BARC-3/5. Among BARC 3/5 patients, 41.2% experienced bleeding after switching to single antiplatelet therapy. Planned short DAPT was implemented in 55.2% of patients, showing comparable thrombotic and bleeding outcomes to non-short DAPT.

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them. Responding to the needs of researchers within the CCNA teams, a unique sample of 1173 deeply phenotyped patients with various forms of dementia was accrued and studied over eight years (COMPASS-ND). In the second phase of funding (2019-2024), a national dementia prevention program (CAN-THUMBS UP) was set up. In a short time, this prevention program became a member of the World Wide FINGERS prevention consortium. In this article, the challenges, successes, and impacts of CCNA in Canada and internationally are discussed. Short-term deliverables have occurred, along with considerable promise of impacts in the longer term. The creation of synergy, networking, capacity building, engagement of people with lived experience, and economies of scale have contributed to the considerable success of CCNA by all measures. CCNA is evidence that an organized "centrally-organized" approach to dementia research can catalyze important progress nationally and yield significant and measurable results.

Legal obstacles jeopardise research in personalised medicine - experiences from a Nordic collaboration within rheumatology.

Personalised medicine in chronic complex diseases such as rheumatoid arthritis (RA) is within reach but requires international multi-stakeholder collaboration. We exemplify how national implementations of the General Data Protection Regulation (GDPR) have introduced administrative delays and created disincentives for data sharing and collaborative research. Our Danish/Swedish/Norwegian research collaboration (the 3-year NordForsk-funded "NORA" project) aims to develop a personalised medicine approach for the management of RA, built on the exploitation of unique existing data sources: longitudinal data from clinical rheumatology registries, research cohorts, nationwide health care registries, and biobank material from >20 sample collections. Data and results are shared and accessed remotely by collaborators at secure servers. New biomarker assays and patient-centric implementations of the results are to be explored, validated, and disseminated to patients and health care via the development of digital tools. Following the advice of legal experts at the involved academic or public institutions and private companies, GDPR compliance resulted in >20 legal documents to govern the collaboration (consortium-, joint controller-, research collaboration-, data sharing-, and a series of unique two-way data processing-, and material transfer agreements). Lack of agreed-upon templates, policies, procedures, and a shortage of legal resources have caused considerable delays. Thus, our research consortium has spent more time ensuring GDPR compliance than on actual research activities. The current interpretation and implementation of the legal premises (rather than the GDPR per se) for research collaborations caused unnecessary barriers and delays. Our experiences call for Nordic trust-based code-of-conduct-like framework agreements, and for harmonisation of procedures and templates, lest the Nordic advantage in research be lost.

Governance of responsible research and innovation: A social welfare, psychologically grounded multicriteria decision analysis approach

Our article deals with the governance of responsible research and innovation (RRI) and aims to set out a first psychologically grounded decision-theoretic method for the governance of RRI. We approach the governance of RRI as a multicriteria group decision analysis problem of delivering social welfare in an innovation ecosystem. Following such a methodological approach, we develop a psychologically grounded multicriteria group decision analysis method that integrates in its value function the main psychological effects captured in the value function of prospect theory as the main theory of individual decision-making under risk. The method first applies a psychologically motivated multicriteria decision analysis function that measures the welfare delivered to all stakeholders involved in a research and innovation consortium. The method then applies a social welfare function on the welfare measurements of stakeholders to propose a social welfare solution that emerges as an RRI-compliant solution for the consortium. The results are a first psychologically grounded multicriteria group decision analysis method and its first application to the governance of RRI. The implications of our results are theoretical but also practical, as our method contributes not only to the established field of multicriteria decision analysis by setting out new method but also to the field of RRI by delivering a psychologically grounded decision-theoretic general method for the governance of RRI.

A Spectroscopic and Interferometric Study of W Serpentis Stars. I. Circumbinary Outflow in the Interacting Binary W Serpentis

W Serpentis is an eclipsing binary system and the prototype of the Serpentid class of variable stars. These are interacting binaries experiencing intense mass transfer and mass loss. However, the identities and properties of both stars in W Ser remain a mystery. Here, we present an observational analysis of high-quality, visible-band spectroscopy made with the Apache Point Observatory 3.5 m telescope and Astrophysical Research Consortium Echelle Spectrograph spectrograph plus the first near-IR, long-baseline interferometric observations obtained with the Center for High Angular Resolution Astronomy Array. We present examples of the appearance and radial velocities of the main spectral components: prominent emission lines, strong shell absorption lines, and weak absorption lines. We show that some of the weak absorption features are associated with the cool mass donor, and we present the first radial velocity curve for the donor star. The donor’s absorption lines are rotationally broadened, and we derive a ratio of donor to gainer mass of 0.36 ± 0.09 based on the assumptions that the donor fills its Roche lobe and that it rotates synchronously with the orbit. We use a fit of the All-Sky Automated Survey light curve to determine the orbital inclination and mass estimates of 2.0M ⊙ and 5.7M ⊙ for the donor and gainer, respectively. The partially resolved interferometric measurements of orbital motion are consistent with our derived orbital properties and the distance from Gaia EDR3. Spectroscopic evidence indicates that the gainer is enshrouded in an opaque disk that channels the mass transfer stream into an outflow through the L3 region and into a circumbinary disk.

Pandemic Perceptions and Healthcare Decisions: Exploring Perceived COVID-19 Threat’s Impact on Perinatal Healthcare in Florida

The COVID-19 pandemic directly impacted well-being and healthcare delivery, but its indirect effects on health services utilization among pregnant women and new mothers remain less understood. Understanding how big events like pandemics impact health behaviors is essential for anticipating healthcare needs during future crises. This study examined how the perceived COVID-19 threat influenced health concerns and service utilization among 378 participants who were either pregnant or mothers of infants less than 12 months old, 18 years or older, and lived within a 50-mile radius of healthcare sites in the OneFlorida+ Clinical Research Consortium. An online Qualtrics survey assessed COVID-19 threat perception, distress related to health and resource concerns (e.g., access to medicine, baby supplies, mental and general healthcare, and social interactions), and changes to health service utilizations (e.g., induction schedule, hospital/birthing center choices, prenatal provider, and visit frequency) during the pandemic. Participants who perceived COVID-19 as a significant threat were likelier to report concerns about reduced access to general healthcare (p = 0.043). Pregnant participants, compared to mothers with infants under 12 months of age, expressed greater concern about reduced access to mental healthcare (p = 0.015). Additionally, the perceived COVID-19 threat was linked to changes in prenatal care providers and labor induction schedules (p &lt; 0.001). These findings highlight the importance of integrating the perceived threat of pandemics or other major events into mental health screenings. Healthcare providers should proactively address potential changes in patient behavior during major events in anticipation of future crises. Keywords: pregnancy, COVID-19, mental healthcare, prenatal healthcare utilization, perceived COVID-19 threat

Major Bleeding and Mortality After Revascularization of Left Main Disease

BackgroundThe incidence and prognostic impact of major bleeding (MB) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) are unknown. ObjectivesThe goal of this study was to investigate the rates and outcomes of MB after LMCAD revascularization. MethodsIn the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with unprotected LMCAD were randomized to undergo PCI (n = 948) or CABG (n = 957) and followed up for 5 years. MB was defined as TIMI major or minor bleeding, BARC (Bleeding Academic Research Consortium) types 3 to 5 bleeding, or any overt bleeding requiring blood transfusion. The association between MB and subsequent mortality was assessed in time-adjusted Cox regression models. ResultsAt 5 years, 217 patients (11.4%) had at least 1 MB event. Rates of 5-year MB were 7.9% after PCI vs 14.8% after CABG (OR: 0.48; 95% CI: 0.36-0.65; P < 0.0001). However, in-hospital MB was lower after PCI (3.8% vs 13.5%; OR: 0.25; 95% CI: 0.17-0.37), whereas postdischarge MB was lower after CABG (4.5% vs 2.0%; OR: 2.33; 95% CI: 1.33-3.09; Pinteraction < 0.0001). All 41 postdischarge MB events after PCI occurred in patients receiving dual antiplatelet therapy. MB events within 5 years were associated with a higher subsequent risk of all-cause mortality (adjusted HR: 2.71; 95% CI: 1.95-3.77; P < 0.0001), whether in-hospital or postdischarge (Pinteraction = 1.00) and after both PCI and CABG (Pinteraction = 0.95), driven both by increased cardiovascular and non-cardiovascular mortality. ConclusionsIn the EXCEL trial, CABG resulted in higher 5-year rates of all MB and in-hospital MB, although postdischarge MB was more frequent after PCI. MB after both procedures was associated with increased cardiovascular and noncardiovascular mortality within 5 years. (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)

The immune cells causative role in lung cancer: Mendelian randomization study

BackgroundsLung cancer (LC) is the leading cause of cancer-related deaths in China, with its incidence and mortality rates rising annually. Various studies have demonstrated disparities in immune cell counts and profiles between LC patients and healthy individuals. However, the existence of a causal link remains largely uncertain. To explore the potential causal association between immune cells and LC risk, a Mendelian randomization (MR) approach was employed.MethodsEmploying immune cell genome-wide association study (GWAS) data from a public database (n = 731 subjects) and Lung Cancer Genome Research Consortium's GWAS dataset (n = 492,803 participants), unconventional genetic loci remarkably associated with the significant abundance of 731 types of immune cells were extracted according to preset threshold points as instrumental variables. The primarily analytical strategy involved the inverse variance weighting (IVW) method, with the effect size estimates expressed as odds ratio (OR) and 95% CI. The robustness of the findings was assessed through a leave-one-out sensitivity analysis, heterogeneity test, horizontal gene pleiotropy test, MR-PRESSO and MR-Egger.ResultsThe MR analysis identified a significant association between 18 distinct immune cell types and lung cancer risk. MR analysis revealed that 7 types of immune cells, including CD20 on IgD − CD38 − B cell, CD20 on switched memory B cell, IgD on IgD + CD24 + B cell, BAFF − R on IgD − CD38 + B cell, CD39 + resting CD4 regulatory T cell Absolute Count, CD127 on CD45RA + CD4 + T cell, CD8 on Effector Memory CD8 + T cell, displayed a protective effect against lung cancer development. Conversely, 11 other immune cells populations were positive associated with an increased lung cancer risk. In contrast, reverse MR analysis indicated that the lung cancer risk was linked to 11 immune cells, with 2 types of immune cells (CD25 on IgD − CD27 − B cell, CD4 + T cell %leukocyte) showing a are positive correlation with cancer development, whereas 9 types of immune cells appeared to be inversely regulated. These findings collectively imply that specific immune cell populations may play critical roles in either promoting or suppressing the initiation and progression of lung cancer.ConclusionThe findings of this study offer fresh insights into the underlying biological mechanisms governing lung cancer development, thereby opening new avenues for future research in the domain of LC. The identification of specific immune cell subsets with protective or promoting roles provides crucial leads for preventive and therapeutic strategies. These insights have the potential to enhance early detection methods and inform the development of more effective treatment approaches, ultimately benefiting patient outcomes and improving the overall management of lung cancer.

Early outcomes of the novel Myval THV series compared to SAPIEN THV series and Evolut THV series in individuals with severe aortic stenosis.

There are limited head-to-head randomised trials comparing the performance of different transcatheter heart valves (THVs). We aimed to evaluate the non-inferiority of the balloon-expandable Myval THV series compared to the balloon-expandable SAPIEN THV series or the self-expanding Evolut THV series. The LANDMARK trial randomised 768 patients in a 1:1 ratio, (Myval THV series [n=384] vs contemporary series with 50% SAPIEN THV series [n=192] and 50% Evolut THV series [n=192]). The non-inferiority of Myval over the SAPIEN or Evolut THV series in terms of the 30-day primary composite safety and effectiveness endpoint as per the third Valve Academic Research Consortium (VARC-3) was tested in an intention-to-treat population with a predefined statistical power of 80% (1-sided alpha of 5%) for a non-inferiority margin of 10.44%. The Myval THV series achieved non-inferiority for the primary composite endpoint over the SAPIEN THV series (24.7% vs 24.1%, risk difference [95% confidence interval {CI}]: 0.6% [not applicable {NA} to 8.0]; p=0.0033) and the Evolut THV series (24.7% vs 30.0%, risk difference [95% CI]: -5.3% [NA to 2.5]; p<0.0001). The incidences of pacemaker implantation were comparable (Myval THV series: 15.0%, SAPIEN THV series: 17.3%, Evolut THV series: 16.8%). At 30 days, the mean pressure gradient and effective orifice area were significantly better with the Myval THV series compared to the SAPIEN THV series (p<0.0001) and better with the Evolut THV series than with the Myval THV series (p<0.0001). At 30 days, the proportion of moderate to severe prosthetic valve regurgitation was numerically higher with the Evolut THV series compared to the Myval THV series (7.4% vs 3.4%; p=0.06), while not significantly different between the Myval THV series and the SAPIEN THV series (3.4% vs 1.6%; p=0.32). The Myval THV series is non-inferior to the SAPIEN THV series and the Evolut THV series in terms of the primary composite endpoint at 30 days. ClinicalTrials.gov: NCT04275726; EudraCT number 2020-000,137-40.

TAVI with the ACURATE neo2 in severe bicuspid aortic valve stenosis: the Neo2 BAV Registry.

The ACURATE neo2 is a contemporary transcatheter aortic valve implantation (TAVI) system approved for the treatment of severe aortic stenosis in Europe. The ACURATE neo2 has not been evaluated in bicuspid aortic valve (BAV) stenosis. We sought to evaluate the safety and efficacy of ACURATE neo2 in patients with BAV stenosis. We retrospectively analysed consecutive severe BAV stenosis patients undergoing TAVI with ACURATE neo2 at 10 European centres. Imaging data from preprocedural multislice computed tomography, pre- and postprocedural echocardiography, and procedural cinefluoroscopy were evaluated by a core laboratory. Valve Academic Research Consortium 3 (VARC-3)-defined 30-day procedure safety and efficacy were the primary endpoints. Adverse events were site-reported according to VARC-3 criteria. Among 181 patients with BAV stenosis treated with the ACURATE neo2, the mean age was 77.5±7.2 years, 58.0% were female, and the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 2.3% (1.6-3.7%). Most procedures were transfemoral, and predilatation was performed in all cases. A second valve was required in 4 cases (2.2%). VARC-3-defined technical success was 95.6%. The primary endpoints of device success and early safety occurred in 90.6% and 82.3%, respectively. At 30 days, cardiovascular death occurred in 2.2% (N=4) and stroke in 1.6% (N=3). Core laboratory-adjudicated echocardiography reported an effective orifice area of 2.0 (1.7-2.5) cm2 and a mean transvalvular gradient of 6.5 (4.6-9.0) mmHg. Half of all cases (51.2%) had no paravalvular leak, while moderate leak occurred in 4.3%. A new permanent pacemaker was required in 11 patients (6.5%). The ACURATE neo2 demonstrated favourable clinical outcomes and bioprosthetic valve performance at 30 days in selected patients with severe BAV stenosis.

Seasonal variations in the association between proteinuria, CKD, and kidney failure.

Proteinuria exhibits seasonal fluctuations, decreasing in summer and increasing in winter. It is unknown whether the association between proteinuria and the risk of kidney failure varies by season. The Osaka Consortium for Kidney Disease Research (OCKR) database contained retrospective data from 15 367 patients with estimated glomerular filtration rates of 10-60mL/min/1.73m2, who were referred to the Department of Nephrology at five clinical centers in Japan, between 2010 and 2021. Multivariate Cox models were used to examine the associations of urinary protein-to-creatinine ratio (UPCR) in summer (UPCRsummer) and winter (UPCRwinter) with kidney failure defined as initiation of kidney replacement therapy. LASSO was used to compare the strength of the association between UPCRsummer and UPCRwinter with respect to kidney failure. We also assessed whether seasonal fluctuations in UPCR were associated with kidney failure. The median [interquartile range] UPCRwinter was 0.89 [0.22, 2.69] g/gCre, 46% higher than UPCRsummer (0.61 [0.16, 1.87] g/gCre). During a median follow-up of 3.0 years, 1 585 patients developed kidney failure. In time-dependent Cox models, UPCRwinter showed a higher hazard of kidney failure (1.66 per 1-standard deviation [SD] increase; 95% confidence interval [CI], 1.60-1.73) than UPCRsummer (1.45 per 1-SD increase; 95%CI, 1.41-1.48). LASSO identified that UPCRwinter was more strongly associated with kidney failure than UPCRsummer. Furthermore, higher % changes in UPCRwinter relative to UPCRsummer was associated with a higher hazard of kidney failure. Proteinuria in winter exhibited stronger associations with kidney failure than that in summer. Seasonal fluctuations in UPCR should not be overlooked in the management of CKD to make reasonable clinical decisions.

Proceedings of the 18th annual meeting of the Genetic Epidemiology of Parkinson's disease consortium.

The 18th annual meeting of the Genetic Epidemiology of Parkinson's disease (GEoPD) consortium was held on October 30th and 31st, 2023 in the city of Antwerpen (Belgium). GEoPD is a global consortium of researchers dedicated to promoting education, basic and translational research in Parkinson's disease. The consortium has been operating since 2004, and has an active membership from numerous sites on six continents. We were very proud to have scientific participation from renowned clinicians and researchers from different continents. The meeting featured invited oral presentations and poster sessions on genetic stratification, pathogenesis, biomarkers, diagnosis and treatment of Parkinson's disease. In these proceedings of the meeting, we have included abstracts of oral plenary presentations and abstracts of poster presentations.

Using Artificial Intelligence to Identify Three Presenting Phenotypes of Chiari Type-1 Malformation and Syringomyelia

BACKGROUND AND OBJECTIVES: Chiari type-1 malformation (CM1) and syringomyelia (SM) are common related pediatric neurosurgical conditions with heterogeneous clinical and radiological presentations that offer challenges related to diagnosis and management. Artificial intelligence (AI) techniques have been used in other fields of medicine to identify different phenotypic clusters that guide clinical care. In this study, we use a novel, combined data-driven and clinician input feature selection process and AI clustering to differentiate presenting phenotypes of CM1 + SM. METHODS: A total of 1340 patients with CM1 + SM in the Park Reeves Syringomyelia Research Consortium registry were split a priori into internal and external cohorts by site of enrollment. The internal cohort was used for feature selection and clustering. Features with high Laplacian scores were identified from preselected groups of clinically relevant variables. An expert clinician survey further identified features for inclusion that were not selected by the data-driven process. RESULTS: The feature selection process identified 33 features (28 from the data-driven process and 5 from the clinician survey) from an initial pool of 582 variables that were incorporated into the final model. A K-modes clustering algorithm was used to identify an optimum of 3 clusters in the internal cohort. An identical process was performed independently in the external cohort with similar results. Cluster 1 was defined by older CM1 diagnosis age, small syringes, lower tonsil position, more headaches, and fewer other comorbidities. Cluster 2 was defined by younger CM1 diagnosis age, more bulbar symptoms and hydrocephalus, small syringes, more congenital medical issues, and more previous neurosurgical procedures. Cluster 3 was defined by largest syringes, highest prevalence of spine deformity, fewer headaches, less tonsillar ectopia, and more motor deficits. CONCLUSION: This is the first study that uses an AI clustering algorithm combining a data-driven feature selection process with clinical expertise to identify different presenting phenotypes of CM1 + SM.

Sample Article for Pree Reviewer

Background Large research consortia can generate tremendous amounts of biological information, including high-resolution soil, vegetation, and climate data. While this knowledge stock holds invaluable potential for answering evolutionary and ecological questions, making these data exploitable for modelling remains a daunting task due to the many processing steps required for synthesis. This might result in many researchers to fall back to a handful of ready-to-use data sets, potentially at the expense of statistical power and scientific rigour. In a push for a more stringent approach, we introduce BEpipeR, an R pipeline that allows for the streamlined synthesis of plot-based Biodiversity Exploratories data. Methods BEpipeR was designed with flexibility and ease of use in mind. For instance, users simply choose between aggregating forest or grassland data, or a combination thereof, effectively allowing them to process any experimental plot data of this research consortium. Additionally, instead of coding, they parse most processing information in a user-friendly way through parameter sheets. Processing includes, among others, the creation of a spatially explicit plot-ID template, data wrangling, quality control, plot-wise aggregations, the calculation of derived metrics, data joining to a large composite data set, and metadata compilation. Results With BEpipeR, we provide a feature-rich pipeline that allows users to process Biodiversity Exploratories data in a flexible and reproducible way. This pipeline might serve as a starting point for aggregating the numerous data sets of this and potentially similar research consortia. In this way, it might be a primer for the construction of consortia-wide composite data sets that take full advantage of the consortia’s rich information stocks, ultimately boosting the visibility and participation of individual research projects. Conclusions The BEpipeR permits the user-friendly processing and plot-wise aggregation of Biodiversity Exploratories data. With modifications, this framework may be easily adopted by other research consortia.

Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium

ObjectivesTo identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.MethodsIn the multicentre PsA Research Consortium...