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Background: The MitraCut procedure employs beating heart transapical (TA) cannulation and endoscopic scissors for dividing the anterior mitral leaflet (AML) to prevent left ventricular outflow tract (LVOT) obstruction in transapical transcatheter mitral valve replacement (TA-TMVR)., Aims: We present the first multicentre experience of the MitraCut procedure prior to TA-TMVR to prevent LVOT obstruction., Methods: In 6 European centres, the clinical outcomes of all 13 high-risk patients who had undergone the MitraCut procedure during TA-TMVR procedures were retrospectively reviewed regarding technical success, procedural details and outcome., Results: The MitraCut procedure was successfully completed in 11 patients with 1 cutting attempt, while 2 patients had 2 cutting attempts, with an average procedure duration of 9.0±5.4 min. No patient demonstrated postoperative LVOT obstruction, and all mitral valve (MV) prostheses were competent throughout the follow-up period. However, 1 patient developed a MitraCut-related paravalvular leak (PVL; technical success rate: 12/13). The mean LVOT gradient was 3.9±4.4 mmHg directly after valve expansion and 3.6±3.1 mmHg at follow-up. In-hospital and 30-day mortality were 0%. One patient experiencing MitraCut-related PVL was successfully treated by interventional PVL closure (reintervention rate: n=1). One patient died at 47 days due to cardiac arrhythmia, unrelated to the AML-directed procedure. The mean follow-up at the time of data analysis was 52±34 days., Conclusions: The MitraCut procedure was effective and reproducible for preventing potential LVOT obstruction in TA-TMVR patients during its initial exploration in 6 European hospitals. Considerations regarding the scissors' characteristics, their handling and cut length are mandatory for safe performance of the procedure.

Ultrafine particles (UFP) are the smallest atmospheric particulate matter linked to air pollution-related diseases. The extent to which UFP's physical and chemical properties contribute to its toxicity remains unclear. It is hypothesized that UFP act as carriers for chemicals that drive biological responses. This study explores robust methods for generating reference UFP to understand these mechanisms and perform toxicological tests. Two types of combustion-related UFP with similar elemental carbon cores and physical properties but different organic loads were generated and characterized. Human alveolar epithelial cells were exposed to these UFP at the air-liquid interface, and several toxicological endpoints were measured. UFP were generated using a miniCAST under fuel-rich conditions and immediately diluted to minimize agglomeration. A catalytic stripper and charcoal denuder removed volatile gases and semi-volatile particles from the surface. By adjusting the temperature of the catalytic stripper, UFP with high and low organic content was produced. These reference particles exhibited fractal structures with high reproducibility and stability over a year, maintaining similar mass and number concentrations (100 μg/m 3 , 2.0·10 5 #/cm 3 ) and a mean particle diameter of about 40 nm. High organic content UFP had significant PAH levels, with benzo[a]pyrene at 0.2 % (m/m). Toxicological evaluations revealed that both UFP types similarly affected cytotoxicity and cell viability, regardless of organic load. Higher xenobiotic metabolism was noted for PAH-rich UFP, while reactive oxidation markers increased when semi-volatiles were stripped off. Both UFP types caused DNA strand breaks, but only the high organic content UFP induced DNA oxidation. This methodology allows modification of UFP's chemical properties while maintaining comparable physical properties, linking these variations to biological responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Among Veterans Health Administration (VHA) patients receiving internet-connected tablets, we examined (1) app usage, (2) clusters of commonly used apps and patient characteristics across clusters, and (3) the relationship between app clusters and mental health services., Materials and Methods: A survey was distributed to a national sample of VHA patients ( n  = 5449) within 6 months of tablet receipt. Self-reported app use was clustered with agglomerative hierarchical clustering. Survey data were combined with electronic health record data that included sociodemographics and mental health care utilization during the 6 months following survey completion. Differences in patient characteristics by cluster were examined using chi-square tests. A multivariable model assessed prediction of mental health services across app clusters., Results: Among 1664 patients with complete survey and health care utilization data, the majority (74%) reported using at least 1 app. The most used apps were for video visits (60%) and VA's patient portal (53%). Cluster analysis revealed 5 distinct groups reflecting app usage: Patient Portal ( n  = 685, 41%), Video Connection ( n  = 319, 19%), Treatment Companion ( n  = 166, 10%), Self-Management ( n  = 85, 5%), and Non-App Group ( n  = 409, 25%). Cluster characteristics varied, and those in the Patient Portal Group (adjusted odds ratio  = 1.64; 95% CI = 1.15-2.32) and Video Connection Group (adjusted odds ratio = 1.52; 95% CI = 1.02-2.26) were more likely to have a mental health visit in the 6 months after survey completion when compared to the Non-App Group ( P  < .05)., Discussion: Tablet provision supports opportunities to use apps for multiple health management tasks, and app use clusters vary across patient characteristics and health care utilization., Conclusion: Patients most commonly used apps to connect with their care team, and use of some apps and app combinations may improve engagement with mental health services., Competing Interests: None declared., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analysed subsequent memory functional MRI data from individuals with SCD, MCI and AD dementia as well as healthy controls and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-centre DELCODE study (n = 468). Based on the individual participants' whole-brain functional MRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity and APOE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to healthy controls, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ɛ4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Sulphur Emission Control Areas (SECAs), mandated by the International Maritime Organization (IMO), regulate fuel sulphur content (FSC) to mitigate the environmental and health impact of shipping emissions in coastal areas. Currently, FSC is limited to 0.1% (w/w) within and 0.5% (w/w) outside SECAs, with exceptions for ships employing wet sulphur scrubbers. These scrubbers enable vessels using non-compliant fuels such as high-sulphur heavy fuel oils (HFOs) to enter SECAs. However, while sulphur reduction via scrubbers is effective, their efficiency in capturing other potentially harmful gases remains uncertain. Moreover, emerging compliant fuels like highly aromatic fuels or low-sulphur blends lack characterisation and may pose risks. Over three years, we assessed emissions from an experimental marine engine at 25% and 75% load, representative of manoeuvring and cruising, respectively. First, characterizing emissions from five different compliant and non-compliant fuels (marine gas oil MGO, hydro-treated vegetable oil HVO, high-, low- and ultra-low sulphur HFOs), we calculated emission factors (EF). Then, the wet scrubber gas-phase capture efficiency was measured using compliant and non-compliant HFOs. NO x EF varied among fuels (5200-19700 mg/kWh), with limited scrubber reduction. CO (EF 750-13700 mg/kWh) and hydrocarbons (HC; EF 122-1851 mg/kWh) showed also insufficient abatement. Carcinogenic benzene was notably higher at 25% load and about an order of magnitude higher with HFOs compared to MGO and HVO, with no observed scrubber reduction. In contrast, carbonyls such as carcinogenic formaldehyde and acetaldehyde, acting as ozone precursors, were effectively scrubbed due to their polarity and water solubility. The ozone formation potential (OFP) of all fuels was examined. Significant EF differences between fuels and engine loads were observed, with the wet scrubber providing limited or no reduction of gaseous emissions. We suggest enhanced regulations and emission abatements in the marine sector to mitigate gaseous pollutants harmful to human health and the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Brief integrated care settings hold promise for accessible and effective trauma-informed interventions. However, clinicians often have difficulty efficiently forecasting who is most appropriate for interventions in such settings and how to target individualized care. Multidimensional and transdiagnostic evaluations may provide valuable information to improve stepped-care and treatment practices for veterans., Method: A middle-out approach was used to concurrently evaluate self-reported posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, and physical health problems using cross-sectional (latent profile analysis) and longitudinal (latent growth mixture modeling) analyses that identified unique symptom profiles, trajectories of traumatic stress reactions, and correlates of these health outcomes. Data from 234 veterans who participated in a randomized controlled trial of primary care PTSD intervention were analyzed at 0, 8, 16, and 24 weeks., Results: Latent profile analysis identified two homogenous baseline profiles: global symptoms (33.8%); low dysphoria-lower negative cognitions, mood, and depressive symptoms (66.2%). Low dysphoria participants reported more social relationships ( OR = 1.32) and fewer environmental ( OR = 0.89) and financial ( OR = 0.23-0.35) stressors. Latent growth mixture modeling identified three trajectories: (a) reducing symptoms ("responders"; 21.3%) and chronic symptoms of (b) moderate (59.6%) and (c) high (19.1%) severity. Low dysphoria participants were 4.35 times more likely to be responders over time compared to participants with moderate severity symptoms., Conclusions: Findings indicated that veterans with moderate PTSD symptoms and physical health problems but low dysphoria may respond best to trauma-informed intervention in brief integrated care settings, while others may require further individualized stepped care. Findings demonstrate unique traumatic stress reactions that support individualized stepped care and may offer greater treatment utilization, retention, and efficacy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The interrelationship between climate change, pollution and the aerobiome (the microbiome of the air) is a complex ecological dynamic with profound implications for human and ecosystem health. This mini-review explores the multifaceted relationships among these factors. By synthesising existing research and integrating interdisciplinary perspectives, we examine the mechanisms driving interactions within the climate change-pollution-aerobiome nexus. We also explore synergistic and cascading effects and potential impacts on human health (including both communicable and non-communicable diseases) and that of wider ecosystems. Based on our mini-review results, climate change influences air pollution and, independently, air pollution affects the composition, diversity and activity of the aerobiome. However, we apply a 'systems thinking' approach and create a set of systems diagrams to show that climate change likely influences the aerobiome (including bacteria and fungi) via climate change-pollution interactions in complex ways. Due to the inherent complexity of these systems, we emphasise the importance of holistic and/or interdisciplinary approaches and collaborative efforts in understanding this nexus to safeguard planetary health in an era of rapid environmental change., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Objectives: The US Agency for Healthcare Research and Quality, through the Evidence-based Practice Center (EPC) Program, aims to provide health system decision makers with the highest-quality evidence to inform clinical decisions. However, limitations in the literature may lead to inconclusive findings in EPC systematic reviews (SRs). The EPC Program conducted pilot projects to understand the feasibility, benefits, and challenges of utilizing health system data to augment SR findings to support confidence in healthcare decision-making based on real-world experiences., Study Design and Setting: Three contractors (each an EPC located at a different health system) selected a recently completed SR conducted by their center and identified an evidence gap that electronic health record (EHR) data might address. All pilot project topics addressed clinical questions as opposed to care delivery, care organization, or care disparities topics that are common in EPC reports. Topic areas addressed by each EPC included infantile epilepsy, migraine, and hip fracture. EPCs also tracked additional resources needed to conduct supplemental analyses. The workgroup met monthly in 2022-2023 to discuss challenges and lessons learned from the pilot projects., Results: Two supplemental data analyses filled an evidence gap identified in the SRs (raised certainty of evidence, improved applicability) and the third filled a health system knowledge gap. Project challenges fell under three themes: regulatory and logistical issues, data collection and analysis, and interpretation and presentation of findings. Limited ability to capture key clinical variables given inconsistent or missing data within the EHR was a major limitation. The workgroup found that conducting supplemental data analysis alongside an SR was feasible but adds considerable time and resources to the review process (estimated total hours to complete pilot projects ranged from 283 to 595 across EPCs), and that the increased effort and resources added limited incremental value., Conclusion: Supplementing existing SRs with analyses of EHR data is resource intensive and requires specialized skillsets throughout the process. While using EHR data for research has immense potential to generate real-world evidence and fill knowledge gaps, these data may not yet be ready for routine use alongside SRs., Competing Interests: Declaration of competing interest The authors have no relevant financial relationships to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study delineated the unmet mental health needs of peripartum mothers with symptoms of depression, ascertained their willingness to engage in psychotherapy via text message, and identified potential determinants of that willingness (e.g., demographics, preferred communication methods) to inform improvement to service delivery. Method: This was a cross-sectional national survey of 897 adults who had given birth in the previous 24 months, had at least one lifetime symptom of depression, had internet access, and could read English. Univariate analysis was followed by multivariable Firth's logistic regression. Results: Peripartum participants with at least one symptom of depression wanted mental health care the most within 2 years of giving birth (64.4%) and had less access to mental health care during pregnancy and postpartum (35.1% and 38.1%, compared with 23.9%). Fifty-three percent of participants were willing to engage in psychotherapy via text message. Determinants of willingness to engage in text message therapy for all periods (pregnancy, postpartum, and not peripartum) included wanting mental health treatment but not having access and previous experience with psychotherapy via text message. During pregnancy and not peripartum, more depressive symptoms were associated with willingness to engage in psychotherapy via text message. Conclusion: The peripartum period is an especially high-risk time for mothers to experience depressive symptoms. In general, most wanted therapy but were unable to access it. Most participants were willing to engage in text message therapy.

Competing Interests: Funding Support and Author Disclosures Dr Curio has received research grant support from Boston Scientific. Dr Wienemann has received travel grants from JenaValve. Dr Adam has received personal fees from Abbott, JenaValve, Medtronic, and Meril. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Gene therapy is an important tool for treating fetal diseases that allows for the delivery and integration of therapeutic genes into the genome of cells carrying mutations. Nanomolecules, like PAMAM dendrimers, have recently come into wider use for carrying vectors as they have several advantages over viral vectors. Namely, (1) tunable size and surface chemistry, (2) uniform size, (3) the ability to target specific tissues, and (4) the ability to carry large biomolecules and drugs. Recently, we demonstrated that 4th generation (G4) PAMAM dendrimer with a cystamine core and a non-toxic surface having 90% -OH and 10% -NH 2 groups (D-Cys) could cross the blood-brain barrier following injection into the bloodstream. In the current study, as a proof of concept, we delivered the dendrimers alone (D-Cys) tagged with Cy5.5 (D-Cys-cy5.5) to healthy pregnant C57BL/6J mice to determine the fate of these dendrimers in the pregnant mice as well as in the fetus. Systematic diffusion of the D-Cys-cy5.5 was evaluated on gestational day 17 (3 days after injection) using in vivo imaging. This revealed that the dendrimer was taken up into circulation and away from the injection site. Analysis of sections by fluorescence microscopy showed that D-Cys-cy5.5 was able to successfully cross the maternal blood-brain barrier. However, analysis of the fetal brains failed to detect dendrimers in the central nervous system (CNS). Instead, they appeared to be retained in the placenta. This is one of the first studies to analyze the distribution of surface-modified PAMAM dendrimer in the pregnant mouse and fetus following systemic injection., (© 2024. The Author(s).)

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients' perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement., (© 2024. The Author(s).)

Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies., Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models., Results: In the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings., Discussion: Aβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials., Highlights: SCD in amyloid-positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Hematopoietic stem cell transplantation (HCT) is an intensive and invasive procedure used in cancer treatment that can lead to posttraumatic stress disorder (PTSD) symptoms. These symptoms are frequently overlooked in oncology and general health care settings. The suitability and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) within the cancer population remains uncertain. This study aims to evaluate its performance as a brief (five-item) case-finding screening alternative to the longer (20-item) PTSD Checklist for DSM-5 (PCL-5) in survivors who received an HCT 1 to 5 years ago., Methods: A total of 817 cancer survivors completed the PC-PTSD-5 and PCL-5 during recruitment for a randomized clinical trial. Optimal cut scores for identifying probable PTSD and item performance were determined using indices correcting for chance and item response theory analyses., Results: Of the HCT sample, 10.4% screened as positive for probable DSM-5 PTSD using the PCL-5. The PC-PTSD-5 exhibited strong internal consistency and significant associations with PCL-5 scores (total, r = .82; items, rs = .56-.61). A cutoff score of 2 provided optimal sensitivity for screening (κ[Se] = .95), whereas a cut score of 4 demonstrated the highest efficiency for detecting a probable DSM-5 PTSD diagnosis on the PCL-5 (κ[Eff] = .39). Item response theory analyses indicated that item 4 (numbing) of the PC-PTSD-5 yielded the most informative data, with other items potentially lacking incremental utility., Conclusion: Although not an instrument validation study, these findings offer efficient evidence for using the PC-PTSD-5 as a succinct screening tool among cancer survivors in a clinical context., Trials Registration: ClinicalTrials.gov, NCT04058795, registered 8/16/2019., (© 2024 American Cancer Society.)

Background: Long-term use of opioids does not result in significant clinical improvement and has shown more adverse than beneficial effects in chronic pain conditions. When opioids cause more adverse effects than benefits for the patient, it may be necessary to initiate a process of deprescribing., Aim: To explore the perceptions of French pain physicians regarding the process of opioid deprescribing in patients experiencing chronic non-cancer and to generate an understanding of the barriers and levers to the deprescribing process., Methods: We conducted a multicentric observational study with qualitative approach. Individual semi-structured interviews exploring pain physicians' perceptions, beliefs, and representations to assess the determinants of opioid deprescribing with an interview guide were used. After checking the transcripts, an inductive and independent thematic analysis of the interviews was to extract meaningful themes from the dataset., Results: Twelve pain physicians were interviewed. The main obstacles to deprescribing revolved around patient-specific attributes, characteristics of the opioids themselves, and limitations within the current healthcare system, that hinder optimal patient management. Conversely, patient motivation and education, recourse to hospitalization in a Pain Department with multidisciplinary care, follow-up by the general practitioner, and training and information dissemination among patients and clinicians emerged as facilitative elements for opioid deprescribing., Conclusion: This study underscores the needs to improve the training of healthcare professionals, the effective communication of pertinent information to patients, and the establishment of a therapeutic partnership with the patient. It is therefore essential to carry out the deprescribing process in a collaborative and interprofessional manner, encompassing both pharmaceutical and non-pharmaceutical strategies., (© 2024 World Institute of Pain.)

Objective: Mindfulness training can relieve posttraumatic stress disorder (PTSD) symptoms in military veterans and others but is inconsistently accessible. Self-guided mobile apps could improve access but their acceptability, feasibility, and benefits for veterans with PTSD have not been established. We conducted a pilot randomized trial of Mindfulness Coach (MC), a free, publicly available, trauma-informed mobile app tailored to veterans., Method: U.S. veterans with PTSD ( n = 173) were randomized to self-guided use of MC or waitlist control (WLC) with 8-week follow-up. Clinical outcomes were PTSD symptoms (PTSD Symptom Checklist-5), depression symptoms (Patient Health Questionnaire, nine item), and psychosocial functioning (Brief Inventory of Psychosocial Functioning). Primary analyses were intent-to-treat using linear mixed models with maximum likelihood estimation. App uptake, objective usage, and usability ratings measured acceptance and feasibility., Results: Participants varied in age, gender, and ethnoracial identity; most reported recent mental health care utilization. Although study attrition was high (68.4% overall) due to participant dropout (treatment: 43.0%; control: 43.7%) and technical study issues (23% overall), diagnostic tests showed no evidence of bias due to missingness. Study completers (MC: n = 19; WLC: n = 37) showed medium effects on PTSD symptoms ( b = -9.31, d = -0.69) and depression ( b = -3.10, d = -0.52). Higher-intensity users showed greater benefits. App engagement trended lower for women and minoritized subpopulations. No changes were observed in psychosocial functioning. Usability and helpfulness ratings were favorable., Conclusions: Transdiagnostic clinical benefits indicate promise for MC as a public health resource for veterans with PTSD. Further study is warranted to confirm these benefits and ensure consistent engagement across subpopulations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Live-ins: A mapping of relevant actors and moral norms at the public health level Abstract: Background: Live-ins are embedded in a network of multiple actors that shape their current working and living situation. The causes and effects of live-in arrangements go far beyond the actual care relationship and include structures and stakeholders that are interconnected at the Public Health level. Besides a legal responsibility, these actors also have a moral responsibility, which the article focuses on. Aim: The article provides an overview of relevant actors and moral norms in the context of live-ins at the public health level. Methods: The method followed the "Context and Actor Analysis". Actors at the public health level that are relevant for the live-ins' situation were identified, and the responsibilities and tasks presented in their websites as well as their respective target groups were collected. The ethical dimension was extracted from these self-descriptions. Results: The 23 actors address the live-ins directly or indirectly in their various social roles. The self-given tasks and the moral norms deduced from them, for which the actors are particularly responsible, illustrate the importance of justice and respect. Conclusions: The work provides the basis for an urgently needed empirical-ethical analysis on the current state of responsibility-taking. Not only the variety of the live-ins' roles, but also the multitude of actors involved and shared norms illustrate the necessity of close cooperation to be able to fulfil their responsibility.

Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: For several years, both the French Addictovigilance Network and French health authorities have consistently emphasized the need to provide opioid users with take-home naloxone (THN), the specific antidote for opioid overdoses. In March 2022, the French Health Authority recommended systematically assessing the appropriateness of prescribing THN to all opioid users, regardless of the context, and identified 8 high-risk situations. However, at present, THN distribution remains limited, particularly among primary care healthcare professionals. This study, conducted by the Pays de la Loire Centre for Evaluation and Information on Drug Dependence-Addictovigilance and supported by the Regional Health Agency, aims to explore healthcare professionals' practices and perceptions of these high-risk situations., Methods: An ad-hoc questionnaire was distributed via mail by the project's regional institutional partners to the target healthcare professionals: pharmacists, general practitioners (GPs), physicians practicing in specialities other than general medicine (SPs: algologists, psychiatrists and addictologists). It was completed online from 20/10/2022 to 30/12/2022., Results: Out of the 355 participants (158 pharmacists, 167 GPs and 30 SPs), nearly all were managing patients on opioids. In total, 47.7% of physicians and 27.8% of pharmacists reported experiencing difficulties in dealing with the risk of overdose when prescribing or dispensing opioids to their patients. In the 12months preceding the study, only 8 pharmacists and 34 physicians had prescribed/dispensed THN, primarily due to a lack of awareness of its existence (52% of pharmacists and 72% of physicians) and challenges in addressing the eight overdose risk situations listed by the HAS (ranging from 54% to 83% for all professionals). The best-trained healthcare professionals were those who prescribed the most THN (P<0.001)., Conclusion: The identification of barriers related to THN distribution in the regional SINFONI study, conducted among primary care healthcare professionals managing patients on opioids, highlights the need to develop a training tool specifically tailored for these professionals., (Copyright © 2024. Published by Elsevier Masson SAS.)

Endometrial carcinoma (EC) is the most frequent gynecological cancer, with an increasing incidence and mortality in recent times. The last decade has represented a true revolution with the development of the integrated histo-molecular classification of EC, which allows for the stratification of patients with morphologically indistinguishable disease into groups with different prognoses. Particularly, the POLE-mutated subgroup exhibits outstanding survival. Nevertheless, the indiscriminate application of molecular classification appears premature. Its prognostic significance has been proven mainly in endometrioid EC, the most common histotype, but it has yet to be convincingly confirmed in the other minor histotypes, which indeed account for a relevant proportion of EC mortality. Moreover, its daily use both requires a mindful pathologist who is able to correctly evaluate and unambiguously report immunohistochemical staining used as a surrogated diagnostic tool and is hampered by the unavailability of POLE mutation analysis. Further molecular characterization of ECs is needed to allow for the identification of better-tailored therapies in different settings, as well as the safe avoidance of surgery for fertility preservation. Hopefully, the numerous ongoing clinical trials in the adjuvant and metastatic settings of EC will likely produce evidence to refine the histo-molecular classification and therapeutic guidelines. Our review aims to retrace the origin and evolution of the molecular classification for EC, reveal its strengths and limitations, show clinical relevance, and uncover the desired future developments.

The emerging era of precision medicine is characterized by an increasing availability of targeted anticancer therapies and by the parallel development of techniques to obtain more refined molecular data, whose interpretation may not always be straightforward. Molecular tumor boards gather various professional figures, in order to leverage the analysis of molecular data and provide prognostic and predictive insights for clinicians. In addition to healthcare development, they could also become a tool to promote knowledge and research spreading. A growing body of evidence on the application of molecular tumor boards to clinical practice is forming and positive signals are emerging, although a certain degree of heterogeneity exists. This work analyzes molecular tumor boards' potential workflows, figures involved, data sources, sample matrices and eligible patients, as well as available evidence and learning examples. The emerging concept of multi-institutional, disease-specific molecular tumor boards is also considered by presenting two ongoing nationwide experiences., Competing Interests: Declaration of Competing Interest Giulia Buzzatti reports personal fees for consultancy/advisory role from Novartis, Eli Lilly and AstraZeneca. Umberto Malapelle reports personal fees for consultancy/advisory role from Boehringer Ingelheim, Roche, MSD, Amgen, ThermoFisher Scientific, Eli Lilly, Diaceutics, GlaxoSmithKline, Merck and AstraZeneca; personal fees for speakers’ bureau from Boehringer Ingelheim, AstraZeneca, Roche, MSD, Amgen, Merck, ThermoFisher Scientific, Eli Lilly, Diaceutics, GlaxoSmithKline and QIAGEN. Carmine De Angelis reports personal fees as consultant and/or speakers' bureau from Roche, Eli Lilly, GSK, Novartis, Pfizer, AstraZeneca, Gilead and Seagen; research grant to the Institution from Novartis. Maria Vittoria Dieci reports personal fees for consultancy/advisory role from Eli Lilly, Exact Sciences, Novartis, Pfizer, Seagen, Gilead, MSD, AstraZeneca, Daiichi Sankyo and Roche. Matteo Lambertini reports personal fees for advisory role from Roche, Eli Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences; speaker honoraria from Roche, Eli Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo and Takeda; travel grants from Gilead; research support (to the Institution) from Gilead. Angela Toss reports personal fees for consultancy/advisory role from Eli Lilly, Novartis, Pfizer, Seagen, Gilead, MSD, AstraZeneca and Daiichi Sankyo. Alberto Farolfi reports personal fees for consultancy/advisory role from AstraZeneca, GSK-Tesaro, Clovis and Janssen. Sandro Pignata reports speaker honoraria from AstraZeneca, Roche, PharmaMar, Tesaro, Pfizer and MSD; personal fees for consultancy/advisory role from AstraZeneca, Roche, PharmaMar, Pfizer, Tesaro and Clovis Oncology; research funding (to the Institution) from Roche, AstraZeneca, MSD and Pfizer. Michele Bartoletti reports personal fees for advisory board from GSK, MSD and EISAI; speaker fees from GSK and AstraZeneca; research grant from AstraZeneca and Roche; data monitoring committee for Novartis. Lorenzo Gerratana reports advisory/consultancy fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, MSD, Menarini Stemline, Abbvie; research funding from Menarini Silicon Biosystems; travel expenses from Menarini Stemline. Fabio Puglisi reports speaker honoraria from Roche, MSD, AstraZeneca, Novartis, Pierre Fabre, Daiichi Sankyo, Eisai, Eli Lilly, Pfizer and Exact Sciences; consulting or advisory role for Roche, Amgen, Novartis, Pfizer, Eisai, Seagen, Pierre Fabre, AstraZeneca/Daiichi Sankyo, Viatris, Eli Lilly, Gilead Sciences and Daiichi Sankyo Europe GmbH; research funding (to the Institution) from Eisai, AstraZeneca and Roche; travel and accommodation expenses fees from Roche, Celgene, GlaxoSmithKline, Amgen, AstraZeneca, MSD, Novartis, Eli Lilly and Pfizer. All reported potential conflicts of interest are outside the submitted work. All other authors have declared no potential conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Cancer rates are rising in low- and middle-income countries. While point-of-care ultrasound is now available globally and could serve to mitigate against this rise, its use in diagnosing cancers is inconsistent in lower-resourced healthcare contexts. This proof-of-concept study investigates the feasibility of an ultrasound training concept in a low-resource setting. It evaluates whether this educational concept led to improved knowledge and application of ultrasound diagnostics, cancer screening and staging and patient care., Material and Methods: The curriculum was developed through expert exchange and is based on the World Health Organisation's Manual of Diagnostic Ultrasound. It consisted of two didactic components: an on-site training phase across 5 days for a total of 24 hours, and a digital follow-up phase involving the meeting of a bi-weekly tumor board online. The learning objectives of the on-site training were normal imaging and recognition of common pathologies of the abdominal organs, vessels, lymph nodes, female breasts and lungs. The virtual tumour boards met to discuss cases and ultrasound findings, thus aiding continuing professional development after the training sessions had concluded. The face-to-face course component was accompanied by tests given before and after training as well as an evaluation sheet (Likert-scale with 1 = 'completely/very good' and 7 'not at all/very poor')., Results: Of 20 participants from a rural hospital in Tanzania, a total of 16 were included in the analysis (clinical officers n = 6; medical officers n = 10). A significant increase in knowledge ( p < 0.01) was measured both in the subjective self-assessment and in the theoretical competence tests. In multivariate linear regression, the status 'medical officers yes' ( β = 5.4; p = 0.04) had a significant influence on theory test results at T2. During the 24 virtual tumour board meetings, 28 cases were discussed and a continuous improvement in image acquisition quality was observed., Conclusion: The ultrasound education concept comes with a sustainable increase in clinical competence and improved oncological ultrasound screening locally. There is potential for the transfer of the concept to other locations, which can be explored in the future., Competing Interests: The authors declare no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Background and Aims: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries., Methods: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety., Results: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%)., Conclusions: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy., Methods: Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose-response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage., Results: Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity., Conclusions: Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM., (© 2024. The Author(s).)

PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer. Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations. The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations. In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue., (© 2024 British Neuropathological Society.)

Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aβ42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aβ when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity., (© 2024. The Author(s).)

Objective: Glucocorticoid resistance is a rare endocrine disease caused by variants of the NR3C1 gene encoding the glucocorticoid receptor (GR). We identified a novel heterozygous variant (GRR569Q) in a patient with uncommon reversible glucocorticoid resistance syndrome., Methods: We performed ex vivo functional characterization of the variant in patient fibroblasts and in vitro through transient transfection in undifferentiated HEK 293T cells to assess transcriptional activity, affinity, and nuclear translocation. We studied the impact of the variant on the tertiary structure of the ligand-binding domain through 3D modeling., Results: The patient presented initially with an adrenal adenoma with mild autonomous cortisol secretion and undetectable adrenocorticotropin hormone (ACTH) levels. Six months after surgery, biological investigations showed elevated cortisol and ACTH (urinary free cortisol 114 µg/24 h, ACTH 10.9 pmol/L) without clinical symptoms, evoking glucocorticoid resistance syndrome. Functional characterization of the GRR569Q showed decreased expression of target genes (in response to 100 nM cortisol: SGK1 control +97% vs patient +20%, P < .0001) and impaired nuclear translocation in patient fibroblasts compared to control. Similar observations were made in transiently transfected cells, but higher cortisol concentrations overcame glucocorticoid resistance. GRR569Q showed lower ligand affinity (Kd GRWT: 1.73 nM vs GRR569Q: 4.61 nM). Tertiary structure modeling suggested a loss of hydrogen bonds between H3 and the H1-H3 loop., Conclusion: This is the first description of a reversible glucocorticoid resistance syndrome with effective negative feedback on corticotroph cells regarding increased plasma cortisol concentrations due to the development of mild autonomous cortisol secretion., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement (AVR) for patients with moderate-to-high perioperative risk. Periprocedural TAVR complications decrease with growing expertise of implanters. Nevertheless, TAVR can still be accompanied by life-threatening adverse events such as intraprocedural cardiopulmonary resuscitation (CPR). This study analyzed the role of a reduced left-ventricular ejection fraction (LVEF) in intraprocedural complications during TAVR. Perioperative and postoperative outcomes from patients undergoing TAVR in a high-volume center (600 cases per year) were analyzed retrospectively with regard to their left-ventricular ejection fraction. Patients with a reduced left-ventricular ejection fraction (EF ≤ 40%) faced a significantly higher risk of perioperative adverse events. Within this cohort, patients were significantly more often in need of mechanical ventilation (35% vs. 19%). These patients also underwent CPR (17% vs. 5.8%), defibrillation due to ventricular fibrillation (13% vs. 5.4%), and heart-lung circulatory support (6.1% vs. 2.5%) more often. However, these intraprocedural adverse events showed no significant impact on postoperative outcomes regarding in-hospital mortality, stroke, or in-hospital stay. A reduced preprocedural LVEF is a risk factor for intraprocedural adverse events. With respect to this finding, the identified patient cohort should be treated with more caution to prevent intraprocedural incidents.

Depression is a chronic and debilitating mental disorder. Despite the existence of several evidence-based treatments, many individuals suffering from depression face myriad structural barriers to accessing timely care which may be alleviated by digital mental health interventions (DMHI). Accordingly, this randomized clinical trial (ClinicalTrials.gov: NCT04738084) investigated the efficacy of a newer version of the therapist-supported and guided DMHI, the Meru Health Program (MHP), which was recently enhanced with heart rate variability biofeedback and lengthened from 8- to 12-weeks duration, among people with elevated depression symptoms (N = 100, mean age 37). Recruited participants were randomized to the MHP (n = 54) or a waitlist control (n = 46) condition for 12 weeks. The MHP group had greater decreases in depression symptoms compared to the waitlist control (d = -0.8). A larger proportion of participants in the MHP group reported a minimal clinically important difference (MCID) in depression symptoms than participants in the waitlist control group (39.1 % vs. 9.8 %, χ 2 (1) = 9.90, p = .002). Similar effects were demonstrated for anxiety symptoms, quality of life, insomnia, and resilience. The results confirm the utility of the enhanced MHP in reducing depression symptoms and associated health burdens., Competing Interests: Declaration of competing interest Dr. Peiper reports research support from the National Institute of Mental Health (R44MH126836), Lilly Oncology, Gilead Sciences, and the Norton Healthcare Foundation. Drs. Peiper and Forman-Hoffman report stock options from Meru Health. Drs. Forman-Hoffman and Nelson were employed by Meru Health during the conduct of this research. They are now with Woebot Health and Verily Life Sciences, respectively. Dr. Peiper was employed by Meru Health; he continues to be at the Department of Epidemiology and Population Health, University of Louisville, Louisville, KY. Dr. Gould previously received funding from Meru Health, Inc., for an investigator-initiated study., (Published by Elsevier B.V.)

Objectives: To examine baseline factors (i.e., age, gender, mobile device proficiency, sensory impairment) associated with app engagement in a 12-week mental health app intervention and to explore whether app engagement predicts changes in depression and anxiety symptoms among middle-aged and older adults., Method: Mobile device proficiency, sensory impairment, depression, and anxiety symptoms were measured using questionnaires. App engagement was defined by metrics characterizing the core intervention features (i.e., messages sent to therapist, mindfulness meditation minutes, action tasks completed). Multiple regressions and multilevel models were conducted., Results: Forty-nine participants (M age = 57.40, SD = 11.09 years) enrolled. Women (β = .35, p < .05) and participants with less sensory impairment completed more action tasks (β = -.40, p < .05). Depressive and anxiety symptoms measured within the app declined significantly across treatment. Clinical significant improvements were observed for depression in 48.9% and for anxiety in 40% of participants. App engagement metrics were not predictive of depression or anxiety symptoms, either incrementally in time-lagged models or cumulatively in hierarchical linear regression analyses., Conclusion: App engagement is multifaceted; participants engaged differently by gender and ability. Participation in this digital mental health intervention reduced depression and anxiety symptoms, but these findings should be interpreted with caution as the study did not include a control condition. Our findings underscore the importance of considering individual factors that may influence use of a digital mental health intervention., (© 2023 Wiley Periodicals LLC.)

The cochlea forms a key element of the human auditory system in the temporal bone. Damage to the cochlea continues to produce significant impairment for sensory reception of environmental stimuli. To improve this impairment, the optical cochlear implant forms a new research approach. A prerequisite for this method is to understand how light propagation, as well as scattering, reflection, and absorption, takes place within the cochlea. We offer a method to study the light distribution in the human cochlea through phantom materials which have the objective to mimic the optical behavior of bone and Monte-Carlo simulations. The calculation of an angular distribution after scattering requires a phase function. Often approximate functions like Henyey-Greenstein, two-term Henyey-Greenstein or Legendre polynomial decompositions are used as phase function. An alternative is to exactly calculate a Mie distribution for each scattering event. This method provides a better fit to the data measured in this work., (© 2023 The Authors. Journal of Biophotonics published by Wiley‐VCH GmbH.)

Digital Mental Health Technologies (DMHTs) have the potential to close treatment gaps in settings where mental healthcare is scarce or even inaccessible. For this, DMHTs need to be affordable, evidence-based, justice-oriented, user-friendly, and embedded in a functioning digital infrastructure. This viewpoint discusses areas crucial for future developments of DMHTs. Drawing back on interdisciplinary scholarship, questions of health equity, consumer-, patient- and developer-oriented legislation, and requirements for successful implementation of technologies across the globe are discussed. Economic considerations and policy implications complement these aspects. We discuss the need for cultural adaptation specific to the context of use and point to several benefits as well as pitfalls of DMHTs for research and healthcare provision. Nonetheless, to circumvent technology-driven solutionism, the development and implementation of DMHTs require a holistic, multi-sectoral, and participatory approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kuhn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism., Objective: We aimed to analyze KDM1A gene sequence and KDM1A and GIPR expressions in somatotroph pituitary adenomas., Settings: We conducted a cohort study at university hospitals in France and in Italy. We collected pituitary adenoma specimens from acromegalic patients who had undergone pituitary surgery. We performed targeted exome sequencing (gene panel analysis) and array-comparative genomic hybridization on somatic DNA derived from adenomas and performed droplet digital PCR on adenoma samples to quantify KDM1A and GIPR expressions., Results: One hundred and forty-six patients with sporadic acromegaly were studied; 72.6% presented unsuppressed classical GH response, whereas 27.4% displayed a paradoxical rise in GH after oral glucose load. We did not identify any pathogenic variant in the KDM1A gene in the adenomas of these patients. However, we identified a recurrent 1p deletion encompassing the KDM1A locus in 29 adenomas and observed a higher prevalence of paradoxical GH rise (P = .0166), lower KDM1A expression (4.47 ± 2.49 vs 8.56 ± 5.62, P < .0001), and higher GIPR expression (1.09 ± 0.92 vs 0.43 ± 0.51, P = .0012) in adenomas from patients with KDM1A haploinsufficiency compared with those with 2 KDM1A copies., Conclusions and Relevance: Unlike in GIP-dependent primary bilateral macronodular adrenal hyperplasia, KDM1A genetic variations are not the cause of GIPR expression in somatotroph pituitary adenomas. Recurrent KDM1A haploinsufficiency, more frequently observed in GIPR-expressing adenomas, could be responsible for decreased KDM1A function resulting in transcriptional derepression on the GIPR locus., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although the availability of virtual care technologies in the Veterans Health Administration (VHA) continues to expand, ensuring engagement with these technologies among Veterans remains a challenge. VHA Health Services Research & Development convened a Virtual Care State of The Art (SOTA) conference in May 2022 to create a research agenda for improving virtual care access, engagement, and outcomes. This article reports findings from the Virtual Care SOTA engagement workgroup, which comprised fourteen VHA subject matter experts representing VHA clinical care, research, administration, and operations. Workgroup members reviewed current evidence on factors and strategies that may affect Veteran engagement with virtual care technologies and generated key questions to address evidence gaps. The workgroup agreed that although extensive literature exists on factors that affect Veteran engagement, more work is needed to identify effective strategies to increase and sustain engagement. Workgroup members identified key priorities for research on Veteran engagement with virtual care technologies through a series of breakout discussion groups and ranking exercises. The top three priorities were to (1) understand the Veteran journey from active service to VHA enrollment and beyond, and when and how virtual care technologies can best be introduced along that journey to maximize engagement and promote seamless care; (2) utilize the meaningful relationships in a Veteran's life, including family, friends, peers, and other informal or formal caregivers, to support Veteran adoption and sustained use of virtual care technologies; and (3) test promising strategies in meaningful combinations to promote Veteran adoption and/or sustained use of virtual care technologies. Research in these priority areas has the potential to help VHA refine strategies to improve virtual care user engagement, and by extension, outcomes., (© 2023. The Author(s).)

Objectives: In patients with left heart disease and severe aortic stenosis (AS), pulmonary hypertension (PH) is a common comorbidity and predictor of poor prognosis. Untreated AS aggravates PH leading to an increased right ventricular afterload and, in line to right ventricular dysfunction. The surgical benefit of aortic valve replacement (AVR) in elderly patients with severe AS and PH could be limited due to the multiple comorbidities and poor outcomes. Therefore, we purposed to investigate the impact of PH on short-term outcomes in patients with moderate to severe AS who underwent surgical AVR in our heart center., Methods: In this study we retrospectively analyzed a cohort of 99 patients with severe secondary post-capillary PH who underwent surgical AVR (AVR + PH group) at our heart center between 2010 and 2021 with a regard to perioperative outcomes. In order to investigate the impact of PH on short-term outcomes, the control group of 99 patients without pulmonary hypertension who underwent surgical AVR (AVR group) at our heart center with similar risk profile was accordingly analyzed regarding pre-, intra- and postoperative data., Results: Atrial fibrillation occurred significantly more often ( p = .013) in patients who suffered from PH undergoing AVR. In addition, the risk for cardiac surgery (EUROSCORE II) was significantly higher ( p < .001) in the above-mentioned group. Likewise, cardiopulmonary bypass time ( p = .018), aortic cross-clamp time ( p = .008) and average operation time ( p = .009) were significantly longer in the AVR + PH group. Furthermore, the in-hospital survival rate was significantly higher ( p = .044) in the AVR group compared to the AVR + PH group. Moreover, the dialysis rate was significantly higher ( p < .001) postoperatively in patients who suffered PH compared to the patients without PH undergoing AVR., Conclusion: In our study, patients with severe PH and severe symptomatic AS who underwent surgical aortic valve replacement showed adverse short-term outcomes compared to patients without PH., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Many patients in need for transcatheter aortic valve implantation (TAVI) present with an aortic annulus size larger than recommended by the manufacturer's instructions for use (IFU)., Aims: To investigate procedural and short-term safety and efficacy of TAVI in patients with extra-large annuli (ELA)., Methods: 30-day clinical outcome and valve performance as defined by VARC 3 of 144 patients with an aortic annulus size exceeding the permitted range were compared to a propensity-score matched control cohort of patients with an aortic annulus size consistent with the IFU., Results: Area and perimeter was 730.4 ± 53.9 mm 2 and 96.7 ± 6.5 mm in the ELA group. Technical (96.5% vs. 94.4%) and device success (82.3% vs. 84.5%) were comparable in patients with ELA (annulus area 730.4 ± 53.9 mm 2 ) and matched controls (annulus area 586.0 ± 48.2 mm 2 ). There was no significant difference in 30-day mortality rate, major intraprocedural complications, type 3 or 4 bleedings, major vascular complications, or stroke. Moderate paravalvular leakage (PVL) occurred more frequent in the ELA group (8.9% vs 2.2%; p = 0.02). The rate of new pacemaker implantation was 7.0% in the ELA cohort and 15.0% in the control cohort, respectively (p = 0.05)., Conclusion: Treatment of ELA patients with third-generation TAVI prostheses is feasible and safe, providing similar device success and complication rates as in matched controls with regular-sized aortic annulus. Post-interventional pacemaker implantation rates were low compared to the control group, yet incidence of moderate PVL remains problematic in ELA patients., (© 2023. The Author(s).)

Researchers at the Department of Veterans Affairs (VA) have studied interventions for posttraumatic stress disorder and co-occurring conditions in both traditional and digital formats. One such empirically supported intervention is web skills training in affective and interpersonal regulation (webSTAIR), a coached, 10-module web program based on STAIR. To understand which patient characteristics were predictive of webSTAIR outcomes in a sample of trauma-exposed veterans ( N = 189), we used machine learning (ML) to develop a prognostic index from among 18 baseline characteristics (i.e., demographic, military, trauma history, and clinical) to predict posttreatment posttraumatic stress disorder severity, depression severity, and psychosocial functioning impairment. We compared the ML models to a benchmark of linear regression models in which the only predictor was the baseline severity score of the outcome measure. The ML and "severity-only" models performed similarly, explaining 39%-45% of the variance in outcomes. This suggests that baseline symptom severity and functioning are strong indicators for webSTAIR outcomes in veterans, with higher severity indicating worse prognosis, and that the other variables examined did not contribute significant added predictive signal. Findings also highlight the importance of comparing ML models to an appropriate benchmark. Future research with larger samples could potentially detect smaller patient-level effects as well as effects driven by other types of variables (e.g., therapeutic process variables). As a transdiagnostic, digital intervention, webSTAIR can potentially serve a diverse veteran population with varying trauma histories and may be best conceptualized as a beneficial first step of a stepped care model for those with heightened symptoms or impairment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Toll-like receptor-driven and interleukin-1 (IL-1) receptor-driven inflammation mediated by IL-1 receptor-associated kinase 4 (IRAK4) is involved in the pathophysiology of hidradenitis suppurativa (HS) and atopic dermatitis (AD). KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics and clinical activity in patients with moderate to severe HS and in patients with moderate to severe AD. KT-474 was administered as a single dose and then daily for 14 d in 105 healthy volunteers (HVs), followed by dosing for 28 d in an open-label cohort of 21 patients. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of ≥93% at 600-1,600 mg and after 14 daily doses of ≥95% at 50-200 mg. In patients, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of patients with HS and patients with AD and was associated with improvement in skin lesions and symptoms. There were no drug-related infections. These results, from what, to our knowledge, is the first published clinical trial using a heterobifunctional degrader, provide initial proof of concept for KT-474 in HS and AD to be further confirmed in larger trials. ClinicalTrials.gov identifier: NCT04772885 ., (© 2023. The Author(s).)

Background: Coronary artery disease (CAD) is frequently diagnosed in patients with aortic valve stenosis. Treatment options include surgical and interventional approaches. We therefore analyzed short-term outcomes of patients undergoing either coronary artery bypass grafting with simultaneous aortic valve replacement (CABG + AVR) or staged percutaneous coronary intervention and transcatheter aortic valve implantation (PCI + TAVI)., Methods: From all patients treated since 2017, we retrospectively identified 237 patients undergoing TAVI within 6 months after PCI and 241 patients undergoing combined CABG + AVR surgery. Propensity score matching was performed, resulting in 101 matched pairs., Results: Patients in the CABG + AVR group were younger compared with patients in the PCI + TAVI group (71.9 ± 4.9 vs 81.4 ± 3.6 years; p  < 0.001). The overall mortality at 30 days before matching was higher after CABG + AVR than after PCI + TAVI (7.8 vs 2.1%; p  = 0.012). The paired cohort was balanced for both groups regarding demographic variables and the risk profile (age: 77.2 ± 3.7 vs78.5 ± 2.7 years; p  = 0.141) and EuroSCORE II (6.2 vs 7.6%; p  = 0.297). At 30 days, mortality was 4.9% in the CABG + AVR group and 1.0% in the PCI + TAVI group ( p  = 0.099). Rethoracotomy was necessary in 7.9% in the CABG + AVR, while conversion to open heart surgery was necessary in 2% in the PCI + TAVI group. The need for new pacemaker was lower after CABG + AVR than after PCI + TAVI (4.1 vs 6.9%; p  = 0.010). No paravalvular leak (PVL) was noted in the CABG + AVR group, while the incidence of moderate-to-severe PVL after PCI + TAVI was 4.9% ( p  = 0.027)., Conclusion: A staged interventional approach comprises a short-term survival advantage compared with combined surgery for management of CAD and aortic stenosis. However, PCI + TAVI show a significantly higher risk of atrioventricular block and PVL. Further long-term trials are warranted., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to compare postoperative outcomes and 30-day mortality in patients with reduced ejection fraction (<40%) who underwent isolated coronary artery bypass grafting (CABG) with (ONCAB) and without (OPCAB) the use of cardiopulmonary bypass., Methods: data from four university hospitals in Germany, spanning from January 2017 to December 2021, were retrospectively analyzed. A total of 551 patients were included in the study, and various demographic, intraoperative, and postoperative data were compared., Results: demographic parameters did not exhibit any differences. However, the OPCAB group displayed notably higher rates of preoperative renal insufficiency, urgent surgeries, and elevated EuroScore II and STS score. During surgery, the ONCAB group showed a significantly higher rate of complete revascularization, whereas the OPCAB group required fewer intraoperative transfusions. No disparities were observed in 30-day/in-hospital mortality for the entire cohort and the matched population between the two groups. Subsequent to surgery, the OPCAB group demonstrated significantly shorter mechanical ventilation times, reduced stays in the intensive care unit, and lower occurrences of ECLS therapy, acute kidney injury, delirium, and sepsis., Conclusions: the study's findings indicate that OPCAB surgery presents a safe and viable alternative, yielding improved postoperative outcomes in this specific patient population compared to ONCAB surgery. Despite comparable 30-day/in-hospital mortality rates, OPCAB patients enjoyed advantages such as decreased mechanical ventilation durations, shorter ICU stays, and reduced incidences of ECLS therapy, acute kidney injury, delirium, and sepsis. These results underscore the potential benefits of employing OPCAB as a treatment approach for patients with coronary heart disease and reduced ejection fraction.

Objective: Conduct a needs assessment to explore the experiences, barriers, and needs of genetic counselors (GCs), who counsel and refer young and metastatic breast cancer (BC) patients to support services, in order to develop resources to address any noticeable gaps., Methods: GCs providing care to BC patients were eligible to complete the survey. Support services were defined as resources to address patient-centered healthcare, emotional, and quality-of-life needs., Results: Most participants (n = 117) reported familiarity with cancer prevention services (93%); fewer were familiar with services secondary to a BC diagnosis (e.g., fatigue=16% and sexual health=24%). The volume of GCs indicating familiarity with support services increased significantly as work experience increased for seven services. Many (>50%) never referred patients to most (9/12) support services, excluding cancer prevention, mental health, and financial issues. Open-ended responses highlighted that GCs considered referrals to be outside their scope of practice or that healthcare systems prevent GCs from making referrals., Conclusion: GCs may benefit from curated resources and materials, especially for support services secondary to a BC diagnosis, to better support their patients., Practical Implications: Collaboration of GCs with other health professionals through integrative care programs may decrease burdens to accessing support services., Competing Interests: Declaration of Competing Interest Debra Duquette is a paid consultant for the Centers for Disease Control & Prevention, Division of Cancer Prevention & Control. She is also a paid member of the AIM Genetic Testing Panel. In 2022, Jennifer R. Klemp was employed by Caris Life Science, Inc; however this role did not impact this work. All other authors have no conflicts of interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Patients with coronary artery heart disease frequently suffer concomitant carotid vascular disease and are at high perioperative risk for neurological adverse events. Several concepts regarding the timing and modality of carotid revascularization are controversially discussed in patients with heart disease. Current guidelines recommendations on myocardial revascularization recommend a concomitant carotid endarterectomy (CEA) in patients with a history of stroke/transient ischemic attack (TIA) or 50-99% grade of the carotid stenosis. Our study aimed to analyze early outcome parameters of patients undergoing coronary artery bypass grafting (CABG), but also including concomitant heart valve surgery and simultaneous CEA., Methods: This study retrospectively analyzed a cohort of 111 patients from our institutional database undergoing heart surgery with CABG or heart-valve surgery between 2010 and 2020 with concomitant carotid surgery due to significant carotid stenosis., Results: Patients undergoing heart and simultaneous carotid surgery were 77 ± 8.0 years of age with a body mass index of 28 ± 1.7 kg/m 2 and a mean EuroSCORE II of 6.5 ± 2.3. Most patients (61%) had a smoking history and arterial hypertension (97%). The preoperative mean grade of internal carotid stenosis was 87 ± 4.2%, 13% of patients suffered from internal carotid artery stenosis on both sites. In total, 4.5% of patients had previously undergone internal carotid artery intervention before and 6.3% had a history of stroke with a persistent neurologic disorder in 1.8%, 8.9% of cases had prior TIA. Thirty-day all-cause mortality was 6.3% and postoperative neurologic events occurred with 7.2% TIA and 4.5% of disabling stroke., Conclusion: Within the reported patient population of coronary artery heart disease and significant internal carotid stenosis, a one-time approach with CABG or heart-valve surgery and CEA is safe and feasible as justified by clinical and neurological postoperative outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The coronavirus disease 2019 pandemic disrupted the practice of family-centered rounds. After the height of the pandemic, a trainee-led team identified a low percentage of bedside rounds on general pediatrics resident teams and combined a quality improvement framework and change management theory to increase bedside rounds. Initial efforts focused on a single general pediatrics team with the aim to increase bedside rounds from 18% to 50% within 6 months and sustain improvement for 12 months. A second aim was to increase bedside rounds from 7% to 50% for all general pediatrics resident teams within 6 months of spread., Methods: The Model for Improvement informed the identification of 3 primary drivers of bedside rounds: knowledge, culture, and logistics. Twelve plan-do-study-act (PDSA) cycles were implemented. Measures included the percentage of bedside rounds (primary outcome), caregiver attendance (secondary outcome), and nurse attendance and rounding time (balancing measures)., Results: For the initial team, 13 522 patient days were analyzed for the primary outcome with the average percentage of weekly bedside rounds increasing from 18% to 89% with 12 months of sustained improvement. The spread of the intervention to all teams revealed an increase in bedside rounding from 7% to 54%. The most significant improvements occurred after PDSA cycle 2, a communication bundle, and PDSA cycle 5, when the project was spread to all teams., Conclusions: This trainee-led initiative reveals the strength of the incorporation of change management theory within a quality improvement framework, resulting in rapid and sustainable increase in bedside rounds., (Copyright © 2023 by the American Academy of Pediatrics.)

One in four veteran primary care patients suffers from a mental health condition; however, most do not receive any treatment for these problems. Mobile health (mHealth) can overcome barriers to care access, but poor patient engagement limits the effectiveness and implementation of these tools. Peers may facilitate patient engagement with mHealth. We designed a protocol for peers to support implementation of mobile mental health tools in primary care and tested the feasibility, acceptability, and clinical utility of this approach. Thirty-nine patients across two Veterans Affairs sites who screened positive for depression during a primary care visit and were not currently in mental health treatment were enrolled. Participants were scheduled for four phone sessions with a peer over 8 weeks and introduced to five mobile apps for a range of transdiagnostic mental health issues (stress, low mood, sleep problems, anger, and trauma). Pre/post phone interviews using quantitative and qualitative approaches assessed participants' self-reported app use, satisfaction with the intervention, symptom change (stress, anxiety, depression, insomnia), and progress with personal health goals. On average, patients reported using 3.04 apps ( SD = 1.46). Per the Client Satisfaction Questionnaire, global satisfaction with the intervention was high ( M = 25.71 out of 32, SD = 3.95). Pre to post participants reported significant improvements in their level of stress, based on a quantitative measure ( p = .008), and 87% reported progress on at least one personal health goal. Findings support the feasibility, acceptability, and clinical utility of peer-supported mobile mental health for veterans in primary care. A randomized controlled trial of an adaptive version of this intervention is recommended. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: Mild or moderate liver cirrhosis increases the risk of complications after cardiac surgery. Ascites is the most common complication associated with liver cirrhosis. However, the prognostic value of ascites on postoperative morbidity and mortality after cardiac surgery remains uninvestigated., Methods: A retrospective study included 69 patients with preoperatively diagnosed liver cirrhosis who underwent cardiac surgery between January 2009 and January 2018 at the Department of Cardiothoracic Surgery, University Hospital of Cologne, Germany. The patients were divided into ascites and non-ascites groups based on preoperatively diagnosed ascites. Thirty-day mortality, postoperative complications, length of stay, and blood transfusions were analyzed postoperatively., Results: Out of the total of 69 patients, 14 (21%) had preoperatively diagnosed ascites. Ascites group had more postoperative complications such as blood transfusions (packed red blood cells: 78.6% vs. 40.0%, p = 0.010; fresh frozen plasma: 57.1% vs. 29.1%, p = 0.049), acute kidney injury (78.6% vs. 45.5%, p = 0.027), longer ICU stay (8 vs. 3 days, p = 0.044) with prolonged mechanical ventilation (57.1% vs. 23.6%, p = 0.015) and tracheotomy (28.6% vs. 3.6%, p = 0.003). The 30-day mortality rate was significantly higher in the ascites group than in the non-ascites group (35.7% vs. 5.5%, p = 0.002)., Conclusion: Ascites should be implemented in preoperative risk score assessments in cirrhotic patients undergoing cardiac surgery. Preoperative treatment of ascites could reduce the negative impact of ascites on postoperative complications after cardiac surgery. However, this needs to be thoroughly investigated in prospective randomized clinical trials., (© 2023. The Author(s).)

The tribological performance of novel bio-based lubricating greases thickened with electrospun lignin nanostructures was investigated in a nanotribometer using a steel-steel ball-on-disc configuration. The impact of electrospun nanofibrous network morphology on friction and wear is explored in this work. Different lignin nanostructures were obtained with electrospinning using ethylcellulose or PVP as co-spinning polymers and subsequently used as thickeners in castor oil at concentrations of 10-30% wt. Friction and wear generally increased with thickener concentration. However, friction and wear decreased when using homogeneous bead-free nanofiber mats (with higher fiber diameter and lower porosity) rather than nanostructures dominated by the presence of particles or beaded fibers, which was favored by reducing the lignin:co-spinning polymer ratio.

Objective: After transcatheter aortic valve implantation (TAVI), the optimal regimen of anticoagulant therapy in patients with an additional indication for oral anticoagulation remains a matter of debate. This study investigates the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients after TAVI in a real-world population., Methods: The German Aortic Valve RegistrY (GARY) is a prospective, multicentre registry enrolling patients undergoing invasive treatment for aortic valve disease. From January 2011 to December 2019, 1 41 790 patients from 92 hospitals in Germany were enrolled. Anticoagulatory treatment regimens were assessed at hospital discharge for patients after TAVI procedures. All-cause mortality and the combined endpoint 'cardiac and cerebrovascular events' containing myocardial infarction, stroke, transient ischaemic attack, aortic prosthesis reintervention and all-cause mortality in the first year after TAVI were examined by treatment regimen., Results: Of 45 598 patients (mean age 80.7±5.7 years, 49.3% males) undergoing TAVI, 16 974 patients (37.2%) received an anticoagulant regimen that included VKA or DOAC. Hereof, the majority of patients were prescribed VKA (n=11 333, 66.8%) compared with DOAC (n=5641, 33.2%) with an increase of DOAC use from 9.4% in 2011 to 69.9% in 2019. During the 1-year follow-up, the absolute event rates per 100 person-years for all-cause mortality and the combined endpoint cardiac and cerebrovascular events were 1.9 and 1.3 for VKA-treated and 1.7 and 1.2 for DOAC-treated patients, respectively. After adjustment for baseline confounders, all-cause mortality (HR 0.95, 95% CI 0.88 to 1.01, p=0.114) and cardiac and cerebrovascular event-free survival (HR 0.93, 95% CI 0.86 to 1.01, p=0.071) did not differ significantly between VKA and DOAC groups., Conclusions: This study supports evidence of the efficacy of DOAC use after TAVI in patients with an indication for oral anticoagulation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)