100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

Best practice standards for circular RNA research.

Circular RNAs (circRNAs) are formed in all domains of life and via different mechanisms. There has been an explosion in the number of circRNA papers in recent years; however, as a relatively young field, circRNA biology has an urgent need for common experimental standards for isolating, analyzing, expressing and depleting circRNAs. Here we propose a set of guidelines for circRNA studies based on the authors' experience. This Perspective will specifically address the major class of circRNAs in Eukarya that are generated by a spliceosome-catalyzed back-splicing event. We hope that the implementation of best practice principles for circRNA research will help move the field forward and allow a better functional understanding of this fascinating group of RNAs.

Linking Trauma Registry Patients With Insurance Claims: Creating a Longitudinal Patient Record.

INTRODUCTION: Trauma registries and their quality improvement programs only collect data from the acute hospital admission, and no additional information is captured once the patient is discharged. This lack of long-term data limits these programs' ability to affect change. The goal of this study was to create a longitudinal patient record by linking trauma registry data with third party payer claims data to allow the tracking of these patients after discharge. METHODS: Trauma quality collaborative data (2018-2019) was utilized. Inclusion criteria were patients age ≥18, ISS ≥5 and a length of stay ≥1 d. In-hospital deaths were excluded. A deterministic match was performed with insurance claims records based on the hospital name, date of birth, sex, and dates of service (±1 d). The effect of payer type, ZIP code, International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis specificity and exact dates of service on the match rate was analyzed. RESULTS: The overall match rate between these two patient record sources was 27.5%. There was a significantly higher match rate (42.8% versus 6.1%, P < 0.001) for patients with a payer that was contained in the insurance collaborative. In a subanalysis, exact dates of service did not substantially affect this match rate; however, specific International Classification of Diseases, Tenth Revision, Clinical Modification codes (i.e., all 7 characters) reduced this rate by almost half. CONCLUSIONS: We demonstrated the successful linkage of patient records in a trauma registry with their insurance claims. This will allow us to the collect longitudinal information so that we can follow these patients' long-term outcomes and subsequently improve their care.

Variation in Risk-Adjusted Ventilator-Associated Pneumonia Days Within a Quality Collaborative.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged mechanical ventilation, and longer intensive care unit stays. The rate of VAP (VAPs per 1000 ventilator days) within a hospital is an important quality metric. Despite adoption of preventative strategies, rates of VAP in injured patients remain high in trauma centers. Here, we report variation in risk-adjusted VAP rates within a statewide quality collaborative. METHODS: Using Michigan Trauma Quality Improvement Program data from 35 American College of Surgeons-verified Level I and Level II trauma centers between November 1, 2020 and January 31, 2023, a patient-level Poisson model was created to evaluate the risk-adjusted rate of VAP across institutions given the number of ventilator days, adjusting for injury severity, physiologic parameters, and comorbid conditions. Patient-level model results were summed to create center-level estimates. We performed observed-to-expected adjustments to calculate each center's risk-adjusted VAP days and flagged outliers as hospitals whose confidence intervals lay above or below the overall mean. RESULTS: We identified 538 VAP occurrences among a total of 33,038 ventilator days within the collaborative, with an overall mean of 16.3 VAPs per 1000 ventilator days. We found wide variation in risk-adjusted rates of VAP, ranging from 0 (0-8.9) to 33.0 (14.4-65.1) VAPs per 1000 d. Several hospitals were identified as high or low outliers. CONCLUSIONS: There exists significant variation in the rate of VAP among trauma centers. Investigation of practices and factors influencing the differences between low and high outlier institutions may yield information to reduce variation and improve outcomes.

Add-on testing: stability assessment of 63 biochemical analytes in centrifuged and capped samples stored at 16 °C.

OBJECTIVES: Integration of add-on testing in high-scale automated clinical laboratories constitute a valuable instrument not only for the clinicians and the general patient care, but also for the laboratory itself. Knowledge on sample quality and analytical stability upon storage is necessary to be able to offer add-on testing. The objectives of this study were to examine the analytical stability of 63 biochemical analytes in plasma and urine samples stored at 16 °C. METHODS: Samples were collected by professional laboratory technicians, analyzed at automated analyzers and stored in their primary, capped tube without separator for 10, 12, 16, 20 or 24 h at 16 °C. Stability was assessed by inspecting mean concentration of samples at baseline and examining if (A) mean concentration over time violated limits of bias, or if (B) individual sample concentrations violated limits of total error. RESULTS: The majority of the 63 analytes were stable for up to 24 h of storage. Few of the analytes were only suitable for add-on testing for 4, 6, 10, 12, 16 or 20 h of storage. One analyte, P-lactate dehydrogenase, was not found suitable for add-on testing when stored at 16 °C. CONCLUSIONS: Due to the increasing number of intelligent solutions for high-scale clinical laboratories, add-on testing has come to stay. Loss of stability could not be demonstrated for the majority of analytes after 10, 12, 16, 20 or 24 h of storage. This feature of analytical stability suggests that add-on testing is an acceptable tool for these analytes.

Ars2 and the Cap-Binding Complex Team up for Silencing.

In this issue, Sabin et al. (2009) and Gruber et al. (2009) reveal the protein Ars2 as a versatile regulator of RNA silencing. They show that Ars2 stimulates microRNA processing, contributes to antiviral resistance in flies, and is important for cell proliferation in mammals.

A window of opportunity for ICU end-of-life care-A retrospective multicenter cohort study.

BACKGROUND: The "window of opportunity" for intensive care staff to deliver end-of-life (EOL) care lies in the timeframe from "documenting the diagnosis of dying" to death. Diagnosing the dying can be a challenging task in the ICU. We aimed to describe the trajectories for dying patients in Danish intensive care units (ICUs) and to examine whether physicians document that patients are dying in time to perform EOL care and, if so, when a window of opportunity for EOL care exists. METHODS: From the Danish Intensive Care Database, we identified patients ≥18 years old admitted to Danish ICUs between January and December 2020 with an ICU stay of >96 h (four days) and who died during the ICU stay or within 7 days after ICU discharge. A chart review was performed on 250 consecutive patients admitted from January 1, 2020, to ICUs in the Central Denmark Region. RESULTS: In most charts (223 [89%]), it was documented that the patient was dying. Of those patients who received mechanical ventilation, 171 (68%) died after abrupt discontinuation of mechanical ventilation, and 63 (25%) died after gradual withdrawal. Patients whose mechanical ventilation was discontinued abruptly died after a median of 1 h (interquartile range [IQR]: 0-15) and 5 h (IQR: 2-15) after a diagnosis of dying was recorded. In contrast, patients with a gradual withdrawal died after a median of 108 h (IQR: 71-189) and 22 h (IQR: 5-67) after a diagnosis of dying was recorded. CONCLUSIONS: EOL care hinges on the ability to diagnose the dying. This study shows that there is a window of opportunity for EOL care, particularly for patients who are weaned from mechanical ventilation. This highlights the importance of intensifying efforts to address EOL care requirements for ICU patients and those discharged from ICUs who are not eligible for readmission.

How flash mobs can be used for data collection in healthcare? A scoping review protocol.

BACKGROUND: Traditional research methods often involve a lengthy process, but the emergence of flash mobs as an innovative data collection method offers the potential to gather substantial data within a short time frame. Flash mobs draw inspiration from the concept of large groups organizing through the internet or mobile devices to perform a prearranged action in public. In healthcare research, flash mobs serve as research organizing method to investigate clinically relevant questions on a large scale within a limited period. AIMS: This study aims to present a study protocol for a scoping review that comprehensively maps the existing literature on the use of flash mobs as a data collection method in healthcare research. METHODS: The review will follow established guidelines and include steps such as identifying the research question, identifying relevant studies, selecting studies, charting the data, and collating and summarizing the results. The review will utilize databases, manual screening of additional sources, and covidence for study selection and data charting. The findings will be summarized using descriptive statistics and a descriptive synthesis of qualitative data. The review protocol has been registered with the Open Science Framework. RESULTS: The results of this scoping review will provide insights into different flash mob designs, motivations, and the data collection process, contributing to the development of high-quality flash mob data collections in healthcare research.

Postextubation dysphagia management in Danish intensive care units: A national survey.

BACKGROUND: Postextubation dysphagia (PED) is a common complication to endotracheal intubation in critically ill patients and may lead to pneumonia, prolonged ventilation, longer hospital stays, and increased mortality. Recognizing dysphagia is paramount to preventing adverse events. The aim of this study was to describe PED management by investigating practice in Danish intensive care units (ICUs) focusing on current practice in 2023 (screening, prevention, and treatment), perceived best practice (barriers and facilitators), and when possible, to compare practice in 2017 and 2023. METHODS: Self-reported, cross-sectional survey of dysphagia practice in Danish ICUs administered from April to May 2023. In addition, data were compared with the 2017 Dysphagia in Intensive Care Evaluation study, when possible. RESULTS: Only half of Danish ICUs reported to have a PED protocol, and less than half routinely screen patients for dysphagia after extubation. Most common screening methods were the oral mechanism examination, water test, and Facio-oral tract therapy. Nurses and physicians often relied on an overall physical assessment of the patient. Best treatment methods were uniformly agreed to be patient positioning, modification of food and fluids, use of ergonomic utensils, and compensatory maneuvers. Key barriers to dysphagia management were lack of specialized staff, under-recognition of dysphagia as a health issue, and lack of standardized protocols. CONCLUSION: Awareness of PED is increasing and identification, prevention, and treatment is slowly improving, but systematic implementation of protocols for dysphagia screening and treatment could enhance dysphagia management in Danish ICUs.

The pathophysiology of estrogen in perinatal depression: conceptual update.

PURPOSE: Estrogen levels fall sharply after parturition and have long been considered an etiologic contributor to postpartum depression (PPD); however, no differences have been reported in plasma hormone concentrations in people who develop PPD. We examine the question: What is the current view of estrogen and the neurophysiologic processes it impacts in the development and treatment of PPD? METHODS: A literature review of the role of estrogen on candidate hormonal and epigenetic systems in the peripartum period was performed, including landmark historical studies and recent publications on estrogen-related research. The authors reviewed these papers and participated in reaching consensus on a conceptual framework of estrogen activity within the complexity of pregnancy physiology to examine its potential role for driving novel interventions. RESULTS: Estrogen fluctuations must be conceptualized in the context of multiple dramatic and interacting changes inherent in pregnancy and after birth, including progesterone, corticosteroids, inflammation, circadian biology and psychosocial challenges. Individuals who develop PPD have increased sensitivity to epigenetic alteration at estrogen-responsive genes, and these changes are highly predictive of PPD. An effective estrogen-based treatment for PPD has yet to be found, but interventions focused on associated inflammation and circadian rhythms are promising. CONCLUSIONS: Our understanding of the biological basis of PPD, one of the most common morbidities of the perinatal period, is expanding beyond changes in gynecologic hormone concentrations to include their impact on other systems. This growing understanding of the many processes influencing PPD will allow for the development of novel prevention and treatment strategies.

The role of health literacy in the association between social support and self-rated health: a Danish population-based study in 10,787 individuals with a long-term condition.

BACKGROUND: Managing a long-term condition requires higher health literacy. Social networks may play a crucial role for self-management. However, the pathway is not entirely understood. This study aimed to examine whether the association between social support and self-rated health is mediated by health literacy among individuals with a long-term condition. METHODS: This cross-sectional study used data from the "How are you?" 2021 survey in Central Denmark Region. Social support was assessed using a single question, health literacy with two dimensions from the Health Literacy Questionnaire (HLQ): 'Understanding health information' and 'Engaging with healthcare providers', and self-rated health with a single question from SF-36. Multiple logistic regression analyses were used to examine the associations, and multiple mediation analyses were performed using the Karlson-Holm-Breen method. RESULTS: A total of 10,787 individuals with a long-term condition were included in the study, whereas 6% (n = 595) reported a low level of social support. Both health literacy scales mediated the association between social support and self-rated health, particularly the ability to engage with healthcare providers, accounting for 25% of the variance. After adjustment for sociodemographic factors, individuals with a low level of social support had significantly higher odds of reporting difficulties in understanding health information (OR 2.53 (95% CI: 1.84-3.48)) and engaging with healthcare providers (OR 3.77 (95% CI: 2.96-4.79)). CONCLUSIONS: Health literacy, particularly the ability to engage with healthcare providers, was a mediator between social support and self-rated health. Additionally, a low level of social support was associated with higher odds of reporting lower health literacy. These findings suggest that strategies to enhance health literacy, improve health outcomes, and reduce health inequities may benefit from strengthening individuals' social network, particularly focusing on those with limited support.

Cosmetic Breast Augmentation with Autologous Ex Vivo-Expanded Adipose-Derived Mesenchymal Stem/Stromal Cell (Stemform®)-Enriched Fat Grafts: A Study of the First Twenty-Two Real-World Patients.

BACKGROUND: Fat grafting is commonly utilized in breast surgery, and since it was first described, clinicians and researchers have stridden towards improvement of graft retention. Current advancements include adding adipose-derived mesenchymal stem/stromal cells (MSC(AT)s), which have demonstrated promise for improved graft retention. OBJECTIVES: This study reports outcomes for the first twenty-two patients undergoing breast augmentation (Stemform BA) or artificial implant replacement (Stemform AIR) with MSC(AT)-enriched fat in a real-world setting. METHODS: Autologous MSC(AT)s were isolated and expanded ex vivo, then mixed with lipoaspirate and injected as enriched fat for Stemform BA and AIR. The breast volume was measured preoperatively and at 3 and 12 months postoperative using a 3D Infinity Dual-Lens Camera and LifeVizApp software. Additionally, independent plastic surgeons evaluated clinical images, and patient satisfaction was obtained at equal time points. RESULTS: Twenty-two patients were included. All completed 3 and 12 months clinical follow-up and 3 months volume measurements. Nineteen patients completed 12 months volume measurements. The median fat graft retention at 12 months was 95.7% (IQR = 82.44-103.12%) for Stemform BA patients and 113.0% (IQR = 94.8-131.2%) for Stemform AIR patients. The Stemform BA patients had a median breast enlargement of 172.0% (IQR = 156.7-241.0%). The implant replacement volume of Stemform AIR patients was 102% (IQR = 85.1-130.3%). The patient reported 92.8% and 100% would elect to repeat treatment if they had the opportunity for Stemform BA and Stemform AIR, respectively. CONCLUSION: Breast augmentation and breast implant replacement patients receiving ex vivo-expanded MSC(AT)-enriched fat grafts had high graft retention and patient satisfaction scores. The paper confirms the clinical efficacy of using ex vivo-expanded MSC(AT)s. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

What Matters to Patients on the Day of Surgery-A Flash Mob Study.

PURPOSE: To explore what matters to patients on the day of surgery, to describe how a flash mob study was conducted in a perioperative setting and to provide recommendations for future studies adopting the flash mob design. DESIGN: Flash mob study. METHODS: On June 6 to June 7, 2023, a 24-hour flash mob study was carried out in eight Danish perioperative units. Eligible for inclusion were adult patients scheduled for elective or acute surgery. After giving informed consent, patients answered two qualitative questions: what mattered to them on the day of surgery, and whether the staff were aware of this. Data were analyzed using content analysis. Patient characteristics were presented using descriptive statistics. FINDINGS: Patients expressed a need to feel safe and cared for, be informed, and to receive proper anesthesia and postoperative care. Twenty-nine percent had not told health care staff, most often because they had not been asked about what mattered to them and because they did not want to be a nuisance. CONCLUSIONS: The flash mob study was feasible and provided insight into patients' perspectives on the day of surgery. To gain insight into what matters on the day of surgery, health care professionals must actively ask patients. Furthermore, the flash mob proved to be an opportunity to create attention to what matters to patients on the day of surgery.

Nurse-led dysphagia screening in the intensive care unit - An implementation study.

BACKGROUND: Postextubation is common in the intensive care unit, and bedside screening by nurses is important to detect the condition and avoid aspiration to the airways. OBJECTIVE: The objective of this study was to assess the implementation of nurse-led, systematic dysphagia screening in the intensive care unit and to identify barriers and facilitators for dysphagia screening. METHODS: Design: pragmatic implementation study. Based on a programme theory, key behaviours were identified using the Behaviour Change Wheel framework. Implementation activities included education, e-learning, bedside peer support, feedback, and cues in the environment. Data sources included chart reviews, participant logs, implementation log and focus-group interviews. RESULTS: Participant logs showed 94% of nurses participated in educational sessions, less in e-learning (67%). Chart reviews showed very little use of nurse-led dysphagia screening. Only 19% of extubated patients followed screening protocol. Focus groups showed that nurses accepted the Yale Swallow Protocol as valid that new skills and understandings led to empowerment of nurses and aided decision making. Important barriers were keeping patients nil-per-mouth for intubation, lack of social support from other professionals, and difficulties with documentation. Facilitators were social support from colleagues. CONCLUSION: Implementation of nurse-led screening in intensive care was possible but challenged by external factors. Attention should be given to alterations of the screening protocol to avoid alteration of the instrument and easy documentation. Implementation of nurse-led dysphagia screening in intensive care may facilitate safe oral intake in patients and identify patients in need of specialised assessment. Implementation should aim to provide nurses with competences in screening patients swallowing function and allow contextualisation without altering the properties of the instrument.

Delirium and delirium severity screening in the intensive care-correspondence of screenings tools.

BACKGROUND: Delirium severity scores are gaining acceptance for measuring delirium in the intensive care unit (ICU). OBJECTIVE: The aim of this study was to evaluate the concordance between the Confusion Assessment Method for the intensive care unit (CAM-ICU)-7 and the Intensive Care Delirium Screening Checklist (ICDSC) as delirium severity measurement tools. METHODS: This was a prospective, comparative, observational multicentre study. This study was conducted in 18 Danish ICUs. Delirium was assessed in adult critically ill patients admitted to an ICU with a Richmond Agitation and Sedation Score (RASS) of -2 or above. ICU nurses assessed delirium with randomised paired delirium screening instruments, using the CAM-ICU, the ICDSC, and the CAM-ICU-7. The correlation between the CAM-ICU-7 and the ICDSC severity scores was evaluated for all predefined patient subgroups. RESULTS: A total of 1126 paired screenings were conducted by 127 ICU nurses in 850 patients. The patients' median age was 70 years (interquartile range: 61-77), 40% (339/850) were female, and 54% (457/850) had at least one positive delirium score. Delirium severity ranges (CAM-ICU-7: 0-7; and ICDSC: 0-8) were positively correlated (Pearson's correlation coefficient, r = 0.83; p < 0.0001). The overall agreement between the CAM-ICU-7 and the ICDSC for delirium measurement (CAM-ICU-7: >2, and ICDSC: >3) was substantial (kappa = 0.74), but the agreement decreased to fair (kappa = 0.38) if a patient had a RASS less than 0. CONCLUSIONS: The agreement between the CAM-ICU-7 and the ICDSC for delirium severity measurement was substantial but might be affected by the patient's sedation and agitation level at the time of assessment. IMPLICATIONS FOR PRACTICE: Both CAM-ICU-7 and ICDSC can be implemented for delirium severity measurement. Attention is warranted in both scores if a patient has a RASS of -2.

Defining dysphagia - a modified multi-professional Danish Delphi study.

OBJECTIVE: To establish a generally accepted Danish definition of dysphagia to enhance collaboration across sectors and professions. METHODS: The study was initiated by a multi-professional group of experienced researchers and board members of the Danish Society for Dysphagia. We used a modified Delphi methodology to achieve consensus among experienced health care professionals from different professions and contexts. The initial stage consisted of a literature search leading to the draft of different definitions followed by two Delphi rounds between professionals and a stakeholder consultation round. RESULTS: We conducted two Delphi rounds until one definition was clearly preferred. A total of 194 participants responded in round one, and 279 in round two. Both rounds had a broad representation of sectors and geography and most participants had worked with dysphagia for more than four years. CONCLUSION: The preferred definition was 'Dysphagia is a functional impairment that either prevents or limits the intake of food and fluids, and which makes swallowing unsafe, inefficient, uncomfortable or affects quality of life'. The definition was widely accepted among different health professional groups, patients and across sectors.

Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation.

INTRODUCTION: Donor lymphocyte infusion (DLI) is used to induce remission in patients who relapse after allogeneic stem cell transplantation (allo-HSCT). During the last decade, the hypomethylating agent Azacitidine has been used together with DLI for a synergistic graft-versus-leukemia (GVL) effect. Here we report results of DLI/Azacitidine treatment from a retrospective single-center study. METHODS: 50 AML/MDS patients treated for relapse after allo-HSCT between 2001 and 2020 with DLI at the Department of Hematology, at Rigshospitalet, Copenhagen University Hospital were included for analyses. A subgroup of patients who obtained complete remission (CR) after reinduction chemotherapy, received DLI in combination with low-dose (32 mg/m2) Azacitidine. RESULTS: Overall survival in all patients after DLI treatment was 59% at 2 years and 20% at 5 years. Relapse-free survival in patients in CR prior to DLI was 32% after 2 years and 7% after 5 years. In the DLI+low-dose-Azacitidine group, 5-years relapse-free survival was 40%. CONCLUSION: DLI remains an effective treatment in post-transplant relapse leaving one fifth of patients long-term survivors. Our results support the concomitant use of low-dose Azacitidine in the future use of DLI in order to enhance the GVL effect of donor lymphocytes.

Cardiac Characteristics of the First Two Waves of COVID-19 in Denmark and the Prognostic Value of Echocardiography: The ECHOVID-19 Study.

INTRODUCTION: COVID-19 has spread globally in waves, and Danish treatment guidelines have been updated following the first wave. We sought to investigate whether the prognostic values of echocardiographic parameters changed with updates in treatment guidelines and the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, 20E (EU1) and alpha (B.1.1.7), and further to compare cardiac parameters between patients from the first and second wave. METHODS: A total of 305 patients hospitalized with COVID-19 were prospectively included, 215 and 90 during the first and second wave, respectively. Treatment in the study was defined as treatment with remdesivir, dexamethasone, or both. Patients were assumed to be infected with the dominant SARS-CoV-2 variant at the time of their hospitalization. RESULTS: Mean age for the first versus second wave was 68.7 ± 13.6 versus 69.7 ± 15.8 years, and 55% versus 62% were males. Left ventricular (LV) systolic and diastolic function was worse in patients hospitalized during the second wave (LV ejection fraction [LVEF] for first vs. second wave = 58.5 ± 8.1% vs. 52.4 ± 10.6%, p < 0.001; and global longitudinal strain [GLS] = 16.4 ± 4.3% vs. 14.2 ± 4.3%, p < 0.001). In univariable Cox regressions, reduced LVEF (hazard ratio [HR] = 1.07 per 1% decrease, p = 0.002), GLS (HR = 1.21 per 1% decrease, p < 0.001), and tricuspid annular plane systolic excursion (HR = 1.18 per 1 mm decrease, p < 0.001) were associated with COVID-related mortality, but only GLS remained significant in fully adjusted analysis (HR = 1.14, p = 0.02). CONCLUSION: Reduced GLS was associated with COVID-related mortality independently of wave, treatment, and the SARS-CoV-2 variant. LV function was significantly impaired in patients hospitalized during the second wave.