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This article discusses the incidence and risk factors for malignancies in patients who have undergone heart transplantation at a single center. The study analyzed data from 296 patients who had undergone heart transplantation between September 2010 and August 2023. The overall incidence of malignancy was 8.8%, with skin cancer being the most common type. The study found that the switch to everolimus as part of the immunosuppression therapy did not reduce the incidence of malignancies. Early detection through close follow-up is important for improving the prognosis of these malignancies. [Extracted from the article]

Introduction: This study provides an update of survey-based data providing an overview of interventional electrophysiology over the last decade. Overall infrastructure, procedures, and training opportunities in Germany were assessed. Methods: By analyzing mandatory quality reports, German cardiology centres performing electrophysiological studies were identified to repeat a questionnaire from 2010 and 2015. Results: A complete questionnaire was returned by 192 centers performing about 75% of all ablations in Germany in 2020. In the presence of the COVID-19 pandemic, a total of 76.304 procedures including 68.407 ablations were reported representing a 38% increase compared to 2015. The median number of ablations increased from 180 in 2010 to 377 in 2020. AF was the most common arrhythmia ablated (51 vs. 35% in 2010). PVI with radiofrequency point-by-point ablation (64%) and cryo-balloon ablation (34%) were the preferred strategies. Less than 50 (75) PVI were performed by 31% (36%) of all centres. Only 25 and 24% of participating centres fulfilled EHRA and national requirements for training centre accreditation, respectively. There was a high number of EP centres with no fellows (38%). The proportion of female fellows in EP increased from 26% in 2010 to 33% in 2020. Conclusion: Comparing 2020, 2010 and 2015, an increasing number of EP centres and procedures were registered. In 2020, more than every second ablation was for therapy of AF. In the presence of an increasing number of procedures, training opportunities were still limited, and most centres did not fulfill recommended EHRA or national requirements for accreditation. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause development of cardiac allograft vasculopathy (CAV). Consequently, frequent monitoring and prophylaxes for CMV-DNAemia within the first weeks after HTx is regularly performed. However, CMV-DNAemia after termination of the perioperative prophylaxes is commonly observed. All adult patients undergoing HTx between September of 2010 and 2021 surviving the first 90 days (n=196) were retrospectively reviewed in September 2022. Patients were divided regarding the prevalence of CMV-DNAemia during the first postoperative year after termination of the institutional 90-day CMV prophylaxis. A total of n=35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (Controls, n=139). The remaining patients (n=22) were excluded due to incomplete data. CMV prophylaxis consisted of val-/ganciclovir as well as intravenous CMV immunoglobulin for high-risk D+/R- CMV IgG match. D+/R- and D-/R+ serology was significantly increased and D-/R- decreased in the CMV group (p<.01). In addition, mean age was 57.7±8.7 years but only 53.6±10.0 years for Controls (p=.03). Furthermore, ICU (p=.02) and total hospital stay (p=.03) after HTx was about 50% longer compared to the controls. Interestingly, incidence of CMV-DNAemia during the regular prophylaxis was only numerically increased in the CMV group (5.7% respectively.7%, p=.10), the same effect was also overserved for postoperative infective complications. Multivariate analyses could confirm that increased recipient age and D+/R- and D-/R+ CMV IgG match of donors and recipients were independent risk factors for post-prophylaxis CMV-DNAemia within the first year after heart transplantation. Our data should raise awareness for CMV-DNAemia after termination of regular prophylaxis schemes, as this affects one of five HTx patients and can contribute to the development of CAV. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk for late CMV-DNAemia. For these patients, prolongation or repetition of CMV prophylaxis including antiviral drugs and CMV immunoglobulins may be considered. [ABSTRACT FROM AUTHOR]

Aims: Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors. We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625)., Methods and Results: We enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired., Conclusion: In every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events., (© 2024. The Author(s).)

Background: The search for the best therapeutic approach in cardiopulmonary resuscitations (CPR) remains open to question. In this study, we evaluated if Amiodarone administration during CPR was associated with short-term mortality or neurological development. Methods: A total of 232 patients with sudden cardiac arrest (CA) with shockable rhythms were included in our analysis. Propensity score matching based on age, gender, type of CA, and CPR duration was used to stratify between patients with and without Amiodarone during CPR. Primary endpoints were short-term mortality (30-day) and neurological outcomes assessed by the cerebral performance category. Secondary endpoints were plasma lactate, phosphate levels at hospital admission, and the peak Neuron-specific enolase. Results: Propensity score matching was successful with a caliper size used for matching of 0.089 and a sample size of n = 82 per group. The 30-day mortality rates were similar between both groups ( p = 0.24). There were no significant differences in lactate levels at hospital admission and during the following five days between the groups. Patients receiving Amiodarone showed slightly higher phosphate levels at hospital admission, while the levels decreased to a similar value during the following days. Among CA survivors to hospital discharge, no differences between the proportion of good neurological outcomes were detected between the two groups ( p = 0.58), despite slightly higher peak neuron-specific enolase levels in CA patients receiving Amiodarone ( p = 0.03). Conclusions: Amiodarone administration is not associated with short-term mortality or neurological outcomes in CA patients with shockable rhythms receiving CPR.

Background: In Europe, more than 300,000 persons per year experience out-of-hospital cardiac arrest (OHCA). Despite medical progress, only few patients survive with good neurological outcome. For many issues, evidence from randomized trials is scarce. OHCA often occurs for cardiac causes. Therefore, we established the national, prospective, multicentre German Cardiac Arrest Registry (G-CAR). Herein, we describe the first results of the pilot phase., Results: Over a period of 16 months, 15 centres included 559 consecutive OHCA patients aged ≥ 18 years. The median age of the patients was 66 years (interquartile range 57;75). Layperson resuscitation was performed in 60.5% of all OHCA cases which were not observed by emergency medical services. The initial rhythm was shockable in 46.4%, and 29.1% of patients had ongoing CPR on hospital admission. Main presumed causes of OHCA were acute coronary syndromes (ACS) and/or cardiogenic shock in 54.8%, with ST-elevation myocardial infarction being the most common aetiology (34.6%). In total, 62.9% of the patients underwent coronary angiography; percutaneous coronary intervention (PCI) was performed in 61.4%. Targeted temperature management was performed in 44.5%. Overall in-hospital mortality was 70.5%, with anoxic brain damage being the main presumed cause of death (38.8%). Extracorporeal cardiopulmonary resuscitation (eCPR) was performed in 11.0%. In these patients, the in-hospital mortality rate was 85.2%., Conclusions: G-CAR is a multicentre German registry for adult OHCA patients with a focus on cardiac and interventional treatment aspects. The results of the 16-month pilot phase are shown herein. In parallel with further analyses, scaling up of G-CAR to a national level is envisaged. Trial registration ClinicalTrials.gov identifier: NCT05142124., (© 2024. The Author(s).)

Streptococcus pneumoniae is a leading cause of morbidity and mortality in children and older adults. Yet knowledge on the development of pneumococcal protein-specific antibody responses throughout life is limited. To investigate this, we measured serum IgG levels to 55 pneumococcal proteins in 11-month old infants (n=73), 24-month old children (n=101), parents (n=99), adults without children <6 years of age (n= 99) and older adults aged >60 years (n=100). Our findings revealed low IgG levels in infancy, with distinct development patterns peaking in adults. A decrease in levels was observed for 27 antigens towards older age. Adults and older adults had increased IgG levels during pneumococcal carriage and at increased exposure risk to S. pneumoniae. Carriage was a stronger predictor than exposure or age for antibody responses. These findings highlight the dynamic nature of naturally acquired humoral immunity to pneumococcal proteins throughout life, offering insights for age-targeted interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Streptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Paulikat, Schwudke, Hammerschmidt and Voß.)

Background: The rarity of childhood interstitial lung disease (chILD) makes it challenging to conduct powered trials. In the InPedILD trial, among 39 children and adolescents with fibrosing ILD, there was a numerical benefit of nintedanib versus placebo on change in forced vital capacity (FVC) over 24 weeks (difference in mean change in FVC % predicted of 1.21 [95% confidence interval: -3.40, 5.81]). Nintedanib has shown a consistent effect on FVC across populations of adults with different diagnoses of fibrosing ILD., Methods: In a Bayesian dynamic borrowing analysis, prespecified before data unblinding, we incorporated data on the effect of nintedanib in adults and the data from the InPedILD trial to estimate the effect of nintedanib on FVC in children and adolescents with fibrosing ILD. The data from adults were represented as a meta-analytic predictive (MAP) prior distribution with mean 1.69 (95% credible interval: 0.49, 3.08). The adult data were weighted according to expert judgment on their relevance to the efficacy of nintedanib in chILD, obtained in a formal elicitation exercise., Results: Combined data from the MAP prior and InPedILD trial analyzed within the Bayesian framework resulted in a median difference between nintedanib and placebo in change in FVC % predicted at Week 24 of 1.63 (95% credible interval: -0.69, 3.40). The posterior probability for superiority of nintedanib versus placebo was 95.5%, reaching the predefined success criterion of at least 90%., Conclusion: These findings, together with the safety data from the InPedILD trial, support the use of nintedanib in children and adolescents with fibrosing ILDs., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Percutaneous left ventricular assist devices (pVADs) may be used in patients with cardiogenic shock (CS) to stabilize hemodynamics and maintain sufficient end-organ perfusion. Vascular complications are commonly observed in patients with pVAD support. We aimed to assess the relationship between pVAD implantation time and access-site complication rates. This retrospective observational study included all patients who underwent pVAD insertion for the treatment of CS at our university hospital between 2014 and 2021 (n = 224). Depending on the pVAD insertion time, the patients were assigned to the on-hours (n = 120) or off-hours group (n = 104). Both groups had comparable baseline characteristics and comorbidities. The rate of access-site-related complications was higher in the off-hours group than in the on-hours group (26% vs. 10%, p = 0.002). Premature discontinuation of pVAD support to prevent limb ischemia or manage access-site bleeding was required more often in the off-hours group than in the on-hours group (14% vs. 5%, p = 0.016). Pre-existing peripheral artery disease and implantation time off-hours were independent predictors for access-siterelated vascular complications. In conclusion, patients with CS in whom pVAD was inserted during off-hours had higher rates of access-site-related complications and premature discontinuation of pVAD support than those in whom pVAD was inserted during on-hours., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: Out-of-hospital cardiac arrest (OHCA) remains a frequent medical emergency with low survival rates even after a return of spontaneous circulation (ROSC). Growing evidence supports formation of dedicated teams in scenarios like cardiogenic shock to improve prognosis. Thus, the European Resuscitation Council (ERC) recommended introduction of Cardiac Arrest Centers (CAC) in their 2015 guidelines. Here, we aimed to elucidate the effects of newly introduced CACs in Germany regarding survival rate and neurological outcome., Methods: A multicenter retrospective observational cohort study was performed at three university hospitals and outcomes after OHCA were compared before and after CAC accreditation. Primary outcomes were survival until discharge and favorable neurological status (CPC 1 or 2) at discharge., Results: In total 784 patients (368 before and 416 after CAC accreditation) were analyzed. Rates of immediate percutaneous coronary intervention (40 vs. 52%, p = 0.01) and implementation of extracorporeal CPR (8 vs. 13%, p < 0.05) increased after CAC accreditation. Likelihood of favorable neurological status at discharge was higher after CAC accreditation (71 vs. 87%, p < 0.01), whereas overall survival remained similar (35 vs. 35%, p > 0.99)., Conclusion: CAC accreditation is linked to higher rates of favorable neurological outcome and unchanged overall survival., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘R.W. is employed at Abiomed Inc., Danvers, USA as medical officer. All other authors: none. B.W.B. is member of the editorial board of Resuscitation’., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objective: Surrogate endpoints enable determination of meaningful treatment effects more efficiently than applying the endpoint of ultimate interest. We used data from trials of nintedanib in subjects with pulmonary fibrosis to assess decline in forced vital capacity (FVC) as a surrogate for mortality., Methods: Data from the nintedanib and placebo groups of trials in subjects with idiopathic pulmonary fibrosis, other forms of progressive pulmonary fibrosis, and pulmonary fibrosis due to systemic sclerosis (NCT00514683, NCT01335464, NCT01335477, NCT01979952, NCT02999178, NCT02597933) were pooled. Using joint models for longitudinal and time-to-event data, we assessed the association between decline in FVC % predicted and time to death over 52 weeks. The rate of change in FVC % predicted and the current value of FVC % predicted were modelled longitudinally and estimates applied as predictors in time-to-event models., Results: Among 2583 subjects with pulmonary fibrosis, both a greater rate of decline in FVC % predicted and a lower current value of FVC % predicted were associated with an increased risk of death over 52 weeks (HR 1.79 [95% CI: 1.57, 2.03] and HR 1.24 [1.17, 1.32] per 5-percentage point decrease, respectively). Associations between the rate of change in FVC % predicted and the risk of death were consistent between patients with IPF and other ILDs., Conclusion: Data from clinical trials in subjects with pulmonary fibrosis of diverse aetiology demonstrate a strong association between decline in FVC % predicted and mortality over 52 weeks, supporting FVC decline as a surrogate for mortality in these patients., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause cardiac allograft vasculopathy. Consequently, monitoring and prophylaxis for cytomegalovirus deoxyribonucleic acid (CMV-DNAemia) within the first weeks after HTx is recommended., Methods: All patients who underwent HTx between September 2010 and 2021 surviving the first 90 days (n = 196) were retrospectively reviewed. The patients were divided on the prevalence of CMV-DNAemia during the first postoperative year after the end of the prophylaxis. A total of n = 35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (controls, n = 139). The remaining patients (n = 22) were excluded due to incomplete data., Results: Positive donors and negative recipients (D+/R-) and negative donors and positive recipients (D-/R+) serology was significantly increased and D-/R- decreased in the CMV group (p < .01). Furthermore, the mean age was 57.7 ± 8.7 years but only 53.6 ± 10.0 years for controls (p = .03). Additionally, the intensive care unit (p = .02) and total hospital stay (p = .03) after HTx were approximately 50% longer. Interestingly, the incidence of CMV-DNAemia during prophylaxis was only numerically increased in the CMV group (5.7%, respectively, 0.7%, p = .10), the same effect was also observed for postoperative infections. Multivariate analyses confirmed that D+/R- and D-/R+ CMV immunoglobulin G match were independent risk factors for postprophylaxis CMV-DNAemia., Conclusion: Our data should raise awareness of CMV-DNAemia after the termination of regular prophylaxis, as this affects one in five HTx patients. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk of late CMV-DNAemia. For these patients, prolongation, or repetition of CMV prophylaxis, including antiviral drugs and CMV immunoglobulins, may be considered., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD)., Methods and Analysis: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, stratified by background nintedanib use. Patients must be diagnosed with pulmonary fibrosis other than IPF that is progressive, based on predefined criteria. Patients must have forced vital capacity (FVC) ≥45% predicted and haemoglobin-corrected diffusing capacity of the lung for carbon monoxide ≥25% predicted. Patients must be receiving nintedanib for at least 12 weeks, or not receiving nintedanib for at least 8 weeks, prior to screening. Patients on stable treatment with permitted immunosuppressives (eg, methotrexate, azathioprine) may continue their treatment throughout the trial. Patients with clinically significant airway obstruction or other pulmonary abnormalities, and those using immunosuppressives that may confound FVC results (cyclophosphamide, tocilizumab, mycophenolate, rituximab) or high-dose steroids will be excluded. The primary endpoint is absolute change from baseline in FVC (mL) at week 52. The key secondary endpoint is time to the first occurrence of any acute ILD exacerbation, hospitalisation for respiratory cause or death, over the duration of the trial., Ethics and Dissemination: The trial is being carried out in accordance with the ethical principles of the Declaration of Helsinki, the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The study results will be disseminated at scientific congresses and in peer-reviewed publications., Trial Registration Number: NCT05321082., Competing Interests: Competing interests: TM has received consulting fees from Boehringer Ingelheim, Roche/Genentech, AstraZeneca, Bayer, Blade Therapeutics, Bristol Myers Squibb, Galapagos, Galecto, GSK, IQVIA, Pliant Therapeutics, Respivant, Theravance and Veracyte. He has also received speaker fees from Boehringer Ingelheim and Roche/Genentech. SA has received research grants from Boehringer Ingelheim, Momenta and Janssen; consulting fees from Boehringer Ingelheim, Novartis, AbbVie, CSL Behring, AstraZeneca and aTyr Pharma. AA has received research grants and speaker fees from Boehringer Ingelheim and Taiho Pharm. Co.; and been an advisory committee member for Boehringer Ingelheim, Taiho Pharm. Co., Toray Medical Co. and Kyorin Pharm. Co. VC has received unrestricted grants from Boehringer Ingelheim; consulting fees from AstraZeneca, Boehringer Ingelheim, Celgene/BMS, CSL Behring, Ferrer, Galapagos, Pliant, PureTech, RedX, Roche, Sanofi and Shionogi; lecture fees from Boehringer Ingelheim and Roche; support for attending meetings from Boehringer Ingelheim and Hoffmann-La Roche; has participated in data and safety monitoring boards for Galapagos, Galecto and Roche; and been on an adjudication committee for FibroGen. A-MH-V has received grant/research support from Boehringer Ingelheim and Janssen; consulting fees from Boehringer Ingelheim, Jannsen, ARXX, Medscape, Roche and Actelion; speaker honoraria from Boehringer Ingelheim, ARXX, Janssen, Lilly, Medscape, Merck Sharp & Dohme, Roche and Actelion. MK is an advisor or review panel member for Boehringer Ingelheim, Galapagos and Roche; and has received consultancy fees, grants and speaker fees from Boehringer Ingelheim and Roche. JMO has received consultancy fees and grants from Boehringer Ingelheim, and consultancy fees from Roche/Genentech and Lupin Pharmaceuticals. LR has received research grants from Boehringer Ingelheim and the Italian Medicine Agency; been an advisory board member for Roche, Boehringer Ingelheim, FibroGen and Promedior; been involved in consulting activity for Biogen, Celgene, Nitto, Pliant Therapeutics, Toray, Bristol Myers Squibb, Respivant and CSL Behring; received payment for lectures from Boehringer Ingelheim, Zambon and Cipla; received support for attending meetings from Boehringer Ingelheim and Roche; and been a steering committee member for Boehringer Ingelheim and Roche. CV has received personal fees from Boehringer Ingelheim, Roche and Bristol Myers Squibb; and support for attending meetings from Boehringer Ingelheim and Roche. MSW has received grants from AstraZeneca-Daiichi, Boehringer Ingelheim, Hoffman-La Roche, The Netherlands Organisation for Health Research and Development, The Dutch Lung Foundation and The Dutch Pulmonary Society; consulting fees from Boehringer Ingelheim, Galapagos, Bristol Myers Squibb, Galecto, Respivant and NeRRe Therapeutics, Horizon Therapeutics, PureTech Health, Kinevant Sciences, Molecure, CSL Behring, Thyron and Vicore; speaker fees from Boehringer Ingelheim, Galapogas, Hoffman-La Roche, Novartis and CSL Behring; support for attending meetings from Boehringer Ingelheim, Galapagos and Hoffman-La Roche; has participated in advisory boards for Savara, Galapagos and Dutch lung fibrosis and sarcoidosis patient associations (unpaid); and has held leadership roles as chair of the Idiopathic Interstitial Pneumonia group of the European Respiratory Society, member of the board of the Netherlands Respiratory Society, member of the scientific advisory board of the European Idiopathic Pulmonary Fibrosis and Related Disorders Federation and chair of the educational committee of the European Reference Network for Rare Lung Diseases. All grants and fees were paid to her institution. CC, CS, FV and DW are employees of Boehringer Ingelheim. FJM has served on a steering committee, advisory board, data safety monitoring board or adjudication committee for Afferent/Merck, Bayer, Biogen, Boehringer Ingelheim, Nitto, Respivant, Roche and Veracyte; and has received consulting fees or payment for presentations from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Bridge Biotherapeutics, CSL Behring, DevPro, IQVIA, Roche/Genentech, Sanofi, Shionogi, twoXAR, United Therapeutics and Veracyte., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : Loss of functional capacity is one of the hallmarks in cardiovascular aging. Cocoa flavanols (CF) exert favorable effects on endothelial function, blood pressure, and inflammation. These cardiovascular health markers worsen with increasing age and limit functional exercise capacity. Aim : To investigate the effect of CF on cardiorespiratory-fitness in healthy elderly people. Methods : In a randomized, double-masked, placebo-controlled, parallel-group dietary intervention trial, 68 healthy elderly people (55-79 years, 28 female) received either 500 mg of CF or a nutrient-matched control capsule twice a day for 30 days. Primary endpoint was defined as peak oxygen consumption (VO 2 ) in a cardiopulmonary exercise test (CPET). Secondary endpoints were oxygen pulse (VO 2 per heart rate (HR)), resting blood pressure (BP), and resting vascular function. Results : After 30 days of CF intake peakVO 2 increased by 190 ml min -1 (95% CI 1-371 ml min -1 ) and peakVO 2 per kg by 2.5 ml (min kg) -1 (95% CI 0.30-4.2 ml (min kg) -1 ). O 2 -pulse increased by 1.7 ml (95% CI 0.29-3.2 ml) and max exercise capacity by 9.6 W (95% CI 2.1-17.7 W). CF decreased resting systolic and diastolic BP by 5.4 mmHg (95% CI -10.7 to -0.1 mmHg) and 2.9 mmHg (95% CI -5.5 to -0.4 mmHg), respectively. Flow-mediated vasodilation (FMD) increased by an absolute 1.3% (95% CI 0.76-1.79%) in the CF group. Indexes of pulmonary function were not affected. No changes for primary and secondary endpoints were detected in control. Conclusion : CF substantially improve markers of cardiorespiratory fitness in healthy elderly humans highlighting their potential to preserve cardiovascular health with increasing age.

Preterm infants are at an increased health risk due to their low maturity. To monitor their health, vital signs are measured using contact-based methods. The adhesive sensors used to detect body temperature can damage the sensitive skin of neonates. Thus, a subject of current research is non-invasive measurement methods based on infrared thermography. In this context, thermal phantoms can be used to develop contactless temperature measurement systems and, furthermore, investigate the thermal behavior of preterm infants. In this work, an improved thermal phantom is introduced to simulate the thermoregulation of a premature infant. The shape and size are adapted to the body of a premature infant in the 29th week of pregnancy. The phantom consists of a 3D-printed frame to which carbon fiber heating elements and Pt1000 temperature sensors are attached. The frame is enclosed by a thermally conductive skin layer made of a silicone boron nitride mixture. Ball joints allow the body parts to tilt and rotate, enabling the phantom to model different body postures. Using PI controllers, the thermal phantom can achieve desired temperatures in 13 different areas of the body while maintaining a homogeneous temperature distribution on the skin surface. In addition, pathological temperature scenarios such as a central-peripheral temperature difference or a change in body temperature can be simulated with a maximum deviation of ± 0.4 °C.

Aims: Identifying patients who may benefit from mechanical circulatory support (MCS) after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) remains challenging; thus, a search for helpful biomarkers is warranted. We aimed to evaluate phosphate and lactate levels on admission regarding their associations with survival with and without MCS., Methods: In 224 OHCA patients who achieved ROSC, the initial phosphate and lactate levels were investigated to discriminate in-hospital mortality by receiver operating characteristic (ROC) curves. According to the Youden Index (YI) from the respective ROC, the groups were risk stratified by both biomarkers, and 30-day mortality was analyzed in patients with and without MCS., Results: Within the entire collective, MCS was not associated with a better chance of survival. Both phosphate and lactate level elevations showed good yet comparable discriminations to predict mortality (areas under the curve: 0.80 vs. 0.79, p = 0.74). In patients with initial phosphate values > 2.2 mmol/L (>YI), 30-day mortality within the MCS cohort was lower (HR 2.3, 95% CI: 1.4-3.7; p = 0.0037). In patients with lower phosphate levels and groups stratified by lactate, 30-day mortality was similar in patients with and without MCS., Conclusions: We found a significant association between survival and MCS therapy in patients with phosphate levels above 2.2 mmol/L (Youden Index), and a similar discrimination of patient overall survival by lactate and phosphate. Prospective studies should assess the possible independent prognostic value of phosphate and its clearance for MCS efficiency.

Background: Monitoring the body temperature of premature infants is vital, as it allows optimal temperature control and may provide early warning signs for severe diseases such as sepsis. Thermography may be a non-contact and wireless alternative to state-of-the-art, cable-based methods. For monitoring use in clinical practice, automatic segmentation of the different body regions is necessary due to the movement of the infant., Methods: This work presents and evaluates algorithms for automatic segmentation of infant body parts using deep learning methods. Based on a U-Net architecture, three neural networks were developed and compared. While the first two only used one imaging modality (visible light or thermography), the third applied a feature fusion of both. For training and evaluation, a dataset containing 600 visible light and 600 thermography images from 20 recordings of infants was created and manually labeled. In addition, we used transfer learning on publicly available datasets of adults in combination with data augmentation to improve the segmentation results., Results: Individual optimization of the three deep learning models revealed that transfer learning and data augmentation improved segmentation regardless of the imaging modality. The fusion model achieved the best results during the final evaluation with a mean Intersection-over-Union (mIoU) of 0.85, closely followed by the RGB model. Only the thermography model achieved a lower accuracy (mIoU of 0.75). The results of the individual classes showed that all body parts were well-segmented, only the accuracy on the torso is inferior since the models struggle when only small areas of the skin are visible., Conclusion: The presented multi-modal neural networks represent a new approach to the problem of infant body segmentation with limited available data. Robust results were obtained by applying feature fusion, cross-modality transfer learning and classical augmentation strategies., (© 2023. The Author(s).)

In patients after mechanical heart valve replacement anticoagulation is required for the prevention of thrombotic and thromboembolic events. In this setting oral anticoagulation can only be performed with vitamin K antagonists (VKA), while currently all available non-vitamin K dependent oral anticoagulants (NOAC) are contraindicated in patients with mechanical heart valve replacement. This review deals with anticoagulation in patients with mechanical heart valve replacement as well as coagulation inhibition after bioprosthetic or percutaneous valve replacement. In addition, recommendations are given for antithrombotic medication in patients with mechanical heart valve replacement in various clinical scenarios., (© 2021. Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

Purpose: Although a moderate proportion of cardiac arrest (CA) patients achieve a return of spontaneous circulation (ROSC), few survive to discharge, mostly with poor neurological development. As serum phosphate levels were described as elevated after cardiopulmonary resuscitation (CPR), we asked whether these elevations would predict a higher risk of mortality and impaired neurological outcome in CA patients following ROSC. Methods: Initial serum phosphate levels, survival, and neurologic status at discharge of 488 non-traumatic CA patients treated at a single German hospital after achieving ROSC were analyzed. The cut-off value of phosphate for mortality prediction was determined using the receiver operator characteristic (ROC) curve, and patients were divided accordingly for comparison. Results were validated by analyzing phosphate levels in a multi-centric cohort containing 3299 CA patients from the eICU database of the United States. Results: In the German cohort, ROC analysis showed a 90% specificity for phosphate levels >2.7 mmol/L to predict mortality (AUC: 0.76, p < 0.0001), and phosphate level elevations were associated with higher in-hospital mortality (crude odds ratio 3.04, 95% CI 2.32 to 4.08). Patients with initial phosphate levels >2.7 mmol/L had significantly higher mortality in both analyzed collectives ( p < 0.0001). Similarly, patients from the German cohort who initially had higher phosphate levels also showed a higher proportion of impaired neurological status at discharge and morphological signs of brain injury. Conclusions: In CA patients following ROSC, initial serum phosphate levels >2.7 mmol/L predict higher mortality and impaired neurological outcome. Our data suggests that phosphate determination might improve the preciseness of the overall and neurologic prognostication in patients after CPR following ROSC.