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The process recommendations of the Ethics Section of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) for ethically based decision-making in intensive care medicine are intended to create the framework for a structured procedure for seriously ill patients in intensive care. The processes require appropriate structures, e.g., for effective communication within the treatment team, with patients and relatives, legal representatives, as well as the availability of palliative medical expertise, ethical advisory committees and integrated psychosocial and spiritual care services. If the necessary competences and structures are not available in a facility, they can be consulted externally or by telemedicine if necessary. The present recommendations are based on an expert consensus and are not the result of a systematic review or a meta-analysis.
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Cuidados Críticos , Tomada de Decisões , Medicina de Emergência , Humanos , Cuidados Críticos/normas , Medicina de Emergência/normas , Telemedicina , AlemanhaRESUMO
Post-acute sequelae of COVID-19 (PASC) are long-term consequences of SARS-CoV-2 infection that can substantially impair the quality of life. Underlying mechanisms ranging from persistent viruses to innate and adaptive immune dysregulation have been discussed. Here, we profiled the plasma of 181 individuals from the cohort study for digital health research in Germany (DigiHero), including individuals after mild to moderate COVID-19 with or without PASC and uninfected controls. We focused on soluble factors related to monocyte/macrophage biology and on circulating SARS-CoV-2 spike (S1) protein as a potential biomarker for persistent viral reservoirs. At a median time of 8 months after infection, we found pronounced dysregulation in almost all tested soluble factors, including both pro-inflammatory and pro-fibrotic cytokines. These immunological perturbations were remarkably independent of ongoing PASC symptoms per se, but further correlation and regression analyses suggested PASC-specific patterns involving CCL2/MCP-1 and IL-8 that either correlated with sCD162, sCD206/MMR, IFN-α2, IL-17A and IL-33, or IL-18 and IL-23. None of the analyzed factors correlated with the detectability or levels of circulating S1, indicating that this represents an independent subset of patients with PASC. These data confirm prior evidence of immune dysregulation and persistence of viral protein in PASC and illustrate its biological heterogeneity that still awaits correlation with clinically defined PASC subtypes.
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Síndrome de COVID-19 Pós-Aguda , Glicoproteína da Espícula de Coronavírus , Humanos , Biomarcadores , Estudos de Coortes , COVID-19/complicações , Progressão da Doença , Síndrome de COVID-19 Pós-Aguda/diagnóstico , Síndrome de COVID-19 Pós-Aguda/metabolismo , Qualidade de Vida , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/sangue , Glicoproteína da Espícula de Coronavírus/química , Macrófagos/metabolismoRESUMO
BACKGROUND: Clinical ethics case consultations (CECCs) provide a structured approach in situations of ethical uncertainty or conflicts. There have been increasing calls in recent years to assess the quality of CECCs by means of empirical research. This study provides detailed data of a descriptive quantitative and qualitative evaluation of a CECC service in a department of cardiology and intensive care at a German university hospital. METHODS: Semi-structured document analysis of CECCs was conducted in the period of November 1, 2018, to May 31, 2020. All documents were analysed by two researchers independently. RESULTS: Twenty-four CECCs were requested within the study period, of which most (n = 22; 92%) had been initiated by physicians of the department. The patients were an average of 79 years old (R: 43-96), and 14 (58%) patients were female. The median length of stay prior to request was 12.5 days (R: 1-65 days). The most frequent diagnoses (several diagnoses possible) were cardiology-related (n = 29), followed by sepsis (n = 11) and cancer (n = 6). Twenty patients lacked decisional capacity. The main reason for a CECC request was uncertainty about the balancing of potential benefit and harm related to the medically indicated treatment (n = 18). Further reasons included differing views regarding the best individual treatment option between health professionals and patients (n = 3) or between different team members (n = 3). Consensus between participants could be reached in 18 (75%) consultations. The implementation of a disease specific treatment intervention was recommended in five cases. Palliative care and limitation of further disease specific interventions was recommended in 12 cases. CONCLUSIONS: To the best of our knowledge, this is the first in-depth evaluation of a CECC service set up for an academic department of cardiology and intensive medical care. Patient characteristics and the issues deliberated during CECC provide a starting point for the development and testing of more tailored clinical ethics support services and research on CECC outcomes.
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Cardiologia , Consultoria Ética , Idoso , Cuidados Críticos , Ética Clínica , Feminino , Pessoal de Saúde , Humanos , Encaminhamento e ConsultaRESUMO
BACKGROUND: There is scarce evidence for mechanical circulatory support (MCS) in patients with influenza-related myocarditis complicated by refractory cardiogenic shock (rCS). We sought to investigate the impact of MCS using combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and micro-axial flow pumps (the ECMELLA concept) in influenza-related myocarditis complicated by rCS. METHODS: This is a prospective, observational analysis from the single centre HAnnover Cardiac Unloading REgistry (HACURE) from two recent epidemic influenza seasons. We analysed patients with verified influenza-associated myocarditis complicated by rCS who were admitted to our intensive care unit (ICU) on MCS. Subsequently, we performed a propensity score (PS) matched analysis to patients with acute myocardial infarction (AMI) complicated by rCS and non-ischaemic cardiomyopathy (DCM) related rCS. RESULTS: We describe a series of seven patients with rCS-complicated influenza-related myocarditis (mean age 56±10â years, 58% male, influenza A (n=2)/influenza B (n=5)). No patient had been vaccinated prior to the influenza season. MCS was provided using combined VA-ECMO and Impella micro-axial flow pump. In two patients with out-of-hospital cardiac arrest, VA-ECMO had been implanted for extracorporeal cardiopulmonary resuscitation. All patients died within 18â days of hospital admission. By PS-based comparison to patients with AMI- or DCM-related rCS and combined MCS, 30-day mortality was significantly higher in influenza-related rCS. CONCLUSION: Despite initial stabilisation with combined MCS in patients with rCS-complicated influenza-related myocarditis, the detrimental course of shock could not be stopped and all patients died. Influenza virus infection potentially critically affects other organs besides the heart, leading to irreversible end-organ damage that MCS cannot compensate for and, therefore, results in a devastating outcome.
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Miocardite , Orthomyxoviridae , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/complicações , Miocardite/terapia , Estudos Prospectivos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Resultado do TratamentoRESUMO
PURPOSE: The chemokine receptor CXCR4 is a promising target for molecular imaging of CXCR4+ cell types, e.g. inflammatory cells, in cardiovascular diseases. We speculated that a specific CXCR4 ligand, [68Ga]pentixafor, along with novel techniques for motion correction, would facilitate the in vivo characterization of CXCR4 expression in small culprit and nonculprit coronary atherosclerotic lesions after acute myocardial infarction by motion-corrected targeted PET/CT. METHODS: CXCR4 expression was analysed ex vivo in separately obtained arterial wall specimens. [68Ga]Pentixafor PET/CT was performed in 37 patients after stent-based reperfusion for a first acute ST-segment elevation myocardial infarction. List-mode PET data were reconstructed to five different datasets using cardiac and/or respiratory gating. Guided by CT for localization, the PET signals of culprit and various groups of nonculprit coronary lesions were analysed and compared. RESULTS: Ex vivo, CXCR4 was upregulated in atherosclerotic lesions, and mainly colocalized with CD68+ inflammatory cells. In vivo, elevated CXCR4 expression was detected in culprit and nonculprit lesions, and the strongest CXCR4 PET signal (median SUVmax 1.96; interquartile range, IQR, 1.55-2.31) was observed in culprit coronary artery lesions. Stented nonculprit lesions (median SUVmax 1.45, IQR 1.23-1.88; P = 0.048) and hot spots in naive remote coronary segments (median SUVmax 1.34, IQR 1.23-1.74; P = 0.0005) showed significantly lower levels of CXCR4 expression. Dual cardiac/respiratory gating provided the strongest CXCR4 PET signal and the highest lesion detectability. CONCLUSION: We demonstrated the basic feasibility of motion-corrected targeted PET/CT imaging of CXCR4 expression in coronary artery lesions, which was triggered by vessel wall inflammation but also by stent-induced injury. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of coronary atherosclerotic plaque.
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Complexos de Coordenação , Regulação Neoplásica da Expressão Gênica , Movimento , Peptídeos Cíclicos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores CXCR4/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Placa Aterosclerótica/complicações , Placa Aterosclerótica/fisiopatologia , Respiração , Estudos RetrospectivosRESUMO
OBJECTIVE: Regulator of G-protein signaling 5 (RGS5) is abundantly expressed in vascular smooth muscle cells (SMCs) and inhibits G-protein signaling by enhancing the guanosine triphosphate-hydrolyzing activity of Gα-subunits. In the present study, we investigated the effects of RGS5 on vascular SMC function in vitro and neointima formation after wire-induced injury in mice and determined the underlying mechanisms. APPROACH AND RESULTS: We found a robust expression of RGS5 in native arteries of C57BL/6 mice and a highly significant downregulation within neointimal lesions 10 and 21 days after vascular injury as assessed by quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry. In vitro, RGS5 was found significantly downregulated after mitogenic stimulation of human coronary artery SMCs. To restore RGS5 levels, SMCs were transduced with adenoviral vectors encoding wild-type RGS5 or a nondegradable mutant. RGS5-WT and, even more prominently, the C2A-RGS5 mutant prevented SMC proliferation and migration. In contrast, the siRNA-mediated knockdown of RGS5 significantly augmented SMC proliferation. Following overexpression of RGS5, fluorescence-activated cell sorting analysis of propidium iodide-stained cells indicated cell cycle arrest in G0/G1 phase. Mechanistically, inhibition of the phosphorylation of the extracellular signal-regulated kinase 1/2 and mitogen-activated protein kinase downstream signaling was shown to be responsible for the anti-proliferative effect of RGS5. Following wire-induced injury of the femoral artery in C57BL/6 mice, adenoviral-mediated overexpression of RGS5-WT or C2A-RGS5 significantly reduced SMC proliferation and neointima formation in vivo. CONCLUSIONS: Downregulation of RGS5 is an important prerequisite for SMC proliferation in vitro and in vivo. Therefore, reconstitution of RGS5 levels represents a promising therapeutic option to prevent vascular remodeling processes.
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Proliferação de Células , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Neointima , Proteínas RGS/metabolismo , Transdução de Sinais , Lesões do Sistema Vascular/metabolismo , Animais , Pontos de Checagem do Ciclo Celular , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Artéria Femoral/lesões , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Regulação da Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/lesões , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fosforilação , Proteínas RGS/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Reepitelização , Fatores de Tempo , Transdução Genética , Transfecção , Remodelação Vascular , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologiaRESUMO
Background: High blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with preserved ejection fraction (HFpEF). Since renal sympathetic denervation (RDN) reduces blood pressure in the long term, we aimed to investigate the long-term effect of RDN in patients with HFpEF in the present analysis. Methods: Patients previously enrolled in a local RDN registry who underwent high-frequency RDN with the use of the Symplicity Flex® renal denervation system between 2011 and 2014 were followed up. The patients were assessed by 24-h ambulatory blood pressure measurement, transthoracic echocardiography, and laboratory tests. We used the echocardiographic and biomarker criteria of the Heart Failure Association (HFA)-PEFF (Pre-test assessment, Echocardiography and Natriuretic Peptide Score, Funkctional testing, and Final aetiology) score to identify patients with HFpEF. Results: Echocardiographic assessment was available for 70 patients at a 9-year long-term follow-up. Of these patients, 21 had HFpEF according to the HFA-PEFF score. We found a significant reduction of the HFA-PEFF score from 5.48 ± 0.51 points at baseline to 4.33 ± 1.53 points at the 9-year follow-up (P < 0.01). This decrease was due to a greater reduction in morphological and biomarker subcategories [from 1.95 ± 0.22 to 1.43 ± 0.51 points (P < 0.01) and from 1.52 ± 0.52 to 0.90 ± 0.63 points (P < 0.01), respectively] than in the functional one. Morphologically, there was a reduction in left ventricular hypertrophy and left atrial dilation. Conclusions: The present analysis suggests that RDN may lead to a regression of the extent of HFpEF beyond a reduction in blood pressure and thus possibly contribute to an improvement in prognosis. More detailed information will be provided by ongoing randomized sham-controlled trials.
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Circulating endothelial cells (CEC) are arising as biomarkers for vascular diseases. However, whether they can be utilized as markers of endothelial cell (EC) senescence in vivo remains unknown. Here, we present a protocol to isolate circulating endothelial cells for a characterization of their senescent signature. Further, we characterize different models of EC senescence induction in vitro and show similar patterns of senescence being upregulated in CECs of aged patients as compared to young volunteers. Replication-(ageing), etoposide-(DNA damage) and angiotensin II-(ROS) induced senescence models showed the expected cell morphology and proliferation-reduction effects. Expression of senescence-associated secretory phenotype markers was specifically upregulated in replication-induced EC senescence. All models showed reduced telomere lengths and induction of the INK4a/ARF locus. Additional p14ARF-p21 pathway activation was observed in replication- and etoposide-induced EC senescence. Next, we established a combined magnetic activated- and fluorescence activated cell sorting (MACS-FACS) based protocol for CEC isolation. Interestingly, CECs isolated from aged volunteers showed similar senescence marker patterns as replication- and etoposide-induced senescence models. Here, we provide first proof of senescence in human blood derived circulating endothelial cells. These results hint towards an exciting future of using CECs as mirror cells for in vivo endothelial cell senescence, of particular interest in the context of endothelial dysfunction and cardiovascular diseases.
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Células Endoteliais , Doenças Vasculares , Humanos , Idoso , Células Endoteliais/metabolismo , Etoposídeo/farmacologia , Senescência Celular , Envelhecimento , Doenças Vasculares/metabolismoRESUMO
BACKGROUND: Intermittent fasting has shown positive effects on numerous cardiovascular risk factors. The INTERFAST-MI trial (Intermittent Fasting in Myocardial Infarction) has been designed to study the effects of intermittent fasting on cardiac function after STEM (ST-segment-elevation myocardial infarction) and the feasibility of future multicenter trials. METHODS: The INTERFAST-MI study was a prospective, randomized, controlled, nonblinded, single-center investigator-initiated trial. From October 1, 2020, to July 15, 2022, 48 patients were randomized to the study groups intermittent fasting or regular diet and followed for 6 months with follow-up visits at 4 weeks and 3 months. RESULTS: In all, 22 of 24 patients in the intermittent fasting group with a mean age of 58.54±12.29 years and 20 of 24 patients in the regular diet group with a mean age of 59.60±13.11 years were included in the intention-to-treat population. The primary efficacy end point (improvement in left ventricular ejection fraction after 4 weeks) was significantly greater in the intermittent fasting group compared with the control group (mean±SD, 6.636±7.122%. versus 1.450±4.828%; P=0.038). This effect was still significant and even more pronounced after 3 and 6 months. The patients in the intermittent fasting group showed a greater reduction in diastolic blood pressure and body weight compared with the control group. The mean adherence of patients in the intermittent fasting group was a median of 83.7% (interquartile range, 69.0%-98.4%) of all days. None of the patients from either group reported dizziness, syncope, or collapse. CONCLUSIONS: Our results suggest that intermittent fasting after myocardial infarction may be safe and could improve left ventricular function after STEMI. REGISTRATION: URL: https://www.drks.de; Unique identifier: DRKS00021784.
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Jejum , Infarto do Miocárdio com Supradesnível do Segmento ST , Função Ventricular Esquerda , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Função Ventricular Esquerda/fisiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Estudos Prospectivos , Resultado do Tratamento , Volume Sistólico/fisiologia , Fatores de Tempo , Jejum IntermitenteRESUMO
Extracorporeal life support systems (ECLS) are life-sustaining measures for severe cardiovascular diseases, serving as bridging treatment either until cardiovascular function is restored or alternative treatment, such as heart transplantation or the implantation of permanent ventricular assist devices is performed. Given the insufficient evidence and frequent urgency of implantation without initial patient consent, the ethical challenges and psychological burden for patients, relatives and the interprofessional intensive care team are significant. As with any treatment, an appropriate therapeutic goal for ECLS treatment based on the indications and patient informed consent is mandatory. In order to integrate the necessary ethical considerations into everyday clinical practice, a structured algorithm for handling ECLS is proposed here, which takes ethical aspects into due account.
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The rise in intensive care treatment procedures is accompanied by an increase in the complexity of decisions regarding the selection, administration and duration of treatment measures. Whether a treatment goal is desirable in an individual case and the treatment plan required to achieve it is acceptable for the patient depends on the patient's preferences, values and life plans. There is often uncertainty as to whether a patient-centered treatment goal can be achieved. The use of a time-limited treatment trial (TLT) as a binding agreement between the intensive care unit (ICU) team and the patient or their legal representative on a treatment concept over a defined period of time in the ICU can be helpful to reduce uncertainties and to ensure the continuation of intensive care measures in the patients' best interest.
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Unidades de Terapia Intensiva , Humanos , Alemanha , Unidades de Terapia Intensiva/ética , Cuidados Críticos/ética , Comunicação Interdisciplinar , Preferência do Paciente , Futilidade Médica/ética , Futilidade Médica/legislação & jurisprudência , Colaboração IntersetorialRESUMO
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.
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The rapid development of safe and effective vaccines helped to prevent severe disease courses after SARS-CoV-2 infection and to mitigate the progression of the COVID-19 pandemic. While there is evidence that vaccination may reduce the risk of developing post-COVID-19 conditions (PCC), this effect may depend on the viral variant. Therapeutic effects of post-infection vaccination have been discussed but the data for individuals with PCC remains inconclusive. In addition, extremely rare side effects after SARS-CoV-2 vaccination may resemble the heterogeneous PCC phenotype. Here, we analyze the plasma levels of 25 cytokines and SARS-CoV-2 directed antibodies in 540 individuals with or without PCC relative to one or two mRNA-based COVID-19 vaccinations as well as in 20 uninfected individuals one month after their initial mRNA-based COVID-19 vaccination. While none of the SARS-CoV-2 naïve individuals reported any persisting sequelae or exhibited PCC-like dysregulation of plasma cytokines, we detected lower levels of IL-1ß and IL-18 in patients with ongoing PCC who received one or two vaccinations at a median of six months after infection as compared to unvaccinated PCC patients. This reduction correlated with less frequent reporting of persisting gastrointestinal symptoms. These data suggest that post-infection vaccination in patients with PCC might be beneficial in a subgroup of individuals displaying gastrointestinal symptoms.
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In recent years, the number of intensive care treatments has increased significantly. About every fourth patient who dies in hospital receives intensive care. Structured prevention planning is important in order to implement the patient's wishes in situations of serious illness in which patients cannot express their wishes themselves. However, the implementation in practice can be problematic since intensive care situations are complex and rarely correspond to the concrete pre-arranged situations. Communication of the prognosis and the prognostic uncertainty is therefore crucial in order to determine the presumed will of the patient, especially in the context of the process of weighing up the benefits and burdens of intensive care therapies. Hospital treatment can be the reason for targeted preventive planning and avoid unnecessary intensive care treatment during the same stay. Documentation templates can help to record the results of preventive care planning clearly and comprehensibly in the medical file.
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Planejamento Antecipado de Cuidados , Assistência Terminal , Humanos , Cuidados Críticos/métodos , Prognóstico , Morte , Assistência Terminal/métodosRESUMO
Background: Renal sympathetic denervation (RDN) has been shown to lower arterial blood pressure both in the presence and in the absence of antihypertensive medication in an observation period of up to 3 years. However, long-term results beyond 3 years are scarcely reported. Methods: We performed a long-term follow-up on patients who were previously enrolled in a local renal denervation registry and who underwent radiofrequency RDN with the Symplicity Flex® renal denervation system between 2011 and 2014. The patients were assessed to evaluate their renal function by performing 24-hour ambulatory blood pressure measurement (ABPM), recording their medical history, and conducting laboratory tests. Results: Ambulatory blood pressure readings for 24â h were available for 72 patients at long-term follow-up (FU) [9.3 years (IQR: 8.5-10.1)]. We found a significant reduction of ABP from 150.1/86.1 ± 16.9/12.0â mmHg at baseline to 138.3/77.1 ± 16.5/11.1â mmHg at long-term FU (P < 0.001 for both systolic and diastolic ABP). The number of antihypertensive medications used by the patients significantly decreased from 5.4 ± 1.5 at baseline to 4.8 ± 1.6 at long-term FU (P < 0.01). Renal function showed a significant but expected age-associated decrease in the eGFR from 87.8 (IQR: 81.0-100.0) to 72.5 (IQR: 55.8-86.8)â ml/min/1.73â m2 (P < 0.01) in patients with an initial eGFR > 60â ml/min/1.73â m2, while a non-significant decrease was observed in patients with an initial eGFR < 60â ml/min/1.73â m2 at long-term FU [56.0 (IQR: 40.9-58.4) vs. 39.0 (IQR: 13.5-56.3)â ml/min/1.73â m2]. Conclusions: RDN was accompanied by a long-lasting reduction in blood pressure with a concomitant reduction in antihypertensive medication. No negative effects could be detected, especially with regard to renal function.
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BACKGROUND: In Germany, 70,000-100,000 persons per year suffer from out-of-hospital cardiac arrest (OHCA). Despite medical progress, survival rates with good neurological outcome remain low. For many important clinical issues, no or only insufficient evidence from randomised trials is available. Therefore, a systemic and standardised acquisition of the treatment course and of the outcome of OHCA patients is warranted. STUDY DESIGN: The German Cardiac Arrest Registry (G-CAR) is an observational, prospective, multicentre registry. It will determine the characteristics, initial treatment strategies, invasive procedures, revascularisation therapies and the use of mechanical circulatory support devices with a focus on extracorporeal cardiopulmonary resuscitation. A special feature is the prospective 12-month follow-up evaluating mortality, neurological outcomes and several patient-reported outcomes in the psychosocial domain (health-related quality of life, cognitive impairment, depression/anxiety, post-traumatic stress disorder and social reintegration). In a pilot phase of 24 months, 15 centres will include approximately 400 consecutive OHCA patients ≥ 18 years. Parallel to and after the pilot phase, scaling up of G-CAR to a national level is envisaged. CONCLUSION: G-CAR is the first national registry including a long-term follow-up for adult OHCA patients. Primary aim is a better understanding of the determinants of acute and long-term outcomes with the perspective of an optimised treatment. TRIAL REGISTRY: NCT05142124. German Cardiac Arrest Registry (G-CAR).
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Estudos Prospectivos , Resultado do Tratamento , Qualidade de Vida , Oxigenação por Membrana Extracorpórea/métodos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Sistema de RegistrosRESUMO
Dedifferentiation, migration, and proliferation of resident vascular smooth muscle cells (SMCs) are key components of neointima formation after vascular injury. Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in this process, but the complex regulation of STAT3-dependent genes and the functional significance of inhibiting this pathway during the development of vascular proliferative diseases remain elusive. In this study, we demonstrate that STAT3 was activated in neointimal lesions following wire-induced injury in mice. Phosphorylation of STAT3 induced trans-activation of cyclin D1 and survivin in SMCs in vitro and in neointimal cells in vivo, thus promoting proliferation and migration of SMCs as well as reducing apoptotic cell death. WP1066, a highly potent inhibitor of STAT3 signaling, abrogated phosphorylation of STAT3 and dose-dependently inhibited the functional effects of activated STAT3 in stimulated SMCs. The local application of WP1066 via a thermosensitive pluronic F-127 gel around the dilated arteries significantly inhibited proliferation of neointimal cells and decreased the neointimal lesion size at 3 weeks after injury. Even though WP1066 application attenuated the injury-induced up-regulation of the chemokine RANTES at 6 h after injury, there was no significant effect on the accumulation of circulating cells at 1 week after injury. In conclusion, these data identify STAT3 as a key molecule for the proliferative response of SMC and neointima formation. Moreover, inhibition of STAT3 by the potent and specific compound WP1066 might represent a novel and attractive approach for the local treatment of vascular proliferative diseases.
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Fármacos Cardiovasculares/farmacologia , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Neointima/prevenção & controle , Piridinas/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Tirfostinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL5/metabolismo , Ciclina D1/metabolismo , Modelos Animais de Doenças , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima/metabolismo , Neointima/patologia , Fosforilação , Regiões Promotoras Genéticas , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Survivina , Fatores de TempoRESUMO
Decisions with considerable medical and ethical implications are made in emergency departments every day. Despite time pressure and high workloads, they have to be arrived at in an expert manner in all dimensions. For immediate ethical decisions, structuring the decision-making process in the form of standard procedures can be helpful, provided that they are trained and practiced in an interdisciplinary and interprofessional manner. The support for ad hoc ethical decisions presented here recommends an "ethical team time out" for the evaluation of treatment choices, in a framework where the patient's will and medical indication are examined and completed in a structured manner. Further experts (ideally, an ad hoc clinical ethics consultation) should be consulted if the treatment measure is of questionable medical benefit and/or of questionable patient consent.
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Cuidados Críticos , Medicina de Emergência , Ética Médica , HumanosRESUMO
INTRODUCTION: Preclinical studies consistently show robust disease-modifying effects of intermittent fasting in animal models of cardiovascular disease. However, the impact of intermittent fasting on cardiovascular endpoints after myocardial infarction has not been investigated in a clinical trial so far. METHODS AND ANALYSIS: The INTERmittent FASTing after Myocardial Infarction (INTERFAST-MI) trial is a monocentric prospective randomised controlled non-confirmatory pilot study including 48 patients with ST-segment elevation myocardial infarction. They will be randomised in a 1:1 ratio to either intermittent fasting (daily time-restricted eating; consuming food for not more than 8 hours/day, fasting for at least 16 hours/day) or to a control group without a particular diet. The follow-up time is 6 months. The prespecified primary outcome is change in left ventricular systolic function at 4 weeks from baseline to estimate effect size required to establishing sample size and power calculation for a future full-scale trial. Secondary outcomes include protocol adherence, recruitment, major adverse cardiac events, revascularisation, changes in left ventricular systolic function at 3 and 6 months, patient weight, blood pressure, and serum markers of inflammation and cardiovascular disease. Enrolment began on 1 November 2020 and is expected to conclude in December 2021. ETHICS AND DISSEMINATION: The trial has received ethics approval from the Medical Ethics Committee of the Martin-Luther-University Halle-Wittenberg. Results of the study will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00021784.
Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Jejum , Humanos , Infarto do Miocárdio/terapia , Projetos Piloto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Background: Empagliflozin, an inhibitor of the sodium glucose co-transporter 2 (SGLT2) and developed as an anti-diabetic agent exerts additional beneficial effects on heart failure outcomes. However, the effect of empagliflozin on vascular cell function and vascular remodeling processes remains largely elusive. Methods/Results: Immunocytochemistry and immunoblotting revealed SGLT2 to be expressed in human smooth muscle (SMC) and endothelial cells (EC) as well as in murine femoral arteries. In vitro, empagliflozin reduced serum-induced proliferation and migration of human diabetic and non-diabetic SMCs in a dose-dependent manner. In contrast, empagliflozin significantly increased the cell count and migration capacity of human diabetic ECs, but not of human non-diabetic ECs. In vivo, application of empagliflozin resulted in a reduced number of proliferating neointimal cells in response to femoral artery wire-injury in C57BL/6J mice and prevented neointima formation. Comparable effects were observed in a streptozocin-induced diabetic model of apolipoprotein E-/- mice. Conclusive to the in vitro-results, re-endothelialization was not significantly affected in C57BL/6 mice, but improved in diabetic mice after treatment with empagliflozin assessed by Evan's Blue staining 3 days after electric denudation of the carotid artery. Ribonucleic acid (RNA) sequencing (RNA-seq) of human SMCs identified the vasoactive peptide apelin to be decisively regulated in response to empagliflozin treatment. Recombinant apelin mimicked the in vitro-effects of empagliflozin in ECs and SMCs. Conclusion: Empagliflozin significantly reduces serum-induced proliferation and migration of SMCs in vitro and prevents neointima formation in vivo, while augmenting EC proliferation in vitro and re-endothelialization in vivo after vascular injury. These data document the functional impact of empagliflozin on vascular human SMCs and ECs and vascular remodeling in mice for the first time.