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1.
J Clin Med ; 13(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38592110

RESUMO

Background: The timely initiation of extracorporeal membrane oxygenation (ECMO) is crucial for providing life support. However, delays can occur when perfusionists are not readily available. The Jena Method aims to address this issue by offering a wet-primed ECMO system that can be rapidly established without the perfusionist's presence. Methods: The goal was to ensure prompt ECMO initiation while maintaining patient safety. The method focuses on meeting hygienic standards, safe primed storage of the circuit, staff training, and providing clear step-by-step instructions for the ECMO unit. Results: Since implementing the Jena Method in 2015, 306 patients received VA-ECMO treatment. Bacterial tests confirmed the sterility of the primed ECMO circuits during a 14-day period. The functionality of all the components of the primed ECMO circuit after 14 days, especially the pump and oxygenator, were thoroughly checked and no malfunction was found to this day. To train staff for independent ECMO initiation, a step-by-step system involves safely bringing the ECMO unit to the intervention site and establishing all connections. This includes powering up, managing recirculation, de-airing the system, and preparing it for cannula connection. A self-developed picture-based guide assists in this process. New staff members learn from colleagues and receive quarterly training sessions by perfusionists. After ECMO deployment, the perfusionist provides a new primed system for a potential next patient. Conclusions: Establishing a permanently wet-primed on-demand extracorporeal life support circuit without direct perfusionist support is feasible and safe. The Jena Method enables rapid ECMO deployment and has the potential to be adopted in emergency departments as well.

3.
Infection ; 52(2): 685-690, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38133714

RESUMO

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.


Assuntos
Agranulocitose , Aspergilose , Pneumopatias , Linfo-Histiocitose Hemofagocítica , Pneumotórax , Sepse , Humanos , Feminino , Aspergillus flavus , Dipirona , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Hemorragia , Necrose , Linfo-Histiocitose Hemofagocítica/microbiologia
4.
J Clin Med ; 12(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37568295

RESUMO

BACKGROUND: Cardiogenic shock and arrest present as critical, life-threatening emergencies characterized by severely compromised tissue perfusion and inadequate oxygen supply. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) serves as a mechanical support system for patients suffering shock refractory to conventional resuscitation. Despite the utilization of VA-ECMO, clinical deterioration due to systemic inflammatory response syndrome (SIRS) resulting from the underlying shock and exposure of blood cells to the artificial surfaces of the ECMO circuit may occur. To address this issue, cytokine adsorbers offer a valuable solution by eliminating blood proteins, thereby controlling SIRS and potentially improving hemodynamics. Consequently, a prospective, randomized, blinded clinical trial will be carried out with ECMOsorb. METHODS AND STUDY DESIGN: ECMOsorb is a single-center, controlled, randomized, triple-blinded trial that will compare the hemodynamic effects of treatment with a VA-ECMO in combination with a cytokine adsorber (CytoSorb®, intervention) to treatment with VA-ECMO only (control) in patients with cardiogenic shock (with or without prior cardiopulmonary resuscitation (CPR)) requiring extracorporeal, hemodynamic support. Fifty-four patients will be randomized in a 1:1 fashion to the intervention or control group over a 36-month period. The primary endpoint of ECMOsorb is the improvement of the Inotropic Score (IS) 72 h after the intervention. Prognostic indicators, including mortality rates, hemodynamic parameters, laboratory findings, echocardiographic assessments, quality of life measurements, and clinical parameters, will serve as secondary outcome measures. The safety evaluation encompasses endpoints such as air embolisms, allergic reactions, peripheral ischemic complications, vascular complications, bleeding incidents, and stroke occurrences. CONCLUSIONS: The ECMOsorb trial seeks to assess the efficacy of a cytokine adsorber (CytoSorb®; CytoSorbents Europe GmbH, Berlin, Germany) in reducing SIRS and improving hemodynamics in patients with cardiogenic shock who are receiving VA-ECMO. We hypothesize that a reduction in cytokine levels can lead to faster weaning from inotropic and mechanical circulatory support, and ultimately to improved recovery.

5.
J Clin Med ; 12(8)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37109353

RESUMO

BACKGROUND: Hemolysis, a common adverse event associated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), may affect neuron-specific enolase (NSE) levels and potentially confound its prognostic value in predicting neurological outcomes in resuscitated patients without return of spontaneous circulation (ROSC) that require extracorporeal cardiopulmonary resuscitation (eCPR). Therefore, a better understanding of the relationship between hemolysis and NSE levels could help to improve the accuracy of NSE as a prognostic marker in this patient population. METHODS: We retrospectively analyzed the records of patients who received a VA-ECMO for eCPR between 2004 and 2021 and were treated in the medical intensive care unit (ICU) of the University Hospital Jena. The outcome was measured clinically by using the Cerebral Performance Category Scale (CPC) four weeks after eCPR. The serum concentration of NSE (baseline until 96 h) was analyzed by enzyme-linked immunosorbent assay (ELISA). To evaluate the ability of individual NSE measurements to discriminate, receiver operating characteristic (ROC) curves were calculated. Serum-free hemoglobin (fHb, baseline until 96 h) served as a marker for identifying a confounding effect of parallel hemolysis. RESULTS: 190 patients were included in our study. A total of 86.8% died within 4 weeks after ICU admission or remained unconscious (CPC 3-5), and 13.2% survived with a residual mild to moderate neurological deficit (CPC 1-2). Starting 24h after CPR, NSE was significantly lower and continued to decrease in patients with CPC 1-2 compared to the group with an unfavorable outcome of CPC 3-5. In addition, when evaluating on the basis of receiver operating characteristic curves (ROC), relevant and stable area under the curve (AUC) values for NSE could be calculated (48 h: 0.85 // 72 h: 0.84 // 96 h: 0.80; p < 0.01), and on the basis of a binary logistic regression model, relevant odds ratios for the NSE values were found even after adjusting for fHb regarding the prediction of an unfavorable outcome of CPC 3-5. The respective adjusted AUCs of the combined predictive probabilities were significant (48 h: 0.79 // 72 h: 0.76 // 96 h: 0.72; p ≤ 0.05). CONCLUSIONS: Our study confirms NSE as a reliable prognostic marker for poor neurological outcomes in resuscitated patients receiving VA-ECMO therapy. Furthermore, our results demonstrate that potential hemolysis during VA-ECMO does not significantly impact NSE's prognostic value. These findings are crucial for clinical decision making and prognostic assessment in this patient population.

6.
Diagnostics (Basel) ; 12(10)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36292031

RESUMO

Disseminated intravascular coagulation (DIC) is a systemic disease characterized by simultaneous thrombosis, bleeding, and partially excessive fibrinolysis. Systemic shock, trauma, bacterial toxins, and procoagulants-expressing solid and hematologic malignancies are common causes of this life-threatening hemorrhagic complication and often require treatment in intensive care units. We describe a case of an elderly man with recurrent severe bleeding events in the cause of DIC, including epistaxis, hemoptysis, hematuria, and gastrointestinal bleeding. Laboratory investigations revealed elevated prostate-specific antigen (PSA), suggesting an underlying prostate cancer. Despite intensified coagulatory therapy, the coagulation disorder could not be stabilized. A single injection of degarelix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, led to rapid stabilization of the coagulation and decreased PSA within days. One year after initiating androgen-deprivation therapy, there were recurrent transfusion-requiring bleeding events, and a concomitant PSA increase occurred, suggesting metastatic castration-resistant disease associated with DIC. This case emphasizes DIC as a possible primary phenomenon and indicator for the progression of the underlying malignancy, as well as the importance of etiological therapies in the management of DIC.

7.
J Clin Med ; 11(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35956238

RESUMO

INTRODUCTION: Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (Impella®) has been approved for that purpose. METHODS AND STUDY DESIGN: JenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CP® leads to improvement of hemodynamic parameters in patients with cardiogenic shock requiring extracorporeal, hemodynamic support. The primary outcomes of JenaMACS are changes in hemodynamic parameters measured by pulmonary artery catheterization and changes in echocardiographic parameters of left and right heart function before and after Impella® implantation at different support levels after 24 h of support. Secondary outcome measures are hemodynamic and echocardiographic changes over time as well as clinical endpoints such as mortality or time to hemodynamic stabilization. Further, laboratory and clinical safety endpoints including severe bleeding, stroke, neurological outcome, peripheral ischemic complications and occurrence of sepsis will be assessed. JenaMACS addresses essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and improve the outcome in those patients. CONCLUSION: The JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® assist device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and may improve outcome in those patients. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP®) 24 h after onset and will provide valuable data for acute interventional strategies or future prospective trials. However, JenaMACS, due to its proof-of-concept design, is limited by its single center protocol, with a small sample size and without a comparison group.

8.
Can Respir J ; 2022: 7135958, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265230

RESUMO

Background: Percutaneous catheter-based ultrasound-assisted thrombolysis (UACDT) is recommended for patients with intermediate-high-risk or high-risk pulmonary embolism (PE) in whom systemic thrombolysis has failed or is contraindicated. Aim: To evaluate the safety and efficiency of UACDT in patients with intermediate-high-risk or high-risk PE. Methods: Between October 2017 and January 2020, we performed UACDT using the EkoSonic™ Endovascular System (EKOS™) in 51 patients (21 males, age 63 ± 18 years) with a sPESI of 1.3 ± 0.7. The EKOS™-catheter was implanted within 24 h after admission. Over 15 hours, 11.5 mg of alteplase was administered per catheter. We evaluated right ventricular stress and cardiac biomarkers before and after UACDT. Results: 24 h post-UACDT, median RV/LV ratio decreased from 1.13 to 0.96 (p < 0.001) and the mean sPAP decreased from 47 ± 3 to 32 ± 2 mmHg + CVP (p < 0.0002). There were 6 major bleeding events resulting in transfusion. No stroke, myocardial infarction, right heart decompensation, or recurrent PE occurred. 31 patients (63%) were discharged without any signs of right ventricular stress. After at least 3 months, 73% of our patients did not show any signs of right ventricular dysfunction. The mean RV/LV ratio decreased to 0.75 ± 0.03 (p < 0.0001) in comparison with pre-UACDT, sPAP to 23 mmHg + CVP (p < 0.0001), and BNP to 40 pg/ml (p < 0.0001). Conclusions: The treatment with UACDT reduced right heart stress during the first 24 hours and midterm in patients with intermediate-high-risk or high-risk PE at an acceptable rate of severe complications.


Assuntos
Embolia Pulmonar , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Cateteres , Estudos de Viabilidade , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Resultado do Tratamento
9.
BMC Neurol ; 21(1): 456, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809608

RESUMO

BACKGROUND: This study aimed to assess the prognostic value regarding neurologic outcome of CT neuroimaging based Gray-White-Matter-Ratio measurement in patients after resuscitation from cardiac arrest. METHODS: We retrospectively evaluated CT neuroimaging studies of 91 comatose patients resuscitated from cardiac arrest and 46 non-comatose controls. We tested the diagnostic performance of Gray-White-Matter-Ratio compared with established morphologic signs of hypoxic-ischaemic brain injury, e. g. loss of distinction between gray and white matter, and laboratory parameters, i. e. neuron-specific enolase, for the prediction of poor neurologic outcomes after resuscitated cardiac arrest. Primary endpoint was neurologic function assessed with cerebral performance category score 30 days after the index event. RESULTS: Gray-White-Matter-Ratio showed encouraging interobserver variability (ICC 0.670 [95% CI: 0.592-0.741] compared to assessment of established morphologic signs of hypoxic-ischaemic brain injury (Fleiss kappa 0.389 [95% CI: 0.320-0.457]) in CT neuroimaging studies. It correlated with cerebral performance category score with lower Gray-White-Matter-Ratios associated with unfavourable neurologic outcomes. A cut-off of 1.17 derived from the control population predicted unfavourable neurologic outcomes in adult survivors of cardiac arrest with 100% specificity, 50.3% sensitivity, 100% positive predictive value, and 39.3% negative predictive value. Gray-White-Matter-Ratio prognostic power depended on the time interval between circulatory arrest and CT imaging, with increasing sensitivity the later the image acquisition was executed. CONCLUSIONS: A reduced Gray-White-Matter-Ratio is a highly specific prognostic marker of poor neurologic outcomes early after resuscitation from cardiac arrest. Sensitivity seems to be dependent on the time interval between circulatory arrest and image acquisition, with limited value within the first 12 h.


Assuntos
Parada Cardíaca , Substância Branca , Adulto , Coma/diagnóstico por imagem , Coma/etiologia , Parada Cardíaca/complicações , Parada Cardíaca/diagnóstico por imagem , Parada Cardíaca/terapia , Humanos , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Substância Branca/diagnóstico por imagem
10.
Chest ; 158(5): 1867-1875, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32629035

RESUMO

BACKGROUND: Herpes simplex virus type 1 (HSV-1) is frequently detected in the BAL fluid of patients on mechanical ventilation. RESEARCH QUESTION: The aim of the study was to investigate whether antiviral therapy is associated with improved overall survival within 30 days. STUDY DESIGN AND METHODS: This was a retrospective cohort study in four ICUs between January 2011 and December 2017. All adult patients on mechanical ventilation with a respiratory tract infection with positive polymerase chain reaction testing for HSV-1 in the BAL were included. Patients already receiving antiviral agents on the day BAL was performed were excluded. We performed uni- and multivariable Cox and logistic regression modeling. RESULTS: Overall, 306 patients were included in the analysis. Among them, 177 patients (57.8%) received antiviral therapy (90.9% acyclovir, 6.2% ganciclovir, 2.9% both). The overall 30-day mortality rate was 42.4% (n = 75) in the antiviral treatment group and 50.4% (n = 65) in the control group. The adjusted hazard ratio (HR) for the primary outcome was 0.62 (95% CI, 0.44-0.87; P = .005), indicating better overall survival within 30 days for the antiviral-treated group than for the untreated group. This benefit was also present in the subgroup of patients without immunosuppression (n = 246; adjusted HR, 0.53; 95% CI, 0.36-0.78; P = .001). Overall, the median lengths of hospital stay (31 vs 24 days, P = .002) and ICU stay (24 vs 17 days, P < .001), and the duration of mechanical ventilation (18 vs 11 days, P < .001), were longer for patients with therapy. No evidence for the treatment-related deterioration of renal function was observed. INTERPRETATION: These data suggest that detection of HSV-1 in the BAL of patients on mechanical ventilation may be of clinical significance and that specific antiviral treatment may improve clinical outcomes. However, this needs to be proven in multicenter randomized controlled trials before implementation into the clinical routine.


Assuntos
Aciclovir/administração & dosagem , Líquido da Lavagem Broncoalveolar/virologia , Ganciclovir/administração & dosagem , Herpes Simples , Herpesvirus Humano 1 , Unidades de Terapia Intensiva/estatística & dados numéricos , Respiração Artificial/métodos , Infecções Respiratórias , Antivirais/administração & dosagem , Feminino , Alemanha/epidemiologia , Herpes Simples/diagnóstico , Herpes Simples/mortalidade , Herpes Simples/terapia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Infecções Respiratórias/mortalidade , Infecções Respiratórias/terapia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Resultado do Tratamento , Virologia/métodos , Virologia/estatística & dados numéricos
11.
Biochim Biophys Acta Mol Cell Res ; 1866(9): 1398-1411, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31150695

RESUMO

Emerging evidence suggests that arginase contributes to endothelial dysfunction in diabetes. Intracellular signaling pathways, which interplay between arginase and eNOS enzyme activity leading to the development of endothelial dysfunction in hyperglycemia are not fully understood. Here, we analyzed the possible involvement of hyperglycemia (HG) induced arginase expression in eNOS protein regulation and activity and also the impact of arginase inhibition on eNOS activity. Furthermore, the roles of p38 MAPK and Erk1/2 phosphorylation in upregulation of arginase expression and eNOS dysregulation in endothelial cells (ECs) under hyperglycemia were evaluated. Protein analysis showed a concurrent increase in arginase I expression and decrease in eNOS expression and phosphorylation at Ser1177 under HG conditions. There was no simultaneous change in phosphorylation of eNOS at Thr495 in HG. Arginase inhibition prevented increased arginase activity, restored impaired NO bioavailability and reduced superoxide anion generation. Inhibition of MAP-kinases demonstrated that, unlike Erk1/2, p38 MAPK is an upstream activator in a signaling cascade leading to increased arginase I in HG conditions. P38 MAPK protein expression and phosphorylation were increased in response to HG. In the presence of a p38 MAPK inhibitor, HG-induced arginase expression was blunted. Although Erk1/2 was activated in HG, increased arginase expression was not blocked by co-treatment with an Erk1/2 inhibitor. Activation of both, p38 MAPK and Erk1/2 in HG, induced a downregulation in eNOS activity. Hence, applying MAPK inhibitors increased eNOS phosphorylation in HG. In conclusion, these findings demonstrate contributions of arginase I in the development of endothelial cell dysfunction under HG conditions via impaired eNOS regulation, which maybe mediated by p38 MAPK.


Assuntos
Arginase/metabolismo , Células Endoteliais/metabolismo , Hiperglicemia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Humanos , Hiperglicemia/complicações , Sistema de Sinalização das MAP Quinases , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Superóxidos , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Int J Cardiol ; 291: 96-104, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31155332

RESUMO

For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Coração Auxiliar/tendências , Choque Cardiogênico/epidemiologia , Choque Cardiogênico/terapia , Europa (Continente)/epidemiologia , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/tendências , Insuficiência Cardíaca/diagnóstico , Hemodinâmica/fisiologia , Humanos , Balão Intra-Aórtico/métodos , Balão Intra-Aórtico/tendências , Choque Cardiogênico/diagnóstico
13.
Heart Fail Rev ; 23(6): 831-839, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30058015

RESUMO

Patients in cardiogenic shock and acute heart failure show high mortality and morbidity despite aggressive and invasive methods such as percutaneous coronary intervention and the use of mechanical support devices. Percutaneous implantation of active hemodynamic support is often the only option for hemodynamic stabilization of patients in cardiogenic shock. Therefore, current guidelines support the use of these devices. Standardized protocols and clinical algorithms for the use of these support devices decrease mortality in these patients. The aim of this review is an overview of current therapies of cardiogenic shock with special focus on mechanical support devices and the suggestion of a clinical algorithm for the differential use of current devices as well as the hemodynamic monitoring of such patients in order to reduce mortality in cardiogenic shock.


Assuntos
Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Coração Auxiliar , Balão Intra-Aórtico , Choque Cardiogênico/terapia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Fatores de Risco , Choque Cardiogênico/etiologia
14.
Int J Mol Sci ; 18(11)2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29117120

RESUMO

Pulmonary vascular remodeling is a pathophysiological feature that common to all classes of pulmonary hypertension (PH) and right ventricular dysfunction, which is the major prognosis-limiting factor. Vascular, as well as cardiac tissue remodeling are associated with a re-expression of fetal variants of cellular adhesion proteins, including tenascin-C (Tn-C). We analyzed circulating levels of the fetal Tn-C splicing variants B⁺ and C⁺ Tn-C in serum of PH patients to evaluate their potential as novel biomarkers reflecting vascular remodeling and right ventricular dysfunction. Serum concentrations of B⁺ and C⁺ Tn-C were determined in 80 PH patients and were compared to 40 healthy controls by enzyme-linked immunosorbent assay. Clinical, laboratory, echocardiographic, and functional data were correlated with Tn-C levels. Serum concentrations of both Tn-C variants were significantly elevated in patients with PH (p < 0.05). Significant correlations could be observed between Tn-C and echocardiographic parameters, including systolic pulmonary artery pressure (B⁺ Tn-C: r = 0.31, p < 0.001, C⁺ Tn-C: r = 0.26, p = 0.006) and right atrial area (B⁺ Tn-C: r = 0.46, p < 0.001, C⁺ Tn-C: r = 0.49, p < 0.001), and laboratory values like BNP (B⁺ Tn-C: r = 0.45, p < 0.001, C⁺ Tn-C: r = 0.42, p < 0.001). An inverse correlation was observed between Tn-C variants and 6-minute walk distance as a functional parameter (B⁺ Tn-C: r = -0.54, p < 0.001, C⁺ Tn-C: r = -0.43, p < 0.001). In a multivariate analysis, B⁺ Tn-C, but not C⁺ Tn-C, was found to be an independent predictor of pulmonary hypertension. Both fetal Tn-C variants may represent novel biomarkers that are capable of estimating both pulmonary vascular remodeling and right ventricular load. The potential beneficial impact of Tn-C variants for risk stratification in patients with PH needs further investigation.


Assuntos
Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/complicações , Tenascina/sangue , Remodelação Vascular , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/etiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética , Tenascina/genética , Teste de Caminhada
15.
Dis Markers ; 2016: 3695454, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27635109

RESUMO

Background and Aims. Fibronectin containing the extra domain A (ED-A(+) Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A(+) Fn in serum of heart failure patients. Methods. ED-A(+) Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A(+) Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A(+) Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: -0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A(+) Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A(+) Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A(+) Fn.


Assuntos
Cardiomiopatia Dilatada/sangue , Fibronectinas/sangue , Insuficiência Cardíaca/sangue , Isquemia Miocárdica/sangue , Remodelação Ventricular , Idoso , Biomarcadores/sangue , Cardiomiopatia Dilatada/patologia , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Volume Sistólico
16.
Wien Klin Wochenschr ; 128(23-24): 864-869, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27525745

RESUMO

BACKGROUND: Heart failure is known to be a major public health problem. Fluid redistribution contributes to acute heart failure; therefore, knowledge of hemodynamic parameters could be important for optimizing outcomes. The pulse contour cardiac output monitor PiCCO uses the single thermal indicator technique and pulse contour analysis to calculate hemodynamic parameters of preload, afterload, cardiac output, systemic vascular resistance and extravascular lung water. OBJECTIVES: We primarily aimed to describe values and parameters seen in acute heart failure patients admitted to the intensive care unit (ICU) and secondly to investigate associations between hemodynamic measurements and survival data. MATERIAL AND METHODS: In this study 420 consecutive patients admitted to a tertiary medical university hospital ICU between January 2004 and December 2009 were retrospectively investigated. The study sample was divided into two subgroups: patients monitored by PiCCO (n = 47) and those not monitored by thermodilution measurements (n = 373). No predetermined treatment algorithm based on knowledge obtained by the PiCCO monitor was used and measurements were individually interpreted by the treating physician. The PiCCO monitor measurements were carried out according to manufacturer's directions. RESULTS: Patients with PiCCO monitoring were clinically in poorer health with a mean simplified acute physiology score II (SAPS2) of 45 ± 17 vs. 56 ± 20 (p < 0.01). The ICU mortality (22 % vs. 38 %, p = 0.02) and, at least as a tendency, long-term-mortality were increased in patients monitored by PiCCO (RR 1.49, 95 % CI 0.96-2.31, p = 0.08). We provide hemodynamic measurements in acute heart failure patients: cardiac index (2.7 ± 1.2 l/min/m²) was reduced, preload and extravascular lung water index (EVLWI, 11.5 ± 5.1 ml/kg body weight), representing lung edema, were increased. CONCLUSION: We provide real world values for PiCCO parameters in acutely decompensated heart failure. In our study patients who were clinically in poorer health were monitored with PiCCO, resulting in increased mortality in this group. Further prospective studies to investigate the effects of treatment decisions triggered by information obtained by PiCCO monitoring for patients in acute heart failure are needed.


Assuntos
Débito Cardíaco , Água Extravascular Pulmonar , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Testes de Função Respiratória/métodos , Termodiluição/métodos , Idoso , Determinação da Pressão Arterial/métodos , Diagnóstico por Computador/métodos , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resistência Vascular
17.
Clin Res Cardiol ; 105(3): 196-205, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26303097

RESUMO

INTRODUCTION: Cardiac arrest is the major cause of sudden death in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) employs extracorporeal membrane oxygenation (ECMO) in patients without return of spontaneous circulation (ROSC) by conventional cardiopulmonary resuscitation (CPR). Aim of the current study was to assess short- and long-term outcome in patients treated with ECPR in our tertiary center and to identify predictors of outcome. METHODS: We retrospectively collected data of all patients treated with ECPR at our institution from 2002 to 2013. Outcome was assessed according to patient records; good neurological outcome was defined as cerebral performance category 1 or 2. Quality of life data was collected using EQ-5 questionnaire. Uni- and multivariate analysis was applied to identify predictors of outcome. RESULTS: One-hundred and seventeen patients were included into the study. Weaning from ECMO was successful in 61 (52 %) patients. Thirty-day survival endpoint was achieved by 27 (23 %) patients. Good neurological outcome was present in 17 (15 %) patients. Multivariate analysis revealed baseline serum lactate as the strongest predictor of outcome, whereas age and out-of-hospital CPR did not predict outcome. The optimal lactate cut-off to discriminate outcome was determined at 4.6 mmol/l [HR 3.55 (2.29-5.49), p < 0.001, log-rank test]. CONCLUSION: ECPR represents a treatment option in patients without ROSC after conventional CPR rescuing 15 % of patients with good neurological outcome. Serum lactate may play a crucial role in patient selection for ECPR.


Assuntos
Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/mortalidade , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Parada Cardíaca/sangue , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Humanos , Ácido Láctico/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Seleção de Pacientes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
18.
J Diabetes Complications ; 29(8): 1130-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26361811

RESUMO

PURPOSE: Diabetes mellitus represents an increasing problem for patients and health care systems worldwide. We sought to investigate the effect of diabetes and its associated comorbidities on long-term survival and quality of life following an admission to a medical intensive care unit (ICU). METHODS: A total of 6662 consecutive patients admitted to ICU between 2004 and 2009 were included (patients with diabetes n=796, non-diabetic patients n=5866). The primary endpoint of the study was death of any cause. Data on mortality was collected upon review of medical records or phone interviews. Moreover, a questionnaire was sent to 500 randomly selected patients addressing Health related Quality of Life (HrQoL) after ICU treatment. RESULTS: Overall mortality did not differ significantly between diabetic and non-diabetic patients after ICU treatment (mean follow-up time: 490 days). For a subgroup of patients already exhibiting comorbidities associated with diabetes, the mortality rate was significantly higher (p=0.022). Regarding quality of life, no differences were found between groups. CONCLUSIONS: Diabetes was not associated with increased mortality or reduced quality of life in a general population of medical ICU patients. However, once comorbidities associated with diabetes occurred, the survival rate of patients with comorbidities associated with hyperglycemia was significantly reduced.


Assuntos
Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/fisiopatologia , Unidades de Terapia Intensiva , Qualidade de Vida , Idoso , Estudos de Coortes , Comorbidade , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Feminino , Seguimentos , Alemanha/epidemiologia , Hospitais Universitários , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária
19.
Clin Biochem ; 48(16-17): 1048-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26169241

RESUMO

OBJECTIVES: Red cell distribution width was shown to reliably predict mortality and morbidity in numerous clinical settings, including patients hospitalized on surgical intensive care units (ICU). Patients hospitalized on an ICU usually comprise a very heterogeneous patient population. The aim of this analysis was to investigate whether (1) RDW is related to survival outcomes in patients hospitalized on a medical ICU and (2) the prognostic value of RDW is dependent on the diagnosis that led to ICU admission. METHODS: 829 patients hospitalized on the medical ICU of a tertiary care hospital were retrospectively investigated. Patients were divided in two groups according to the main diagnosis that led to ICU admission. Group 1: non-infectious cardiac disease and group 2: other. The prognostic value of RDW for ICU- and long-term mortality was investigated for the entire patient cohort as well as for the two subgroups. RESULTS: The median RDW of the whole study population was 16.1%. Patients with an RDW above this threshold were exposed to an increased risk for ICU mortality (34.4% vs. 17.2%, p<0.001) and long-term mortality (log-rank p<0.001). Similarly, this cut-off was able to distinguish patients with an elevated risk for death in subgroup 2 (ICU mortality: 37.9% vs. 19.2%, p<0.001; long-term mortality: log-rank p<0.001). In subgroup 1, this value was not able to identify patients with an increased risk for ICU-mortality (17.6% vs. 11.8%, p=0.26) as well as long-term mortality (log-rank p=0.3). CONCLUSIONS: Data of this analysis revealed that (1) RDW is a powerful predictor for ICU- and long-term mortality in patients hospitalized on a medical ICU and (2) RDW cut-offs to assess risk for death differ according to the main diagnosis that led to ICU admission.


Assuntos
Índices de Eritrócitos/fisiologia , Eritrócitos/fisiologia , Idoso , Causas de Morte , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
20.
Biomed Res Int ; 2015: 940910, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25710036

RESUMO

INTRODUCTION: Obesity during adolescence is an increasing problem for both the individual and health care systems alike. In Western world countries, childhood adiposity has reached epidemic proportions. It is known that elevated levels of proinflammatory cytokines can be found in the plasma of obese patients. In this study, we sought to determine the relation between IL-12p40, IL-12p70, and Interleukin-16 (IL-16) in overweight adolescents. MATERIALS AND METHODS: Seventy-nine male Caucasian adolescents aged 13-17 years were included in this study. Thirty-seven of them had a body mass index (BMI) above the 90th age-specific percentile. Il-12p40, IL-12p70, and IL-16 were measured from plasma using Luminex multiplex technology. RESULTS: Both IL-12p40 and IL-16 concentrations were significantly increased in overweight subjects compared to normal weight controls (IL-12p40: 1086.6 pg/mL ± 31.7 pg/mL SEM versus 1228.6 pg/mL ± 43.5 pg/mL SEM; IL-16 494.0 pg/mL ± 29.4 pg/mL SEM versus 686.6 pg/mL ± 52.5 pg/mL SEM, P < 0.05 and P < 0.01, resp.). No differences were found for IL-12p70. CONCLUSIONS: Based on these results, we believe that the increased levels of IL-12p40 and IL-16 are associated with an ongoing inflammatory response in obese individuals and could lead to the development of disease conditions related to obesity.


Assuntos
Subunidade p40 da Interleucina-12/sangue , Interleucina-12/sangue , Interleucina-16/sangue , Sobrepeso/sangue , Sobrepeso/diagnóstico , Adolescente , Biomarcadores/sangue , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Regulação para Cima
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