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1.
Artif Organs ; 47(10): 1654-1662, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37358935

RESUMO

BACKGROUND: Mobilization is important in longer courses in intensive care unit (ICU), typical for patients requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). For patients supported with ECMO, especially out-of-bed mobilizations improve outcome. We hypothesized that utilization of a dual lumen cannula (DLC) for V-V ECMO would facilitate out-of-bed mobilization compared to single lumen cannulas (SLC). METHODS: Retrospective single center registry study including all V-V ECMO patients cannulated between 10/2010 and 05/2021 for respiratory failure. RESULTS: The registry included 355 V-V ECMO patients (median age 55.6 years, 31.8% female, 27.3% with preexisting pulmonary disease), 289/355 (81.4%) primary cannulated with DLC, and 66/355 (18.6%) using SLC. Both groups had similar pre-ECMO characteristics. The runtime of the first ECMO cannula was significantly longer in DLC compared to SLC (169 vs. 115 h, p = 0.015). The frequency of prone positioning during V-V ECMO was similar in both groups (38.4 vs. 34.8%, p = 0.673). There was no difference in in-bed mobilization (41.2 vs. 36.4%, for DLC and SLC, respectively, p = 0.491). Patients with DLC were more often mobilized out-of-bed (25.6 vs. 12.1%, OR 2.495 [95% CI 1.150 to 5.268], for DLC and SLC, respectively, p = 0.023). Hospital survival was similar in both groups (46.4 vs. 39.4%, for DLC and SLC, respectively, p = 0.339). CONCLUSION: Patients cannulated with a dual lumen cannula for V-V ECMO support were significantly more often mobilized out-of-bed. Since mobilization is important in prolonged ICU courses typical for ECMO patients, this might be an important benefit. Other benefits of DLC were the longer runtime of the initial cannula set and fewer suction events.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Oxigenação por Membrana Extracorpórea/efeitos adversos , Estudos Retrospectivos , Cateterismo , Cânula , Insuficiência Respiratória/terapia
2.
FASEB J ; 35(11): e21956, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34605573

RESUMO

MicroRNAs are key regulators of the cardiac response to injury. MiR-100 has recently been suggested to be involved in different forms of heart failure, but functional studies are lacking. In the present study, we examined the impact of transgenic miR-100 overexpression on cardiac structure and function during physiological aging and pathological pressure-overload-induced heart failure in mice after transverse aortic constriction surgery. MiR-100 was moderately upregulated after induction of pressure overload in mice. While in our transgenic model the cardiomyocyte-specific overexpression of miR-100 did not result in an obvious cardiac phenotype in unchallenged mice, the transgenic mouse strain exhibited less left ventricular dilatation and a higher ejection fraction than wildtype animals, demonstrating an attenuation of maladaptive cardiac remodeling by miR-100. Cardiac transcriptome analysis identified a repression of several regulatory genes related to cardiac metabolism, lipid peroxidation, and production of reactive oxygen species (ROS) by miR-100 overexpression, possibly mediating the observed functional effects. While the modulation of ROS-production seemed to be indirectly affected by miR-100 via Alox5-and Nox4-downregulation, we demonstrated that miR-100 induced a direct repression of the scavenger protein CD36 in murine hearts resulting in a decreased uptake of long-chain fatty acids and an alteration of mitochondrial respiratory function with an enhanced glycolytic state. In summary, we identified miR-100 as a modulator of cardiac metabolism and ROS production without an apparent cardiac phenotype at baseline but a protective effect under conditions of pressure-overload-induced cardiac stress, providing new insight into the mechanisms of heart failure.


Assuntos
Antígenos CD36/metabolismo , Insuficiência Cardíaca/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , NADPH Oxidase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Animais , Antígenos CD36/genética , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Células HEK293 , Insuficiência Cardíaca/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , NADPH Oxidase 4/genética , Ratos , Volume Sistólico/genética , Transfecção , Remodelação Ventricular/genética
3.
Artif Organs ; 46(12): 2469-2477, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35841283

RESUMO

BACKGROUND: The hospital mortality of patients suffering from pulmonary failure requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) or extracorporeal carbon dioxide removal (ECCO2 R) is high. It is unclear whether outcome correlates with a hospital's annual procedural volume. METHODS: Data on all V-V ECMO and ECCO2 R cases treated from 2007 to 2019 were retrieved from the German Institute for Medical Documentation and Information. Comorbidities and outcomes were assessed by DRG, OPS, and ICD codes. The study population was divided into 5 groups depending on annual hospital V-V ECMO and ECCO2 R volumes (<10 cases; 10-19 cases; 20-29 cases; 30-49 cases; ≥50 cases). Primary outcome was hospital mortality. RESULTS: A total of 25 096 V-V ECMO and 3607 ECCO2 R cases were analyzed. V-V ECMO hospitals increased from 89 in 2007 to 214 in 2019. Hospitals handling <10 cases annually increased especially (64 in 2007 to 149 in 2019). V-V ECMO cases rose from 807 in 2007 to 2597 in 2019. Over 50% of cases were treated in hospitals handling ≥30 cases annually. Hospital mortality was independent of the annual hospital procedural volume (55.3%; 61.3%; 59.8%; 60.2%; 56.3%, respectively, p = 0.287). We detected no differences when comparing hospitals handling <30 cases to those with ≥30 annually (p = 0.659). The numbers of ECCO2 R hospitals and cases has dropped since 2011 (287 in 2007 to 48 in 2019). No correlation between annual hospital procedural volume and hospital mortality was identified (p = 0.914). CONCLUSION: The number of hospitals treating patients requiring V-V ECMO and V-V ECMO cases rose from 2007 to 2019, while ECCO2 R hospitals and their case numbers decreased. We detected no correlation between annual hospital V-V ECMO or ECCO2 R volume and hospital mortality.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Humanos , Insuficiência Respiratória/terapia , Mortalidade Hospitalar , Hospitais , Estudos Retrospectivos
4.
Mol Med ; 27(1): 101, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488621

RESUMO

BACKGROUND: Diet-induced obesity can result in the development of a diverse spectrum of cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis and atherosclerotic disease. MicroRNAs have been described to be important regulators of metabolism and disease development. METHODS: In the current study, we investigated the effects of ubiquitous miR-100 overexpression on weight gain and the metabolic phenotype in a newly generated transgenic mouse strain under normal chow and high fat diet and used microarray expression analysis to identify new potential target genes of miR-100. RESULTS: While transgenic overexpression of miR-100 did not significantly affect weight and metabolism under a normal diet, miR-100 overexpressing mice showed a reduced weight gain under a high fat diet compared to wildtype mice, despite an equal calorie intake. This was accompanied by less visceral and subcutaneous fat development and lover serum LDL cholesterol. In addition, transgenic miR-100 mice were more glucose tolerant and insulin sensitive and demonstrated increased energy expenditure under high fat diet feeding. A comprehensive gene expression profiling revealed the differential expression of several genes involved in lipid storage- and metabolism, among them CD36 and Cyp4A14. Our data showed a direct regulation of CD36 by miR-100, leading to a reduced fatty acid uptake in primary hepatocytes overexpressing miR-100 and the downregulation of several downstream mediators of lipid metabolism such as ACC1, FABP4, FAS and PPARγ in the liver. CONCLUSIONS: Our findings demonstrate a protective role of miR-100 in high fat diet induced metabolic syndrome and liver steatosis, partially mediated by the direct repression of CD36 and attenuation of hepatic lipid storage, implicating miR-100 as a possible therapeutic target in liver steatosis.


Assuntos
Hipertrigliceridemia/etiologia , Hipertrigliceridemia/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Regiões 3' não Traduzidas , Animais , Biomarcadores , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Glucose/metabolismo , Hepatócitos/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Transgênicos , Fenótipo , Interferência de RNA , Transcriptoma , Aumento de Peso
5.
Crit Care ; 25(1): 410, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844654

RESUMO

BACKGROUND: There is limited information about the long-term outcome of patients suffering from acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Most studies focused on short- to mid-term follow-up. We aimed to investigate long-term survival and health-related quality of life (HRQL) in these patients. METHODS: We report retrospective data from a single-centre registry of patients with severe ARDS treated with VV ECMO at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 10/2010 and 06/2019. Follow-up data of all patients that survived the index hospitalisation were collected by telephone interviews from 02/2020 till 09/2020. Long-term survival, HRQL (Short-Form Health Survey-36 (SF-36), St. Georges Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS)) and the return to work rate were documented. RESULTS: In total, 289 patients were treated with VV ECMO during the study period (median age 55 years, 67% males, hospital survival 45%). After a median duration of 3.9 years, follow-up assessment was complete in 94 of 129 hospital survivors (73%). Fifty-three patients completed the HRQL assessment. Hospital survivors showed a high 6- and 12-month survival rate (89% and 85%, respectively). Estimated survival rate of those discharged alive from ICU was 68.5% (95%-CI 56.9-80.1%) after 9.7 years. These patients reported high levels of HRQL (median SF-36 total score 73) and only few pulmonary (median SGRQ total score 19) and mental limitations (median HAD-D score 2 and HAD-A score 3). In total, 80% of the patients were able to resume employment. CONCLUSION: This analysis of VV ECMO patients showed favourable long-term survival and high levels of HRQL suggesting promising prospects for VV ECMO survivors.


Assuntos
Oxigenação por Membrana Extracorpórea , Qualidade de Vida , Síndrome do Desconforto Respiratório , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Análise de Sobrevida
6.
J Thromb Thrombolysis ; 51(2): 301-307, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32653986

RESUMO

The novel coronavirus SARS-CoV-2 and the resulting disease COVID-19 causes pulmonary failure including severe courses requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). Coagulopathy is a known complication of COVID-19 leading to thrombotic events including pulmonary embolism. It is unclear if the coagulopathy also increases thrombotic circuit complications of the ECMO. Aim of the present study therefor was to investigate the rate of V-V ECMO complications in COVID-19. We conducted a retrospective registry study including all patients on V-V ECMO treated at our centre between 01/2018 and 04/2020. COVID-19 cases were compared non- COVID-19 cases. All circuit related complications resulting in partial or complete exchange of the extracorporeal system were registered. In total, 66 patients were analysed of which 11 (16.7%) were SARS-CoV-2 positive. The two groups did not differ in clinical parameters including age (COVID-19 59.4 vs. non-COVID-19 58.1 years), gender (36.4% vs. 40%), BMI (27.8 vs. 24.2) and severity of illness as quantified by the RESP Score (1pt. vs 1pt.). 28 days survival was similar in both groups (72.7% vs. 58.2%). While anticoagulation was similar in both groups (p = 0.09), centrifugal pump head thrombosis was more frequent in COVID-19 (9/11 versus 16/55 p < 0.01). Neither the time to first exchange (p = 0.61) nor blood flow at exchange (p = 0.68) did differ in both groups. D-dimer levels prior to the thrombotic events were significantly higher in COVID-19 (mean 15.48 vs 26.59, p = 0.01). The SARS-CoV-2 induced infection is associated with higher rates of thrombotic events of the extracorporeal system during V-V ECMO therapy.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19 , Oxigenação por Membrana Extracorpórea/efeitos adversos , Sistema de Registros , SARS-CoV-2 , Trombose , Idoso , COVID-19/sangue , COVID-19/mortalidade , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/etiologia , Trombose/mortalidade
7.
J Thromb Thrombolysis ; 52(1): 76-84, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33145663

RESUMO

Subpleural consolidations have been found in lung ultrasound in patients with COVID-19, possibly deriving from pulmonary embolism (PE). The diagnostic utility of impact of lung ultrasound in critical-ill patients with COVID-19 for PE diagnostics however is unclear. We retrospectively evaluated all SARS-CoV2-associated ARDS patients admitted to our ICU between March 8th and May 31th 2020. They were enrolled in this study, when a lung ultrasound and a computed tomography pulmonary angiography (CTPA) were documented. In addition, wells score was calculated to estimate the probability of PE. The CTPA was used as the gold standard for the detection of PE. Twenty out of 25 patients met the inclusion criteria. In 12/20 patients (60%) (sub-) segmental PE were detected by CT-angiography. Lung ultrasound found subpleural consolidations in 90% of patients. PE-typical large supleural consolidations with a size ≥ 1 cm were detectable in 65% of patients and were significant more frequent in patients with PE compared to those without (p = 0.035). Large consolidations predicted PE with a sensitivity of 77% and a specificity of 71%. The Wells score was significantly higher in patients with PE compared to those without (2.7 ± 0.8 and 1.7 ± 0.5, respectively, p = 0.042) and predicted PE with an AUC of 0.81. When combining the two modalities, comparing patients with considered/probable PE using LUS plus a Wells score ≥ 2 to patients with possible/unlikely PE in LUS plus a Wells score < 2, PE could be predicted with a sensitivity of 100% and a specificity of 80%. Large consolidations detected in lung ultrasound were found frequently in COVID-19 ARDS patients with pulmonary embolism. In combination with a Wells score > 2, this might indicate a high-risk for PE in COVID-19.


Assuntos
COVID-19/complicações , Regras de Decisão Clínica , Angiografia por Tomografia Computadorizada , Pulmão/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Ultrassonografia , Idoso , COVID-19/diagnóstico , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Valor Preditivo dos Testes , Embolia Pulmonar/etiologia , Sistema de Registros , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
8.
Artif Organs ; 45(9): 1050-1060, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33725377

RESUMO

Prognosis of patients suffering from acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. It is controverisal whether these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) while evidence on this topic is sparse. We report retrospective data of a single-center registry of patients with severe ARDS requiring ECMO support between October 2010 and June 2019. Patients were analyzed by their status of immunosuppression. ECMO weaning success and hospital survival were analyzed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared. A total of 288 patients were analyzed (age 55 years, 67% male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27% vs. 53%, P < .001 and 27% vs. 48% after PSM, P = .006). VFD (60 days) were lower for patients with immunosuppression (11.9 vs. 22.4, P < .001), and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35%, and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases, and HIV, respectively. In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the etiologies of immunosuppression which should be considered in decision making.


Assuntos
Oxigenação por Membrana Extracorpórea , Terapia de Imunossupressão , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Adulto , Feminino , Mortalidade Hospitalar , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida
9.
Neurocrit Care ; 34(3): 739-747, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33619668

RESUMO

BACKGROUND: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients. METHODS: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk. RESULTS: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders. CONCLUSIONS: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.


Assuntos
COVID-19/complicações , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/virologia , Síndrome do Desconforto Respiratório/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Hemorragia Cerebral/terapia , Cuidados Críticos , Oxigenação por Membrana Extracorpórea , Feminino , Alemanha , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros , Respiração Artificial , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
10.
Circ Res ; 122(3): 417-432, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29208678

RESUMO

RATIONALE: The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear. OBJECTIVE: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis. METHODS AND RESULTS: Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging. Mechanistically, miR-100 directly repressed several components of mammalian target of rapamycin complex 1-signaling, including mammalian target of rapamycin and raptor, which resulted in a stimulation of endothelial autophagy and attenuated nuclear factor κB signaling in vitro and in vivo. In a low-density lipoprotein receptor-deficient atherosclerotic mouse model, pharmacological inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in >70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. CONCLUSIONS: In summary, we describe an anti-inflammatory function of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mammalian target of rapamycin signaling and autophagy in the vascular system. Our findings of miR-100 as a potential protective anti-athero-miR suggest that the therapeutic replacement of this microRNA could be a potential strategy for the treatment of chronic inflammatory diseases, such as atherosclerosis, in the future.


Assuntos
Aterosclerose/patologia , Autofagia , Células Endoteliais/patologia , MicroRNAs/fisiologia , Vasculite/patologia , Animais , Doenças das Artérias Carótidas/metabolismo , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/genética , LDL-Colesterol/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Leucócitos/fisiologia , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de LDL/metabolismo , Sinvastatina/farmacologia , Organismos Livres de Patógenos Específicos , Serina-Treonina Quinases TOR/fisiologia , Transcriptoma
11.
Crit Care ; 24(1): 397, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641155

RESUMO

BACKGROUND: Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support. METHODS: We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching. RESULTS: A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p = 0.94) and hospital survival (36.8% vs. 36.7%, p = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden's Index) as compared to late or no PP (81.8% vs. 33.3%, p = 0.02). CONCLUSION: In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Decúbito Ventral/fisiologia , Síndrome do Desconforto Respiratório/terapia , Adulto , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente/efeitos adversos , Posicionamento do Paciente/métodos , Posicionamento do Paciente/normas , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Síndrome do Desconforto Respiratório/fisiopatologia , Estudos Retrospectivos
12.
Circulation ; 131(18): 1575-89, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25850724

RESUMO

BACKGROUND: Adaptive neovascularization after arterial occlusion is an important compensatory mechanism in cardiovascular disease and includes both the remodeling of pre-existing vessels to collateral arteries (arteriogenesis) and angiogenic capillary growth. We now aimed to identify regulatory microRNAs involved in the modulation of neovascularization after femoral artery occlusion in mice. METHODS AND RESULTS: Using microRNA-transcriptome analysis, we identified miR-155 as a downregulated microRNA during hindlimb ischemia. Correspondingly, inhibition of miR-155 in endothelial cells had a stimulatory effect on proliferation and angiogenic tube formation via derepression of its direct target gene angiotensin II type 1 receptor. Surprisingly, miR-155-deficient mice showed an unexpected phenotype in vivo, with a strong reduction of blood flow recovery after femoral artery ligation (arteriogenesis) dependent on the attenuation of leukocyte-endothelial interaction and a reduction of proarteriogenic cytokine expression. Consistently, miR-155-deficient macrophages exhibit a specific alteration of the proarteriogenic cytokine expression profile, which is partly mediated by the direct miR-155 target gene SOCS-1. CONCLUSIONS: Our data demonstrate that miR-155 exerts an antiangiogenic but proarteriogenic function in the regulation of neovascularization via the suppression of divergent cell-specific target genes and that its expression in both endothelial and bone marrow-derived cells is essential for arteriogenesis in response to hindlimb ischemia in mice.


Assuntos
Circulação Colateral/genética , Membro Posterior/irrigação sanguínea , Isquemia/genética , MicroRNAs/fisiologia , Neovascularização Fisiológica/genética , Animais , Artérias/fisiopatologia , Sequência de Bases , Movimento Celular , Citocinas/fisiologia , Regulação para Baixo , Endotélio Vascular/fisiopatologia , Artéria Femoral , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Fluxometria por Laser-Doppler , Leucócitos/fisiologia , Ligadura , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Dados de Sequência Molecular , Receptor Tipo 1 de Angiotensina/biossíntese , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/fisiologia , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/fisiologia
14.
Basic Res Cardiol ; 110(3): 32, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25916938

RESUMO

The inflammatory sequelae of ischemia-reperfusion injury (IRI) are a major causal factor of tissue injury in various clinical settings. MicroRNAs (miRs) are short, non-coding RNAs, which regulate protein expression. Here, we investigated the role of miR-155 in IR-related tissue injury. Quantifying microRNA-expression levels in a human muscle tissue after IRI, we found miR-155 expression to be significantly increased and to correlate with the increased expression of TNF-α, IL-1ß, CD105, and Caspase3 as well as with leukocyte infiltration. The direct miR-155 target gene SOCS-1 was downregulated. In a mouse model of myocardial infarction, temporary LAD ligation and reperfusion injury resulted in a smaller area of necrosis in miR-155-/- animals compared to wildtype animals. To investigate the underlying mechanisms, we evaluated the effect of miR-155 on inflammatory cell recruitment by intravital microscopy and on the generation of reactive oxygen species (ROS) of macrophages. Our intravital imaging results demonstrated a decreased recruitment of inflammatory cells in miR-155-/- animals during IRI. The generation of ROS in leukocytic cells of miR-155-/- animals was also reduced. RNA silencing of the direct miR-155 target gene SOCS-1 abrogated this effect. In conclusion, miR-155 aggravates the inflammatory response, leukocyte infiltration and tissue damage in IRI via modulation of SOCS-1-dependent generation of ROS. MiR-155 is thus a potential target for the treatment or prevention of IRI.


Assuntos
Quimiotaxia de Leucócito/fisiologia , Inflamação/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão/metabolismo , Migração Transendotelial e Transepitelial/fisiologia , Animais , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Humanos , Inflamação/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/genética , Explosão Respiratória/fisiologia , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Transfecção
18.
ASAIO J ; 70(3): e43-e45, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411927

RESUMO

For patients on venoarterial extracorporeal membrane oxygenation support where ready-to-wean criteria are met, complications during the decannulation are quite common. Management of these complications can be challenging as many of the remaining standard arterial access sites are in use or had prior closure by a closure device. In this case report of a 70-year-old patient, explantation of the arterial cannula with the help of a vascular closure device led to thrombotic occlusion of the distal femoral artery. Here, we describe a step-by-step guide outlining our approach on management of this complication. Most relevantly, a distal femoral access via the superficial femoral artery was used, and thrombus aspiration was done with the help of the AngioJet peripheral thrombectomy system.


Assuntos
Oxigenação por Membrana Extracorpórea , Humanos , Idoso , Extremidade Inferior , Remoção de Dispositivo , Artéria Femoral/cirurgia , Trombectomia
19.
Clin Res Cardiol ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186178

RESUMO

OBJECTIVES: To investigate the burden of disease of myocarditis in Germany and identify similarities and differences in myocarditis with or without COVID-19. METHODS: All patients hospitalized with myocarditis in Germany were included in this nationwide retrospective analysis. Data were retrieved from the Federal Statistical Office of Germany (DESTATIS) for the years from 2007 to 2022. The primary endpoint was hospital mortality. RESULTS: A total of 88,159 patients hospitalized with myocarditis were analyzed. Annual cases increased from 5100 in 2007 to 6593 in 2022 (p < 0.001 for trend) with higher incidence during winter months. Incidence per 100,000 inhabitants was 6.2 in 2007 rising to 7.8 in 2022 (p < 0.001 for trend). Hospital mortality remained constant at an average of 2.44% (p = 0.164 for trend). From 2020 to 2022, 1547/16,229 (9.53%) patients were hospitalized with both, myocarditis and COVID-19 (incidence 0.62/100,000 inhabitants and 180/100,000 hospitalizations with COVID-19). These patients differed significantly in most patient characteristics and had a higher rate of hospital mortality compared to myocarditis without COVID-19 (12.54% vs. 2.26%, respectively, p < 0.001). CONCLUSIONS: Myocarditis hospitalizations were slowly rising over the past 16 years with hospital mortality remaining unchanged. Incidence of hospitalizations with combined myocarditis and COVID-19 was low, but hospital mortality was high.

20.
ASAIO J ; 70(4): 293-298, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37934747

RESUMO

Mortality prediction for patients with the severe acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) is challenging. Clinical variables at baseline and on day 3 after initiation of ECMO support of all patients treated from October 2010 through April 2020 were analyzed. Multivariate logistic regression analysis was used to identify score variables. Internal and external (Monza, Italy) validation was used to evaluate the predictive value of the model. Overall, 272 patients could be included for data analysis and creation of the PREDICT VV-ECMO score. The score comprises five parameters (age, lung fibrosis, immunosuppression, cumulative fluid balance, and ECMO sweep gas flow on day 3). Higher score values are associated with a higher probability of hospital death. The score showed favorable results in derivation and external validation cohorts (area under the receiver operating curve, AUC derivation cohort 0.76 [95% confidence interval, CI, 0.71-0.82] and AUC validation cohort 0.74 [95% CI, 0.67-0.82]). Four risk classes were defined: I ≤ 30, II 31-60, III 61-90, and IV ≥ 91 with a predicted mortality of 28.2%, 56.2%, 84.8%, and 96.1%, respectively. The PREDICT VV-ECMO score suggests favorable performance in predicting hospital mortality under ongoing ECMO support providing a sound basis for further evaluation in larger cohorts.


Assuntos
Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Estudos Retrospectivos , Mortalidade Hospitalar , Síndrome do Desconforto Respiratório/terapia , Itália
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