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1.
Burns ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35012801

RESUMO

INTRODUCTION: Lactate albumin ratio (LAR) has been used as a prognostic marker associated with organ failure in critically ill septic patients. LAR and its association with outcomes has never been studied in burned patients. The aim of this study was to evaluate the ability of LAR to predict 28-day mortality. METHODS: A retrospective cohort study including all burn patients hospitalized in intensive care unit. The primary endpoint was the 28-day mortality. RESULTS: One thousand three hundred thirty four patients were screened, and 471 were included between June 2012 and December 2018. Briefly, the population study was mainly composed by men (249, 59.1%), the median age, TBSA burned, full thickness, ABSI and IGS2 were 52 [34-68], 20 [10-40], 8 [1-23], 7 [5-9] and 25 [15-40] respectively. Fifty-two patients (12.4%) died at day 28 after admission. At admission, the LAR level was lower in 28-day survivors compared non-survivors (0.05 [0.04, 0.08] vs 0.12 [0.07, 0.26], p < 0.001 respectively). In multivariate analysis accounting for ABSI, LAR levels at admission> 0.13 was independently associated with 28-day mortality (adjusted OR = 3.98 (IC95 1.88-8.35)). The ability of LAR at admission to discriminate 28-day mortality showed an AUC identical when compared to SOFA and ABSI scores (0.81 (IC95 0.74-0.88), 0.80 (IC95 0.72-0.85) and (0.85 (IC95 0.80-0.90), p < 0.05, respectively). Patients with LAR levels ≥ 0.13 at admission had higher 28-day mortality (40.6% vs 6.8%, p < 0.001, HR 7.39 (IC95 4.28-12.76)). CONCLUSION: At admission, LAR is an easy and reliable marker independently associated to 28-day mortality in patients with severe burn injury, but prediction by LAR does not perform better than lactate level alone.

2.
Eur J Heart Fail ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014132

RESUMO

In order to ensure that the next generation of heart failure specialists will receive high-quality training, this document outlines the new European training and certification requirements for physicians with an interest in heart failure and for those working in certified heart failure centres, required by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

3.
Artigo em Inglês | MEDLINE | ID: mdl-35001023

RESUMO

BACKGROUND: Establishing neurological prognoses in traumatic brain injury (TBI) patients remains challenging. To help physicians in the early management of severe TBI, we have designed a visual score (ICEBERG score) including multimodal monitoring and treatment-related criteria. We evaluated the ICEBERG scores among patients with severe TBI to predict the 28-day mortality and long-term disability (Extended Glasgow Outcome Score (GOSE) at 3 years). Additionally, we made a preliminary assessment of the nurses and doctors on the uptake and reception to the use of the ICEBERG visual tool. METHODS: This study was part of a larger prospective cohort study of 207 patients with severe TBI in the Parisian region (PariS-TBI study). The ICEBERG score included 6 variables from multimodal monitoring and treatment-related criteria: cerebral perfusion pressure (CPP), intracranial pressure (ICP), body temperature, sedation depth, arterial partial pressure of CO2 and blood osmolarity. The primary outcome measures included the ICEBERG score and its relationship with hospital mortality and GOSE. RESULTS: The hospital mortality was 21% (45/207). The ICEBERG score baseline value and changes during the 72nd first hours were more strongly associated with TBI prognosis than the ICEBERG parameters measured individually. Interestingly, when the clinical and CT parameters at admission were combined with the ICEBERG score at 48 h using a multimodal approach, the predictive value was significantly increased (AUC = 0.92). Furthermore, comparing the ICEBERG visual representation with the traditional numerical readout revealed that changes in patient vitals were more promptly detected using ICEBERG representation (p < 0.05). CONCLUSIONS: The ICEBERG score could represent a simple and effective method to describe severity in TBI patients, where a high score is associated with increased mortality and disability. Additionally, ICEBERG representation could enhances the recognition of unmet therapeutic goals and dynamic evolution of the patient's condition. These preliminary results must be confirmed in a prospective manner. STUDY TYPE: Prognostic. LEVEL OF EVIDENCE: Level III.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35040931

RESUMO

The current European Society of Cardiology (ESC) Heart Failure Guidelines are the most comprehensive ESC document covering heart failure to date; however, the section focused on acute heart failure remains relatively concise. Although several topics are more extensively covered than in previous versions, including some specific therapies, monitoring and disposition in the hospital, and the management of cardiogenic shock, the lack of high-quality evidence in acute, emergency, and critical care scenarios, poses a challenge for providing evidence-based recommendations, in particular when by comparison the data for chronic heart failure is so extensive. The paucity of evidence and specific recommendations for the general approach and management of acute heart failure in the emergency department is particularly relevant, because this is the setting where most acute heart failure patients are initially diagnosed and stabilized. The clinical phenotypes proposed are comprehensive, clinically relevant and with minimal overlap, whilst providing additional opportunity for discussion around respiratory failure and hypoperfusion.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35048106

RESUMO

AIMS: To provide an overview of the role of cardiovascular (CV) imaging in facilitating and advancing the field of precision medicine in CV disease. METHODS AND RESULTS: Non-invasive CV imaging is essential to accurately and efficiently phenotype patients with heart disease, including coronary artery disease (CAD) and heart failure (HF). Various modalities, such as echocardiography, nuclear cardiology, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR), and invasive coronary angiography, and in some cases a combination, can be required to provide sufficient information for diagnosis and management. Taking CAD as an example, imaging is essential for the detection and functional assessment of coronary stenoses, as well as for the quantification of cardiac function and ischaemic myocardial damage. Furthermore, imaging may detect and quantify coronary atherosclerosis, potentially identify plaques at increased risk of rupture, and guide coronary interventions. In patients with HF, imaging helps identify specific aetiologies, quantify damage, and assess its impact on cardiac function. Imaging plays a central role in individualizing diagnosis and management and to determine the optimal treatment for each patient to increase the likelihood of response and improve patient outcomes. CONCLUSIONS: Advances in all imaging techniques continue to improve accuracy, sensitivity, and standardization of functional and prognostic assessments, and identify established and novel therapeutic targets. Combining imaging with artificial intelligence, machine learning and computer algorithms, as well as with genomic, transcriptomic, proteomic, and metabolomic approaches, will become state of the art in the future to understand pathologies of CAD and HF, and in the development of new, targeted therapies.

6.
J Clin Microbiol ; : JCM0216921, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985983

RESUMO

Introduction: Diagnosis of COVID-19 associated pulmonary aspergillosis remains unclear especially in non-immunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. Methods: All successive patients (n=176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a one-year period. Direct examination, culture, Aspergillus qPCR (Af-qPCR) and galactomannan was performed on all respiratory samples (n=350). Serum galactomannan, ß-D-glucan and plasma Af-qPCR were also assessed. Criteria were analyzed alone or in combination in relation to mortality rate. Results: Mortality was significantly different in patients with 0, ≤2 and ≥3 positive criteria (logrank test, p=0.04) with death rate of 43.1, 58.1 and 76.4% respectively. Direct examination, plasma qPCR and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46/350) with significantly lower Cq when associated with at least one other criteria (30.2 vs 35.8) (p<0.001). Conclusion: Combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately.

7.
J Clin Med ; 11(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35054133

RESUMO

Acute Heart Failure (AHF)-related hospitalizations and mortality are still high in western countries, especially among older patients. This study aimed to describe the clinical characteristics and predictors of in-hospital mortality of older patients hospitalized with AHF. We conducted a retrospective study including all consecutive patients ≥65 years who were admitted for AHF at a single academic medical center between 1 January 2008 and 31 December 2018. The primary outcome was all-cause, in-hospital mortality. We also analyzed deaths due to cardiovascular (CV) and non-CV causes and compared early in-hospital events. The study included 6930 patients, mean age 81 years, 51% females. The overall mortality rate was 13%. Patients ≥85 years had higher mortality and early death rate than younger patients. Infections were the most common condition precipitating AHF in our cohort, and pneumonia was the most frequent of these. About half of all hospital deaths were due to non-CV causes. After adjusting for confounding factors other than NYHA class at admission, infections were associated with an almost two-fold increased risk of mortality, HR 1.74, 95% CI 1.10-2.71 in patients 65-74 years (p = 0.014); HR 1.83, 95% CI 1.34-2.49 in patients 75-84 years (p = 0.001); HR 1.74, 95% CI 1.24-2.19 in patients ≥85 years (p = 0.001). In conclusion, among older patients with AHF, in-hospital mortality rates increased with increasing age, and infections were associated with an increased risk of in-hospital mortality. In contemporary patients with AHF, along with the treatment of the CV conditions, management should be focused on timely diagnosis and appropriate treatment of non-CV factors, especially pulmonary infections.

9.
Br J Anaesth ; 128(2): 236-243, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34895718

RESUMO

BACKGROUND: The relationship between the dose (volume of fluid) and the effect (increase of stroke volume [SV]) has been poorly described. We hypothesised that the analysis of the dynamic response of SV during fluid challenge (FC) helps to determine the optimal volume of FC, along with its diagnostic accuracy parameters for fluid responsiveness. METHODS: A prospective observational study was conducted in critically ill patients with circulatory failure. Patients monitored with oesophageal Doppler and assigned to an FC of 500 ml of crystalloid were included. The areas under the curve (AUC) and 95% confidence intervals (CI95) of the receiver operating characteristic curves for cumulative volumes from 50 to 450 ml were determined for fluid responsiveness (SV increase ≥15% from baseline) along with other parameters of diagnostic accuracy. In the pharmacodynamic analysis, dose-effect and dose-response models were constructed, with determination of median and 90% effective dose (ED50 and ED90). RESULTS: Forty-five patients were included. The AUC increased with cumulative volumes of FC up to 250 ml (AUC250 0.93 [CI95: 0.85-1.00]), followed by a plateau above 0.95 of AUC. The optimal volume was 250 ml, associated with a specificity of 0.89 [CI95: 0.78-1.00], a sensitivity of 0.92 [CI95: 0.69-1.00], and a threshold of 9.6% increase in SV. The ED50 was 156 [CI95: 136-177] ml and the ED90 was 312 [CI95: 269-352] ml. CONCLUSIONS: A volume of FC of 250 ml with a threshold of 9.6% increase in SV showed the highest accuracy in detecting fluid responsiveness in critically ill patients with shock. CLINICAL TRIAL REGISTRATION: .

10.
J Mycol Med ; 32(1): 101231, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34864498

RESUMO

COVID-19-associated mold infections have been increasingly reported, and the main entity is COVID-19-associated aspergillosis (CAPA). Similarly, COVID-19-associated mucormycosis has been reported in hematology, and its prevalence is high and has been increasing in the diabetic population in India during the third COVID-19 pandemic wave. Simultaneous infection with Mucorales and Aspergillus is rare and even rarer during COVID-19. Here, we report the case of a previously immunocompetent patient with severe SARS-CoV-2 infection complicated with probable CAPA and mucormycosis co-infection. Specific diagnostic tools for mucormycosis are lacking, and this case highlights the advantages of analyzing blood and respiratory samples using the quantitative polymerase chain reaction to detect these fungi. We further reviewed the literature on mixed Aspergillus/Mucorales invasive fungal diseases to provide an overview of patients presenting with both fungi and to identify characteristics of this rare infection.

11.
Heart Fail Rev ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855062

RESUMO

Although more than 90% of children born with congenital heart disease (CHD) survive into adulthood, patients face significantly higher and premature morbidity and mortality. Heart failure as well as non-cardiac comorbidities represent a striking and life-limiting problem with need for new treatment options. Systemic chronic inflammation and immune activation have been identified as crucial drivers of disease causes and progression in various cardiovascular disorders and are promising therapeutic targets. Accumulating evidence indicates an inflammatory state and immune alterations in children and adults with CHD. In this review, we highlight the implications of chronic inflammation, immunity, and immune senescence in CHD. In this context, we summarize the impact of infant open-heart surgery with subsequent thymectomy on the immune system later in life and discuss the potential role of comorbidities and underlying genetic alterations. How an altered immunity and chronic inflammation in CHD influence patient outcomes facing SARS-CoV-2 infection is unclear, but requires special attention, as CHD could represent a population particularly at risk during the COVID-19 pandemic. Concluding remarks address possible clinical implications of immune changes in CHD and consider future immunomodulatory therapies.

12.
Eur J Emerg Med ; 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34954724

RESUMO

BACKGROUND AND IMPORTANCE: An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission. OBJECTIVE: The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED. DESIGN, SETTINGS AND PARTICIPANTS: Consecutive adult patients with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication were collected. Follow-up at 1 year was performed via national data registries. OUTCOMES MEASURE AND ANALYSIS: The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin. MAIN RESULTS: A total of 1455 patients were included with 43% of women. Compared to men, women were older [median (interquartile range) age 74 (65-80) vs. 68 (59-77) years, P < 0.0001]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53-0.88), P = 0.0028]. CONCLUSION: Women have a better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve gender equality in health.

13.
Anaesth Crit Care Pain Med ; 41(1): 101012, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34952218

RESUMO

OBJECTIVE: Limited information is currently available on the impact of vasoactive medications in intensive care (ICU) and long-term outcomes. The main objective of our study was to describe the association between the use of inotropes and/or vasopressors and ICU mortality. Secondary objectives were to evaluate the association between the use of vasoactive drugs and in-hospital as well as 1-year all-cause mortality in ICU survivors. METHODS: FROG-ICU was a prospective, observational, multi-centre cohort designed to investigate long-term mortality of critically ill adult patients. Cox proportional hazards models were used to evaluate the association between the use of inotropes and/or vasopressors and ICU mortality, as well as in-hospital and 1-year all-cause mortality in a propensity-score matched cohort. RESULTS: The study included 2087 patients, 939 of whom received inotropes and/or vasopressors during the initial ICU stay. Patients treated with vasoactive medications were older and had a more severe clinical presentation. In a propensity score-matched cohort of 1201 patients, ICU mortality was higher in patients who received vasoactive medications (HR of 1.40 [1.10-1.78], p = 0.007). One thousand six hundred thirty-five patients survived the index ICU hospitalisation. There was no significant difference according to the use of inotropes and/or vasopressors in the propensity-score matched cohort on in-hospital mortality (HR of 0.94 [0.60-1.49], p = 0.808) as well as one-year all-cause mortality (HR 0.94 [0.71-1.24], p = 0.643). CONCLUSION: Inotropic and/or vasopressor therapy is a strong predictor of in-ICU death. However, the use of inotropes and/or vasopressors during ICU admission was not associated with a worse prognosis after ICU discharge.

14.
Eur J Heart Fail ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34962044

RESUMO

AIMS: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF). METHODS AND RESULTS: Of 5951 participants in the ESC HF Long-Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In-hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post-discharge, events per 100 patient-years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all-cause death 22 (20-24) versus 17 (14-20) versus 17 (15-20); cardiovascular (CV) death 12 (10-13) versus 8.6 (6.6-11) versus 8.4 (6.9-10); non-CV death 2.4 (1.8-3.1) versus 3.3 (2.1-4.8) versus 4.5 (3.5-5.9); all-cause hospitalization 48 (45-51) versus 35 (31-40) versus 42 (39-46); HF hospitalization 29 (27-32) versus 19 (16-22) versus 17 (15-20); and non-CV hospitalization 7.7 (6.6-8.9) versus 9.6 (7.5-12) versus 15 (13-17). CONCLUSION: In AHF, HFrEF is more severe and has greater in-hospital mortality. Post-discharge, HFrEF has greater CV risk, HFpEF greater non-CV risk, and HFmrEF lower overall risk.

15.
Lancet Respir Med ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34895483

RESUMO

BACKGROUND: Cardiogenic shock has a high mortality on optimal therapy. Adrenomedullin is released during cardiogenic shock and is involved in its pathophysiological processes. This study assessed treatment with the humanised, monoclonal, non-neutralising, adrenomedullin antibody adrecizumab, increasing circulating concentrations of adrenomedullin in cardiogenic shock. METHODS: In this investigator-initiated, placebo-controlled, double-blind, multicentre, randomised trial (ACCOST-HH), patients were recruited from four university hospitals in Germany. Patients were eligible if they were 18 years old or older and hospitalised for cardiogenic shock within the last 48 h. Exclusion criteria were resuscitation for longer than 60 min and cardiogenic shock due to sustained ventricular tachycardia or bradycardia. Adult patients in cardiogenic shock were randomly assigned (1:1) to intravenous adrecizumab (8 mg/kg bodyweight) or placebo using an internet-based software. A block randomisation procedure was applied with stratification by age (older vs younger than 65 years), sex (male vs female), and type of underlying cardiogenic shock (acute myocardial infarction vs other entities). Investigators, patients, and medical staff involved in patient care were masked to group assignment. The primary endpoint was number of days up to day 30 without the need for cardiovascular organ support, defined as vasopressor therapy, inotropes, or mechanical circulatory support (or both) assessed in the intention-to-treat population. Safety outcomes included therapy-emergent serious adverse events, severe adverse events, adverse events, suspected unexpected serious adverse reactions, study drug-related mortality, and total mortality. The trial was registered at ClinicalTrials.gov, NCT03989531, and EudraCT, 2018-002824-17, and is now complete. FINDINGS: Between April 5, 2019, and Jan 13, 2021, 150 patients were enrolled: 77 (51%) were randomly assigned to adrecizumab and 73 (49%) to placebo. All patients received the allocated treatment. The number of days without the need for cardiovascular organ support was not different between patients receiving adrecizumab or placebo (12·37 days [95% CI 9·80-14·94] vs 14·05 [11·41-16·69]; adjusted mean difference -1·69 days [-5·37 to 2·00]; p=0·37). Serious adverse events occurred in 59 patients receiving adrecizumab and in 57 receiving placebo (odds ratio 0·92 [95% CI 0·43-1·98]; p=0·83). Mortality was not different between groups at 30 days (hazard ratio 0·99 [95% CI 0·60-1·65]; p=0·98) or 90 days (1·10 [0·68-1·77]; p=0·71). INTERPRETATION: Adrecizumab was well tolerated in patients with cardiogenic shock but did not reduce the need for cardiovascular organ support or improve survival at days 30 and 90. FUNDING: Adrenomed AG and University Hospital of Hamburg.

16.
Burns ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34823946

RESUMO

BACKGROUND: The aim of this study was to describe the prevalence, characteristics and outcome of critically burn patients with pulmonary HSV reactivation. METHODS: Retrospective, single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients with bronchoalveolar lavage performed for pneumoniae suspicion and screened for HSV from January 2013 and April 2017. We used logistic regression to identify factors associated with HSV reactivation and outcomes. RESULTS: 94 patients were included, mean age was 51 (39-64) years; median total body surface area burned was 36 (25-54)% and ICU mortality 38%. Fifty-five patients (59%) had pulmonary HSV reactivation and 30 (55%) were treated with acyclovir. Patients with HSV reactivation were more severely ill with higher SOFA score at admission compared to patient without HSV reactivation (6 [3-8] vs. 2 [1-4], p < 0.0001 respectively). In multivariate analysis, sex, SOFA score at admission and smoke inhalation were significantly associated with HSV reactivation. Only septic shock was associated with 90-day mortality when HSV reactivation was not. CONCLUSIONS: Pulmonary HSV reactivation is frequent among severely ill burn patients. Initial severity and smoke inhalation are risk factors. Antiviral treatment was not associated with outcome.

17.
Eur J Heart Fail ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837447

RESUMO

AIMS: Remote monitoring of pulmonary artery (PA) pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of PA pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross-sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function. METHODS AND RESULTS: Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex-vivo and in-vivo, and then used to measure the cross-sectional area of the IVC. Right and left sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross-sectional area in ex-vivo and in-vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion (p<0.001), vasodilation (p<0.001) and cardiac dysfunction induced by rapid pacing (p≤0.02). CONCLUSIONS: IVC area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure-based monitors in HF. This article is protected by copyright. All rights reserved.

20.
Intensive Care Med ; 47(11): 1284-1294, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34605947

RESUMO

PURPOSE: Investigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin. METHODS: Phase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL, < 12 h of vasopressor start for septic shock were eligible. Randomization was 1:1:2. Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded. Efficacy endpoints included the Sepsis Support Index (SSI, reflecting ventilator- and shock-free days alive), change in Sequential-related Organ Failure Assessment (SOFA) and 28-day mortality. RESULTS: 301 patients were enrolled (median time of 8.5 h after vasopressor start). Adrecizumab was well tolerated (one interruption, no hemodynamic alteration) with no differences in frequency and severity in TEAEs between treatment arms (TEAE of grade 3 or higher: 70.5% in the adrecizumab group and 71.1% in the placebo group) nor in 90-day mortality. Difference in change in SSI between adrecizumab and placebo was 0.72 (CI -1.93-0.49, p = 0.24). Among various secondary endpoints, delta SOFA score (defined as maximum versus minimum SOFA) was more pronounced in the adrecizumab combined group compared to placebo [difference at 0.76 (95% CI 0.18-1.35); p = 0.007]. 28-day mortality in the adrecizumab group was 23.9% and 27.7% in placebo with a hazard ratio of 0.84 (95% confidence interval 0.53-1.31, log-rank p = 0.44). CONCLUSIONS: Overall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients.


Assuntos
Adrenomedulina , Choque Séptico , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores , Método Duplo-Cego , Humanos , Choque Séptico/tratamento farmacológico , Resultado do Tratamento
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