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1.
Crit Care Med ; 49(1): e1-e10, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33337748

RESUMO

OBJECTIVES: The objective of this study was to prospectively evaluate the ability of transthoracic echocardiography to assess pulmonary artery occlusion pressure in mechanically ventilated critically ill patients. DESIGN: In a prospective observational study. SETTING: Amiens University Hospital Medical ICU. PATIENTS: Fifty-three mechanically ventilated patients in sinus rhythm admitted to our ICU. INTERVENTION: Transthoracic echocardiography was performed simultaneously to pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Transmitral early velocity wave recorded using pulsed wave Doppler (E), late transmitral velocity wave recorded using pulsed wave Doppler (A), and deceleration time of E wave were recorded using pulsed Doppler as well as early mitral annulus velocity wave recorded using tissue Doppler imaging (E'). Pulmonary artery occlusion pressure was measured simultaneously using pulmonary artery catheter. There was a significant correlation between pulmonary artery occlusion pressure and lateral ratio between E wave and E' (E/E' ratio) (r = 0.35; p < 0.01), ratio between E wave and A wave (E/A ratio) (r = 0.41; p < 0.002), and deceleration time of E wave (r = -0.34; p < 0.02). E/E' greater than 15 was predictive of pulmonary artery occlusion pressure greater than or equal to 18 mm Hg with a sensitivity of 25% and a specificity of 95%, whereas E/E' less than 7 was predictive of pulmonary artery occlusion pressure less than 18 mm Hg with a sensitivity of 32% and a specificity of 81%. E/A greater than 1.8 yielded a sensitivity of 44% and a specificity of 95% to predict pulmonary artery occlusion pressure greater than or equal to 18 mm Hg, whereas E/A less than 0.7 was predictive of pulmonary artery occlusion pressure less than 18 mm Hg with a sensitivity of 19% and a specificity of 94%. A similar predictive capacity was observed when the analysis was confined to patients with EF less than 50%. A large proportion of E/E' measurements 32 (60%) were situated between the two cut-off values obtained by the receiver operating characteristic curves: E/E' greater than 15 and E/E' less than 7. CONCLUSIONS: In mechanically ventilated critically ill patients, Doppler transthoracic echocardiography indices are highly specific but not sensitive to estimate pulmonary artery occlusion pressure.

2.
Intensive Care Med ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275163

RESUMO

PURPOSE: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies. METHODS: The PRICE panel identified lists of clinical and echocardiographic parameters (the "items") deemed important in four main areas of CCE research: left ventricular systolic and diastolic functions, right ventricular function and fluid management. Each item was graded using a critical index (CI) that combined the relative importance of each item and the fraction of studies that did not report it, also taking experts' opinion into account. RESULTS: A list of items in each area that deemed essential for the proper interpretation and application of research results is recommended. Additional items which aid interpretation were also proposed. CONCLUSION: The PRICES recommendations reported in this document, as a checklist, represent an international consensus of experts as to which parameters and information should be included in the design of echocardiography research studies. PRICES recommendations provide guidance to scientists in the field of CCE with the objective of providing a recommended framework for reporting of CCE methodology and results.

3.
Lancet Neurol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212063

RESUMO

BACKGROUND: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. METHODS: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. FINDINGS: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. INTERPRETATION: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran. FUNDING: Alnylam Pharmaceuticals.

4.
Ann Intensive Care ; 10(1): 118, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894389

RESUMO

The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emergency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Intensivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheter-related infections' prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2- adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed definitions, and therapeutic strategies.

5.
Crit Care Med ; 48(10): e943-e950, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32885942

RESUMO

OBJECTIVES: Evaluation of left atrial pressure is frequently required for mechanically ventilated critically ill patients. The objective of the present study was to evaluate the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for assessment of the pulmonary artery occlusion pressure (a frequent surrogate of left atrial pressure) in this population. DESIGN: A pooled analysis of three prospective cohorts of patients simultaneously assessed with a pulmonary artery catheter and echocardiography. SETTINGS: Medical-surgical intensive care department of two university hospitals in France. PATIENTS: Mechanically ventilated critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 98 included patients (males: 67%; mean ± SD age: 59 ± 16; and mean Simplified Acute Physiology Score 2: 54 ± 20), 53 (54%) experienced septic shock. Using the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, the predicted pulmonary artery occlusion pressure was indeterminate in 48 of the 98 patients (49%). Of the 24 patients with an elevated predicted left atrial pressure (grade II/III diastolic dysfunction), only 17 (71%) had a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg. Similarly, 20 of the 26 patients (77%) with a normal predicted left atrial pressure (grade I diastolic dysfunction) had a measured pulmonary artery occlusion pressure less than 18 mm Hg. The sensitivity and specificity of American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for predicting elevated pulmonary artery occlusion pressure were both 74%. The agreement between echocardiography and the pulmonary artery catheter was moderate (Cohen's Kappa, 0.48; 95% CI, 0.39-0.70). In a proposed alternative algorithm, the best echocardiographic predictors of a normal pulmonary artery occlusion pressure were a lateral e'-wave greater than 8 (for a left ventricular ejection fraction ≥ 45%) or an E/A ratio less than or equal to 1.5 (for a left ventricular ejection fraction < 45%). CONCLUSIONS: The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines do not accurately assess pulmonary artery occlusion pressure in ventilated critically ill patients. Simple Doppler measurements gave a similar level of diagnostic performance with less uncertainly.

6.
Ann. intensive care ; 118: 1-26, Sept. 07, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1128263

RESUMO

The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emer­ gency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Inten­ sivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheterrelated infections' prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2− adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed defnitions, and therapeutic strategies.


Assuntos
Humanos , Adulto , Controle de Infecções/métodos , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/transmissão , Clorexidina/uso terapêutico , Medicina Baseada em Evidências , Unidades de Terapia Intensiva/normas
8.
Curr Opin Neurol ; 33(5): 553-561, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32796279

RESUMO

PURPOSE OF REVIEW: Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant, life-threatening disease. Until recently only early stages of ATTRv-PN (polyneuropathy) had access to disease-modifying therapy (DMT), whereas there was no specific treatment for ATTRv-CM (cardiomyopathy). This review updates our knowledge about results of three phase 3 clinical trials, expert's consensus for early diagnosis and emerging biomarkers. RECENT FINDINGS: Two phase 3 studies using RNAi and antisense oligonucleotides (ASO) were successful. Primary endpoints were progression of neuropathic score mNIS +7 and quality of Life (QOL) in a population of ATTRv-PN at different levels of severity. They knock downed circulating amyloidogenic mutant and wild-type TTR. Safety concerned ASO with a risk of thrombocytopenia. RNAi showed possible reversibility of the disease. Phase 3 ATTRACT trial-tested tafamidis versus placebo in patients with ATTRv-CM and ATTRwt-CM and showed a significant reduction of all-cause mortality and rates of cardiovascular-related hospitalizations. All three drugs obtained marketing authorization by European Medicines Agency (EMA) and Food and drug administration (FDA). Early diagnosis criteria for ATTRv-PN and ATTRv-CM are available. Ongoing clinical trials for ATTRv are presented. New biomarkers are plasma neurofilament light chain, intraepidermal nerve fiber density. SUMMARY: The majority of patients with ATTRv may have now access to a DMT. Criteria for early diagnosis are available.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32531040

RESUMO

AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

10.
Am J Respir Crit Care Med ; 202(5): 708-716, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407157

RESUMO

Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-ß-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P < 0.0001, P = 0.003, and P = 0.008, respectively).Conclusions: ITBA was associated with higher severity scores, mortality, and serum and BAL fluid galactomannan and 1,3-ß-d-glucan concentrations than invasive pulmonary aspergillosis without tracheobronchial lesions. ITBA should be systematically researched by bronchoscopic examination in ICU patients with concomitant pulmonary aspergillosis and influenza.Clinical trial registered with www.clinicaltrials.gov (NCT04077697).


Assuntos
Antifúngicos/uso terapêutico , Estado Terminal , Hospedeiro Imunocomprometido , Influenza Humana/complicações , Aspergilose Pulmonar Invasiva/etiologia , Idoso , Aspergillus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
11.
Br J Ophthalmol ; 104(10): 1363-1367, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31949094

RESUMO

AIMS: To investigate the relationship between the ophthalmic and systemic phenotypes in patients with hereditary transthyretin amyloidosis with the S77Y mutation (ATTRS77Y). METHODS: In this cross-sectional study, patients with genetically confirmed ATTRS77Y amyloidosis were enrolled. All patients underwent complete neurological examination, including staging with the Neuropathy Impairment Score (NIS), Polyneuropathy Disability (PND) score; complete cardiological evaluation, including echocardiography, cardiac MRI and/or cardiac scintigraphy and complete ophthalmic evaluation, including slit lamp examination and fundus examination. Ocular ancillary tests (fluorescein and indocyanine green angiography, and anterior segment optical coherence tomography) were performed in cases with abnormal findings. The Kruskal-Wallis test was used for quantitative outcomes and Fisher's exact test for qualitative outcomes. Statistical significance was indicated by p<0.05 (two tailed). RESULTS: The study sample was composed of 24 ATTRS77Y patients. The mean patient age was 58.4±12.4 years. None of the patients presented with amyloid deposits in the anterior chamber, secondary glaucoma or vitreous amyloidosis. Retinal angiopathy was observed in four patients, complicated with retinal ischaemia in one patient. Conjunctival lymphangiectasia (CL) was detected in 13 patients (54%), associated with perilymphatic amyloid deposits. The presence of CL was statistically associated with more severe neurological disease (NIS=43.3±31.9 vs 18.9±20.4; PND=2.6±1.0 vs 1.4±0.7 in patients with and without CL, respectively; both p<0.05) and amyloid cardiomyopathy (p=0.002). CONCLUSION: In ATTRS77Y patients, CL is common and could serve as a potential biomarker for severe systemic disease. There were neither anterior chamber deposits, secondary glaucoma nor vitreous deposits in ATTRS77Y patients.

12.
Arch Cardiovasc Dis ; 112(8-9): 469-484, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31262635

RESUMO

BACKGROUND: Current drug-eluting stents (c-DESs) reduce the occurrence of ischaemic events, but expose recipients to stent thrombosis and bleeding secondary to preventive antiplatelet therapy. To date, comparative data on the relative effectiveness and safety of the various c-DESs in real life are limited. AIM: To compare ischaemic and bleeding risks across the major c-DESs used in France. METHODS: French national health insurance reimbursement and hospitalization databases were used. Patients implanted with a c-DES in 2014 were followed for 1 year. The risks of ischaemic events (revascularization, myocardial infarction and/or stroke), major bleeding events and death were compared across six c-DESs (XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® and ORSIRO®), using multilevel Cox models adjusted for baseline individual and hospital characteristics. RESULTS: A total of 52,891 subjects were included: 34.4% with XIENCE®; 27.6% with PROMUS®; 24.0% with RESOLUTE®; 8.0% with BIOMATRIX®; 5.0% with NOBORI®; and 1.0% with ORSIRO®. Among them, 9378 had at least one event (ischaemic, 6064; major bleeding, 1968; death, 2411), resulting in an overall incidence rate of 19 per 100 person-years. In the multivariable analysis, the risk of ischaemic events, major bleeding events or death did not differ between the c-DESs overall (adjusted hazard ratios between 0.85 [95% confidence interval 0.68-1.07] and 1.04 [95% confidence interval 0.98-1.10] compared with XIENCE® used as the reference) and when each outcome was considered separately. CONCLUSIONS: In real life, major ischaemic and bleeding risks do not differ across the various c-DESs over the first year following implantation. Future studies are needed to assess comparative c-DES effectiveness and safety longer term.


Assuntos
Doença da Artéria Coronariana/terapia , Trombose Coronária/epidemiologia , Stents Farmacológicos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/mortalidade , Bases de Dados Factuais , Feminino , França/epidemiologia , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Desenho de Prótese , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Crit Care ; 23(1): 257, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315648

RESUMO

BACKGROUND: Diagnosis of significant coronary artery disease (CAD) and acute coronary artery occlusion in ICU can be difficult, and an inappropriate intervention is potentially harmful. Myocardial contrast perfusion echo (MCPE) examines ultrasound contrast intensity replenishment curves in individual myocardial segments measuring peak contrast intensity and slope of return as an index of myocardial blood flow (units = intensity of ultrasound per second [dB/s]). MCPE could possibly serve as a triage tool to invasive angiography by estimating blood flow in the myocardium. We sought to assess feasibility in the critically ill and if MCPE could add incremental value to the clinical acumen in predicting significant CAD. METHODS: This is a single-centre, prospective, observational study. Inclusion criteria were as follows: adult ICU patients with troponin I > 50 ng/L and cardiology referral being made for consideration of inpatient angiography. Exclusion criteria were as follows: poor echo windows (2 patients), known ischaemic heart disease, and contrast contraindications. Seven cardiologists and 6 intensivists blinded to outcome assessed medical history, ECG, troponin, and 2D echo images to estimate likelihood of significant CAD needing intervention (clinical acumen). Clinical acumen, quantitative MCPE, and subjective (visual) MCPE were assessed to predict significant CAD. RESULTS: Forty patients underwent MCPE analysis, 6 (15%) had significant CAD, and median 11 of 16 segments (IQR 8-13) could be imaged (68.8% [IQR 50-81]). No adverse events occurred. A significant difference was found in overall MCPE blood flow estimation between those diagnosed with significant CAD and those without (3.3 vs 2.4 dB/s, p = 0.050). A MCPE value of 2.8 dB/s had 67% sensitivity and 88% specificity in detecting significant CAD. Clinical acumen showed no association in prediction of CAD (OR 0.6, p = 0.09); however, if quantitative or visual MCPE analysis was included, a significant association occurred (OR 17.1, p = 0.01; OR 23.0, p = 0.01 respectively). CONCLUSIONS: MCPE is feasible in the critically ill and shows better association with predicting significant CAD vs clinical acumen alone. MCPE adds incremental value to initial assessment of the presence of significant CAD which may help guide those who require urgent angiography.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Ecocardiografia/métodos , Perfusão/normas , Adulto , Idoso , Meios de Contraste/uso terapêutico , Doença da Artéria Coronariana/fisiopatologia , Ecocardiografia/normas , Estudos de Viabilidade , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , New South Wales , Perfusão/estatística & dados numéricos , Estudos Prospectivos , Troponina I/análise , Troponina I/sangue
14.
Nat Rev Neurol ; 15(7): 387-404, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209302

RESUMO

Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis with polyneuropathy (also known as familial amyloid polyneuropathy) is a condition with adult onset caused by mutation of transthyretin (TTR) and characterized by extracellular deposition of amyloid and destruction of the somatic and autonomic PNS, leading to loss of autonomy and death. This disease represents a model of the scientific and medical progress of the past 30 years. ATTRv amyloidosis is a worldwide disease with broad genetic and phenotypic heterogeneity that presents a diagnostic challenge for neurologists. The pathophysiology of the neuropathy is increasingly understood and includes instability and proteolysis of mutant TTR leading to deposition of amyloid with variable lengths of fibrils, microangiopathy and involvement of Schwann cells. Wild-type TTR is amyloidogenic in older individuals. The main symptoms are neuropathic, but the disease is systemic; neurologists should be aware of cardiac, eye and kidney involvement that justify a multidisciplinary approach to management. Infiltrative cardiomyopathy is usually latent but present in half of patients. Disease-modifying therapeutics that have been developed include liver transplantation and TTR stabilizers, both of which can slow progression of the disease and increase survival in the early stages. Most recently, gene-silencing drugs have been used to control disease in the more advanced stages and produce some degree of improvement.


Assuntos
Neuropatias Amiloides Familiares/genética , Pré-Albumina/genética , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Amiloides Familiares/patologia , Progressão da Doença , Humanos , Mutação , Células de Schwann/patologia
15.
Resuscitation ; 141: 104-110, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31216431

RESUMO

AIM: To determine whether the urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can identify patients who will develop severe acute kidney injury (AKI) soon after cardiac arrest. METHODS: We performed a prospective, multicentre study in three French ICUs. The performance of [TIMP-2]*[IGFBP7] was assessed for urine samples collected a median [IQR] of 240 [169-315] minutes post-collapse. The primary end-point was severe AKI (KDIGO stage 3), within 48 h of admission. RESULTS: Of the 115 patients analyzed, 32 (28%) developed severe AKI. Eleven of these required renal replacement therapy. The median [IQR] baseline [TIMP-2]*[IGFBP7] level was higher in patients who developed severe AKI (1.57 [0.80-6.62] (ng/ml)2/1000) than in those who did not (0.17 [0.05-0.59] (ng/ml)2/1000; p < 0.001). The baseline [TIMP2]*[IGFBP7] predicted -severe AKI with an area under the curve [95% confidence interval (CI)] of 0.91 [0.84-0.95], an optimal cut-off value of 0.39 (ng/ml)2/1000, a sensitivity [95%CI] of 97% [84-100], and a specificity of 72% [61-82]. A cut-off of 2.0 (ng/ml)2/1000 yielded a specificity of 98% [92-100]. For predicting severe AKI, baseline [TIMP-2]*[IGFBP7] was significantly more discriminant than baseline SCr (AUC [95%CI]: 0.73 [0.63-0.84]; p = 0.005), and slightly but not significantly more discriminant than baseline UO (AUC [95%CI]: 0.86 [0.78‒0.94], p = 0.08) Combining the baseline [TIMP2]*[IGFBP7] with baseline SCr and UO significantly improved the latter markers' predictive performance. CONCLUSION: Urine [TIMP-2]*[IGFBP7] effectively identify patients with a risk of severe AKI. Below a cut-off of 0.39 (ng/ml)2/1000, the risk of severe AKI is low.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Parada Cardíaca/complicações , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de Doença
16.
Dis Markers ; 2019: 3471215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061681

RESUMO

Background: To examine whether the new urinary biomarkers TIMP2 and IGFBP7 can predict progression within 24 hours and 72 hours from mild and moderate (KDIGO 1 or 2) to severe (KDIGO 3) AKI in patients with septic shock. Methods: A prospective, multicenter observational study performed in three French ICUs. The urinary biomarkers TIMP2∗IGFBP7 were analyzed at the early phase (<6 hours) of patients admitted for septic shock with mild and moderate AKI. Results: Among the 112 patients included, 45 (40%) progressed to the KDIGO 3 level 24 hours after inclusion (KDIGO 3 H24) and 47 (42%) 72 hours after inclusion (KDIGO 3 H72). The median urinary TIMP2∗IGFBP7 at inclusion (baseline) were higher in the KDIGO 3 group than in the KDIGO<3 group at H24 and H72. All covariates with a p value < 0.1 in the univariate analysis were included in stepwise multiple logistic regression models to identify factors independently associated with the risk of KDIGO 3 at H24 and H72. TIMP2∗IGFBP7 remained independently associated with KDIGO 3 at H24 and H72. Baseline posology of norepinephrine, baseline urine output, and baseline serum creatinine remained also significantly associated with progression to KDIGO 3 at H24. Baseline TIMP2∗IGFBP7 and baseline urinary output had the best AUC ROC. A baseline TIMP2∗IGFBP7 > 2.0 (ng/ml)2/1,000 identified the population at high risk of KDIGO 3 H24 (relative risk 4.19 (1.7-10.4)) with a sensitivity of 76% (60-87) and a specificity of 81% (69-89). But the diagnostic performance at H72 of baseline TIMP2∗IGFBP7 was poor (AUC: 0.69 (0.59-0.77)). Conclusion: The urinary TIMP2∗IGFBP7 concentration and the urine output at the early phase of septic shock are independent factors to identify the population at high risk of progression from mild and moderate to severe AKI over the next 24 but not 72 hours. A TIMP2∗IGFBP7 concentration > 2.0 (ng/ml)2/1,000 quadruples the risk of KDIGO 3 AKI within 24 hours. This trial is registered with (NCT03547414).


Assuntos
Lesão Renal Aguda/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Choque Séptico/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Lesão Renal Aguda/complicações , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Choque Séptico/etiologia
17.
Crit Care ; 23(1): 70, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845976

RESUMO

BACKGROUND: Right ventricle (RV) size and function assessment by echocardiography (echo) is a standard tool in the ICU. Frequently subjective assessment is performed, and guidelines suggest its utility in adequately trained clinicians. We aimed to compare subjective (visual) assessment of RV size and function by ICU physicians, with advanced qualifications in echocardiography, vs objective measurements. METHODS: ICU specialists with a qualification in advanced echocardiography reviewed 2D echo clips from critically ill patients on mechanical ventilation with PaO2:FiO2 < 300. Subjective assessments of RV size and function were made independently using a three-class categorical scale. Agreement (B-score) and bias (p value) were analysed using objective echo measurements. RV size assessment included RV end-diastolic area (EDA) and diameters. RV function assessment included fractional area change, S', TAPSE and RV free wall strain. Binary and ordinal analysis was performed. RESULTS: Fifty-two clinicians reviewed 2D images from 80 patients. Fair agreement was seen with objective measures vs binary assessment of RV size (RV EDA 0.26 [p < 0.001], RV dimensions 0.29 [p = 0.06]) and function (RV free wall strain 0.27 [p < 0.001], TAPSE 0.27 [p < 0.001], S' 0.29 [p < 0.001], FAC 0.31 [p = 0.16]). However, ordinal data analysis showed poor agreement with RV dimensions (0.11 [p = 0.06]) and RV free wall strain (0.14 [p = 0.16]). If one-step disagreement was allowed, agreement was good (RV dimensions 0.6 [p = 0.06], RV free wall strain 0.6 [p = 0.16]). Significant overestimation of severity of abnormalities was seen with subjective assessment vs RV EDA, TAPSE, S' and fractional area change. CONCLUSION: Subjective (visual) assessment of RV size and function, by ICU specialists trained in advanced echo, can be fairly reliable for the initial exclusion of significant RV pathology. It seems prudent to avoid subjective RV assessment in isolation.


Assuntos
Competência Clínica/normas , Ecocardiografia/normas , Ventrículos do Coração/fisiopatologia , Função Ventricular Direita/fisiologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Cuidados Críticos/métodos , Autoavaliação Diagnóstica , Ecocardiografia/métodos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Médicos/normas , Médicos/estatística & dados numéricos , Reprodutibilidade dos Testes
19.
JAMA Cardiol ; 4(5): 466-472, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878017

RESUMO

Importance: Patients with cardiac amyloidosis demonstrate reduced myocardial strain with associated sparing of the cardiac apex. In the APOLLO randomized clinical trial, patisiran, an RNA interference therapeutic that inhibits transthyretin synthesis, improved left ventricular (LV) global longitudinal strain (LV GLS) compared with placebo in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy and evidence of cardiac involvement. Objective: To evaluate the treatment association of patisiran with regional LV myocardial strain in cardiac manifestation in hATTR amyloidosis. Design, Setting, and Participants: This exploratory analysis of APOLLO, a randomized, double-blind, placebo-controlled, phase 3, multicenter international clinical trial that was conducted from December 2013 to January 2016, included patients with hATTR amyloidosis with polyneuropathy who were randomized 2:1 to receive patisiran or placebo. The prespecified cardiac subpopulation (126 of 225 [56%]) comprised patients with a baseline LV wall thickness of 13 mm or more and no history of hypertension or aortic valve disease. This post hoc data analysis was performed between September 2018 and January 2019. Intervention: Placebo or patisiran, 0.3 mg/kg, via intravenous infusion once every 3 weeks for 18 months. Main Outcomes and Measures: The association of patisiran with LV regional longitudinal strain at 18 months. Results: Of the 126 patients included in the prespecified cardiac subpopulation, 36 patients (28.6%) received placebo (median [interquartile range] age, 62 [57-72] years) and 90 patients (71.4%) received patisiran (median [interquartile range] age, 60 [54-66] years); 98 (77.8%) were men, 28 (22.2%) were from North America, and 43 (34.1%) were from Western Europe. At baseline, LV GLS was impaired and regional longitudinal strains were lowest in the basal segments with apical sparing. There were no differences in regional longitudinal strains between the treatment groups at baseline. Patisiran improved the absolute GLS (least-squares mean [SE] difference, 1.4% [0.6%]; 95% CI, 0.3%-2.5%; P = .02) compared with placebo at 18 months, with the greatest differential increase observed in the basal region (overall least-squares mean [SE] difference, 2.1% [0.8%]; 95% CI, 0.6%-3.6%; P = .006) and no significant differences in the mid and apical regions among groups. Conclusions and Relevance: Patisiran prevented the deterioration of LV GLS over 18 months, driven primarily by attenuating disease progression in the basal region, suggesting that basal longitudinal strain may be a more sensitive marker of treatment associations with the cardiac manifestation in hATTR amyloidosis and that basal region may be influenced by disease-modifying therapies more than other ventricular regions. Trial Registration: ClinicalTrials.gov identifier: NCT01960348.


Assuntos
Neuropatias Amiloides Familiares/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico , Idoso , Neuropatias Amiloides Familiares/complicações , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Miocárdio , América do Norte/epidemiologia , Placebos/administração & dosagem , Polineuropatias/etiologia , Pré-Albumina/efeitos dos fármacos , Pré-Albumina/genética , RNA Interferente Pequeno/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos
20.
Acta Anaesthesiol Scand ; 63(5): 594-600, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30648262

RESUMO

BACKGROUND: The distending intravascular pressure at no flow conditions reflects the stressed volume. While this haemodynamic variable is recognised as clinically important, there is a paucity of reports of its range and responsiveness to volume expansion in patients without cardiovascular disease and no reports of correlations to echocardiographic assessments of left ventricular filling. METHODS: Twenty-seven awake (13 male), spontaneously breathing patients without any history of cardiopulmonary, vascular or renal disease were studied prior to induction of anaesthesia. The no-flow equilibrium pressure in the arm following rapid circulatory occlusion (Parm ) was measured via a radial arterial catheter. Transthoracic echocardiography was used to measure left ventricular end diastolic area and volume as well as the diameter of the inferior vena cava. The Parm and echocardiographic variables were measured before and after administration of 500 mL 0.9% NaCl over 10 minutes. Changes were analysed by paired t test, Pearson's correlation and multiple linear regression. RESULTS: Parm increased overall from 22 ± 5 mm Hg to 25 ± 6 mm Hg (mean difference 3.0 ± 4.5 mm Hg, P = 0.002) following the fluid bolus with corresponding increases in arterial pressure and echocardiographic variables. Variability in the direction of the Parm response reflected concomitant changes in vascular compliance. Only weak correlations were observed between changes in Parm and inferior vena cava diameter indexed to body surface area (R2  = 0.29, P = 0.01). CONCLUSION: Preoperative measurements of Parm increased following acute expansion of the intravascular volume. Echocardiography demonstrated poor correlation with Parm .


Assuntos
Ecocardiografia , Hidratação , Artéria Radial/fisiologia , Adulto , Pressão Arterial/fisiologia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Prospectivos , Veia Cava Inferior/fisiologia
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