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1.
Acta Cardiol ; 79(2): 109-113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37823390

RESUMO

Takotsubo syndrome (TTS) is a transient left ventricle dysfunction usually caused by a stressful trigger (emotional or physical). We report the case of a 77 year-old female patient who presented with TTS caused by a pheochromocytoma, a catecholamine-producing neuroendocrine tumour. Diagnosis was facilitated by acute kidney injury prompting renal ultrasound, recurrence of TTS and symptoms of episodic palpitations, profuse sweating and labile blood pressure. Furthermore, during her hospitalisation the patient also developed an Ogilvie syndrome, an acute colonic pseudo-obstruction, due to the catecholamine-excess. Treatment consisted of betablocker and angiotensin-converting enzyme inhibitor for TTS, neostigmine for Ogilvie syndrome, in combination with alpha-blocker and surgical removal of the tumour after recuperation of left ventricular function and colonic pseudo-obstruction. To our knowledge, this is the first case report of the pathophysiological triad of pheochromocytoma leading to Takotsubo and Ogilvie syndrome in a single patient.


Assuntos
Neoplasias das Glândulas Suprarrenais , Pseudo-Obstrução do Colo , Feocromocitoma , Cardiomiopatia de Takotsubo , Feminino , Humanos , Idoso , Pseudo-Obstrução do Colo/etiologia , Pseudo-Obstrução do Colo/complicações , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/etiologia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Catecolaminas
2.
EBioMedicine ; 80: 104057, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35584557

RESUMO

BACKGROUND: Reduced glucocorticoid-receptor (GR) expression in blood suggested that critically ill patients become glucocorticoid-resistant necessitating stress-doses of glucocorticoids. We hypothesised that critical illness evokes a tissue-specific, time-dependent expression of regulators of GR-action which adaptively guides glucocorticoid action to sites of need. METHODS: We performed a prospective, observational, cross-sectional human study and two translational mouse studies. In freshly-isolated neutrophils and monocytes and in skeletal muscle and subcutaneous adipose tissue of 137 critically ill patients and 20 healthy controls and in skeletal muscle and adipose tissue as well as in vital tissues (heart, lung, diaphragm, liver, kidney) of 88 septic and 26 healthy mice, we quantified gene expression of cortisone-reductase 11ß-HSD1, glucocorticoid-receptor-isoforms GRα and GRß, GRα-sensitivity-regulating-co-chaperone FKBP51, and GR-action-marker GILZ. Expression profiles were compared in relation to illness-duration and systemic-glucocorticoid-availability. FINDINGS: In patients' neutrophils, GRα and GILZ were substantially suppressed (p≤0·05) throughout intensive care unit (ICU)-stay, while in monocytes low/normal GRα coincided with increased GILZ (p≤0·05). FKBP51 was increased transiently (neutrophils) or always (monocytes,p≤0·05). In patients' muscle, 11ß-HSD1 and GRα were low-normal (p≤0·05) and substantially suppressed in adipose tissue (p≤0·05); FKBP51 and GILZ were increased in skeletal muscle (p≤0·05) but normal in adipose tissue. GRß was undetectable. Increasing systemic glucocorticoid availability in patients independently associated with further suppressed muscle 11ß-HSD1 and GRα, further increased FKBP51 and unaltered GILZ (p≤0·05). In septic mouse heart and lung, 11ß-HSD1, FKBP51 and GILZ were always high (p≤0·01). In heart, GRα was suppressed (p≤0·05), while normal or high in lung (all p≤0·05). In diaphragm, 11ß-HSD1 was high/normal, GRα low/normal and FKBP51 and GILZ high (p≤0·01). In kidney, 11ß-HSD1 transiently increased but decreased thereafter, GRα was normal and FKBP51 and GILZ high (p≤0·01). In liver, 11ß-HSD1 was suppressed (p≤0·01), GRα normal and FKBP51 high (p≤0·01) whereas GILZ was transiently decreased but elevated thereafter (p≤0·05). Only in lung and diaphragm, treatment with hydrocortisone further increased GILZ. INTERPRETATION: Tissue-specific, time-independent adaptations to critical illness guided GR-action predominantly to vital tissues such as lung, while (partially) protecting against collateral harm in other cells and tissues, such as neutrophils. These findings argue against maladaptive generalised glucocorticoid-resistance necessitating glucocorticoid-treatment. FUNDING: Research-Foundation-Flanders, Methusalem-Program-Flemish-Government, European-Research-Council, European-Respiratory-Society.


Assuntos
Glucocorticoides , Receptores de Glucocorticoides , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Animais , Estado Terminal , Estudos Transversais , Expressão Gênica , Humanos , Camundongos , Estudos Prospectivos , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
3.
Intensive Care Med ; 47(12): 1462-1471, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34750648

RESUMO

PURPOSE: To evaluate aerobic exercise capacity in 5-year intensive care unit (ICU) survivors and to assess the association between severity of organ failure in ICU and exercise capacity up to 5-year follow-up. METHODS: Secondary analysis of the EPaNIC follow-up cohort (NCT00512122) including 433 patients screened with cardiopulmonary exercise testing (CPET) between 1 and 5 years following ICU admission. Exercise capacity in 5-year ICU survivors (N = 361) was referenced to a historic sedentary population and further compared to demographically matched controls (N = 49). In 5-year ICU survivors performing a maximal CPET (respiratory exchange ratio > 1.05, N = 313), abnormal exercise capacity was defined as peak oxygen consumption (VO2peak) < 85% of predicted peak oxygen consumption (%predVO2peak), based on the historic sedentary population. Exercise liming factors were identified. To study the association between severity of organ failure, quantified as the maximal Sequential Organ Failure Assessment score during ICU-stay (SOFA-max), and exercise capacity as assessed with VO2peak, a linear mixed model was built, adjusting for predefined confounders and including all follow-up CPET studies. RESULTS: Exercise capacity was abnormal in 118/313 (37.7%) 5-year survivors versus 1/48 (2.1%) controls with a maximal CPET, p < 0.001. Aerobic exercise capacity was lower in 5-year survivors than in controls (VO2peak: 24.0 ± 9.7 ml/min/kg versus 31.7 ± 8.4 ml/min/kg, p < 0.001; %predVO2peak: 94% ± 31% versus 123% ± 25%, p < 0.001). Muscular limitation frequently contributed to impaired exercise capacity at 5-year [71/118 (60.2%)]. SOFA-max independently associated with VO2peak throughout follow-up. CONCLUSIONS: Critical illness survivors often display abnormal aerobic exercise capacity, frequently involving muscular limitation. Severity of organ failure throughout the ICU stay independently associates with these impairments.


Assuntos
Estado Terminal , Tolerância ao Exercício , Exercício Físico , Seguimentos , Humanos , Consumo de Oxigênio , Sobreviventes
4.
Clin Transl Immunology ; 10(4): e1271, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968405

RESUMO

OBJECTIVES: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation. METHODS: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils. RESULTS: Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils. CONCLUSION: Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.

5.
Thorax ; 76(6): 561-567, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33712505

RESUMO

PURPOSE: To assess the association between respiratory muscle weakness (RMW) at intensive care unit (ICU) discharge and 5-year mortality and morbidity, independent from confounders including peripheral muscle strength. METHODS: Secondary analysis of the prospective 5-year follow-up of the EPaNIC cohort (ClinicalTrials.gov: NCT00512122), limited to 366 patients screened for respiratory and peripheral muscle strength in the ICU with maximal inspiratory pressure (MIP) after removal of the artificial airway, and the Medical Research Council sum score. RMW was defined as an absolute value of MIP <30 cmH2O. Associations between RMW at (or closest to) ICU discharge and all-cause 5-year mortality, and key measures of 5-year physical function, comprising respiratory muscle strength (MIP), hand-grip strength (HGF), 6 min walk distance (6MWD) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36), were assessed with Cox proportional hazards and linear regression models, adjusted for confounders including peripheral muscle strength. RESULTS: RMW was present in 136/366 (37.2%) patients at ICU discharge. RMW was not independently associated with 5-year mortality (HR with 95% CI 1.273 (0.751 to 1.943), p=0.352). Among 156five-year survivors, those with, as compared with those without RMW demonstrated worse physical function (MIP (absolute value, cmH2O): 62(42-77) vs 94(78-109), p<0.001; HGF (%pred): 67(44-87) vs 96(68-110), p<0.001; 6MWD (%pred): 87(74-102) vs 99 (80-111), p=0.009; PF-SF-36 (score): 55 (30-80) vs 80 (55-95), p<0.001). Associations between RMW and morbidity endpoints remained significant after adjustment for confounders (effect size with 95% CI: MIP: -23.858 (-32.097 to -15.027), p=0.001; HGF: -18.591 (-30.941 to -5.744), p=0.001; 6MWD (transformed): -1587.007 (-3073.763 to -179.253), p=0.034; PF-SF-36 (transformed): 1.176 (0.144-2.270), p=0.036). CONCLUSIONS: RMW at ICU discharge is independently associated with 5-year morbidity but not 5-year mortality.


Assuntos
Cuidados Críticos/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Força Muscular/fisiologia , Debilidade Muscular/fisiopatologia , Alta do Paciente/tendências , Insuficiência Respiratória/terapia , Músculos Respiratórios/fisiopatologia , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Insuficiência Respiratória/complicações , Insuficiência Respiratória/fisiopatologia , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo
8.
Intensive Care Med ; 46(6): 1184-1193, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31970446

RESUMO

PURPOSE: To assess the independent association between ICU-acquired neuromuscular complications and 5-year mortality and morbidity. To explore the optimal threshold of the Medical Research Council (MRC) sum score, assessing weakness, for the prediction of 5-year outcomes. METHODS: Sub-analyses of a prospective, 5-year follow-up study including 883 EPaNIC patients (Early versus Late Parenteral Nutrition in Intensive Care) (Clinicaltrials.gov:NCT00512122), systematically screened in ICU for neuromuscular complications with MRC sum score ('MRC-cohort', N = 600), electrophysiology on day 8 ± 1 to quantify compound muscle action potential ('CMAP-cohort', N = 689), or both ('MRC&CMAP-cohort', N = 415). Associations between ICU-acquired neuromuscular complications and 5-year mortality, hand-grip strength (HGF, %predicted), 6-min-walk distance (6-MWD, %predicted) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36) at 5-years were assessed with Cox regression and linear regression, adjusted for confounders. The optimal threshold for MRC at ICU discharge to predict 5-year outcomes was determined by martingale residual plots (survival) and scatterplots (morbidity). RESULTS: Both lower MRC sum score at ICU discharge, indicating less strength [HR, per-point-increase: 0.946 (95% CI 0.928-0.968), p = 0.001], and abnormal CMAP, indicating nerve/muscle dysfunction [HR: 1.568 (95% CI 1.165-2.186), p = 0.004], independently associated with increased 5-year mortality. In the MRC&CMAP-cohort, MRC [HR: 0.956 (95% CI 0.934-0.980), p = 0.001] but not CMAP [HR: 1.478 (95% CI 0.875-2.838), p = 0.088] independently associated with 5-year mortality. Among 205 survivors, low MRC independently associated with low HGF [0.866 (95% CI 0.237-1.527), p = 0.004], low 6-MWD [105.1 (95% CI 12.1-212.9), p = 0.043] and low PF-SF-36 [- 0.119 (95% CI - 0.186 to - 0.057), p = 0.002], whereas abnormal CMAP did not correlate with these morbidity endpoints. Exploratory analyses suggested that MRC ≤ 55 best predicted poor long-term morbidity and mortality. Both MRC ≤ 55 and abnormal CMAP independently associated with 5-year mortality. CONCLUSIONS: ICU-acquired neuromuscular complications may impact 5-year morbidity and mortality. MRC sum score, even if slightly reduced, may affect long-term mortality, strength, functional capacity and physical function, whereas abnormal CMAP only related to long-term mortality.


Assuntos
Unidades de Terapia Intensiva , Debilidade Muscular , Cuidados Críticos , Estado Terminal , Seguimentos , Humanos , Debilidade Muscular/epidemiologia , Debilidade Muscular/etiologia , Estudos Prospectivos
9.
Thorax ; 74(11): 1037-1045, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31481633

RESUMO

PURPOSE: Long-term outcomes of critical illness may be affected by duration of critical illness and intensive care. We aimed to investigate differences in mortality and morbidity after short (<8 days) and prolonged (≥8 days) intensive care unit (ICU) stay. METHODS: Former EPaNIC-trial patients were included in this preplanned prospective cohort, 5-year follow-up study. Mortality was assessed in all. For morbidity analyses, all long-stay and-for feasibility-a random sample (30%) of short-stay survivors were contacted. Primary outcomes were total and post-28-day 5-year mortality. Secondary outcomes comprised handgrip strength (HGF, %pred), 6-minute-walking distance (6MWD, %pred) and SF-36 Physical Function score (PF SF-36). One-to-one propensity-score matching of short-stay and long-stay patients was performed for nutritional strategy, demographics, comorbidities, illness severity and admission diagnosis. Multivariable regression analyses were performed to explore ICU factors possibly explaining any post-ICU observed outcome differences. RESULTS: After matching, total and post-28-day 5-year mortality were higher for long-stayers (48.2% (95%CI: 43.9% to 52.6%) and 40.8% (95%CI: 36.4% to 45.1%)) versus short-stayers (36.2% (95%CI: 32.4% to 40.0%) and 29.7% (95%CI: 26.0% to 33.5%), p<0.001). ICU risk factors comprised hypoglycaemia, use of corticosteroids, neuromuscular blocking agents, benzodiazepines, mechanical ventilation, new dialysis and the occurrence of new infection, whereas clonidine could be protective. Among 276 long-stay and 398 short-stay 5-year survivors, HGF, 6MWD and PF SF-36 were significantly lower in long-stayers (matched subset HGF: 83% (95%CI: 60% to 100%) versus 87% (95%CI: 73% to 103%), p=0.020; 6MWD: 85% (95%CI: 69% to 101%) versus 94% (95%CI: 76% to 105%), p=0.005; PF SF-36: 65 (95%CI: 35 to 90) versus 75 (95%CI: 55 to 90), p=0.002). CONCLUSION: Longer duration of intensive care is associated with excess 5-year mortality and morbidity, partially explained by potentially modifiable ICU factors. TRAIL REGISTRATION NUMBER: NCT00512122.


Assuntos
Estado Terminal/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Força da Mão , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Fatores de Tempo , Teste de Caminhada , Caminhada
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