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1.
Crit Care ; 24(1): 244, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448380

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients. METHODS: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 µg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy. RESULTS: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 µg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p <  0.001] were significantly associated with in-hospital mortality. CONCLUSIONS: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients. CLINICAL TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

2.
Crit Care Med ; 48(4): 459-465, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32205591

RESUMO

OBJECTIVE: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients. DESIGN: Retrospective observational study. SETTING: Adult surgical, anesthesiologic, and medical ICUs of a university hospital. PATIENTS: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949-0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384-1.665 per log µg/L]; p < 0.001). CONCLUSIONS: This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.

4.
Minerva Anestesiol ; 86(4): 394-403, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32000470

RESUMO

BACKGROUND: Presurgical cognitive impairment (PreCI) is frequently seen in older age, but the influence on postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) remains unclear. The present study sought to determine the association between PreCI, POD and POCD with special focus to different PreCI domains. METHODS: We analyzed 934 patients with complete baseline neurocognitive assessment. PreCI was determined as cognitive performance of at least two standard deviation (SD) below the mean performance of non-surgical controls. POD was assessed according to the Diagnostic and Statistical Manual of Mental Disorders 4 (DSM-4). POCD at three months follow-up was calculated by the reliable change index (RCI). Associations between PreCI and POD or POCD were assessed using multivariable logistic regression models adjusted for age, sex, randomization, ASA status, type of anesthesia, and type of surgery. RESULTS: PreCI was significantly associated with POD [OR 1.936 (95%CI 1.119 to 3.348); P=0.015] and POCD [OR 3.091 (95%CI 1.287 to 7.426); P=0.012]. Patients with coincident PreCI and POD were significantly more likely to develop POCD [OR 6.131 (95%CI 1.476 to 22.364); P=0.007]. Differentiation between no PreCI, amnestic and non-amnestic PreCI revealed a sole influence of amnestic PreCI on POD and POCD. CONCLUSIONS: Patients ≥ 60 years with PreCI were more likely to develop POD and POCD, respectively. The odds for POCD were highest in patients with PreCI whom also suffered from POD. Amnestic rather than non-amnestic PreCI might play a key role in the development of POD and POCD. These results warrant further pathophysiological investigations and demand preventive strategies.

5.
Anesth Analg ; 130(2): 341-351, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30855340

RESUMO

BACKGROUND: Skeletal muscle failure in critical illness (intensive care unit-acquired weakness) is a well-known complication developing early during intensive care unit stay. However, muscle weakness during the perioperative setting has not yet been investigated. METHODS: We performed a subgroup investigation of a prospective observational trial to investigate perioperative muscle weakness. Eighty-nine patients aged 65 years or older were assessed for handgrip strength preoperatively, on the first postoperative day, at intensive care unit discharge, at hospital discharge, and at 3-month follow-up. Functional status was evaluated perioperatively via Barthel index, instrumental activities of daily living, Timed Up and Go test, and functional independence measure. After exclusion of patients with intensive care unit-acquired weakness or intensive care unit stay of ≥72 hours, 59 patients were included into our analyses. Of these, 14 patients had additional pulmonary function tests preoperatively and on postoperative day 1. Blood glucose was measured intraoperatively every 20 minutes. RESULTS: Handgrip strength significantly decreased after surgery on postoperative day 1 by 16.4% (P < .001). Postoperative pulmonary function significantly decreased by 13.1% for vital capacity (P = .022) and 12.6% for forced expiratory volume in 1 second (P = .001) on postoperative day 1. Handgrip strength remained significantly reduced at hospital discharge (P = .016) and at the 3-month follow-up (P = .012). Perioperative glucose levels showed no statistically significant impact on muscle weakness. Instrumental activities of daily living (P < .001) and functional independence measure (P < .001) were decreased at hospital discharge, while instrumental activities of daily living remained decreased at the 3-month follow-up (P = .026) compared to preoperative assessments. CONCLUSIONS: Perioperatively acquired weakness occurred, indicated by a postoperatively decreased handgrip strength, decreased respiratory muscle function, and impaired functional status, which partly remained up to 3 months.

6.
Crit Care Clin ; 36(1): 1-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733671

RESUMO

Sepsis is one of the oldest and most elusive syndromes in medicine that is still incompletely understood. Biomarkers may help to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders. This will help to differentiate between systemic inflammation of infectious and noninfectious origin and aid therapeutic decision making, hence improve the prognosis for patients, guide antimicrobial therapy, and foster the development of novel adjunctive sepsis therapies. To reach this goal requires increased systematic investigation that includes twenty-first century scientific approaches and technologies and appropriate clinical evaluation.


Assuntos
Anti-Infecciosos/história , Anti-Infecciosos/uso terapêutico , Monitoramento Biológico/história , Biomarcadores/sangue , Sepse/diagnóstico , Sepse/tratamento farmacológico , Monitoramento Biológico/métodos , História do Século XX , História do Século XXI , Humanos , Valor Preditivo dos Testes , Sepse/sangue
7.
BMJ Open ; 9(10): e032695, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666276

RESUMO

INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated. METHODS AND ANALYSIS: The HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité - Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine. ETHICS AND DISSEMINATION: The institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité - Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03510650.

8.
Shock ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626037

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the ICU is challenged by the clinical overlap with sepsis. Here, we analyze HLH patients to better understand its clinical presentation, diagnosis and treatment. METHODS: For the purpose of this retrospective observational study, we searched for suspected and diagnosed adult HLH of all patients admitted to at least one adult surgical, anesthesiological or medical ICU between January 2006 and August 2018 at the university hospital Charité - Universitätsmedizin Berlin. All cases were reviewed by two HLH experts, who confirmed or declined the diagnosis. RESULTS: Of 6340 ICU patients with ferritin measurement, 40 suffered from HLH (0.63%). Of these, in-hospital mortality was 60.0% over all cases, which was highest in malignancy-associated HLH (71.4%). Infections were identified as most common triggers (42.5%). A variety of 19 different treatment strategies were applied. Non-survivors showed higher ferritin at diagnosis compared to survivors (p = 0.021), which was also seen in multivariable analyses. A minimum ferritin of 4083 µg/L after diagnosis was most predictive for 30-day mortality (AUC 0.888, 95% CI 0.771-1.000; sensitivity 93.8%, specificity 78.9%). CONCLUSIONS: Mortality in adult HLH patients in the ICU is high, particularly in malignancy-associated HLH. Infections are the most frequent HLH triggers in critically ill patients. At present, there is no standardized treatment for HLH in adult patients available. Assessment of ferritin is valuable for diagnosis, prognosis, and treatment monitoring. TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

9.
Lancet Infect Dis ; 19(12): e422-e436, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630991

RESUMO

Increasing evidence supports a central role of the immune system in sepsis, but the current view of how sepsis affects immunity, and vice versa, is still rudimentary. The European Group on Immunology of Sepsis has identified major gaps that should be addressed with high priority, such as understanding how immunological alterations predispose to sepsis, key aspects of the immunopathological events during sepsis, and the long-term consequences of sepsis on patient's immunity. We discuss major unmet topics in those three categories, including the role of key immune cells, the cause of lymphopenia, organ-specific immunology, the dynamics of sepsis-associated immunological alterations, the role of the microbiome, the standardisation of immunological tests, the development of better animal models, and the opportunities offered by immunotherapy. Addressing these gaps should help us to better understand sepsis physiopathology, offering translational opportunities to improve its prevention, diagnosis, and care.

10.
Minerva Anestesiol ; 85(11): 1201-1210, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486622

RESUMO

BACKGROUND: Hyperglycemia frequently occurs during major surgery and is associated with adverse postoperative outcomes. This study aimed to investigate the influence of intraoperative hyperglycemia on incidences of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). METHODS: Eighty-seven patients aged ≥65 years undergoing elective surgery were included in this prospective observational subproject of the BioCog study. Blood glucose (BG) levels were measured every 20 minutes intraoperatively. Hyperglycemia was defined as BG levels ≥150 mg·dL-1. Patients were assessed for POD twice daily until postoperative day 7. The occurrence of POCD was determined three months after surgery. Multivariable logistic regression was used to identify associations between hyperglycemia and POD as well as POCD. Secondary endpoints comprised duration of hyperglycemia, maximum glucose level (Glucosemax) and differences between diabetic and non-diabetic patients. RESULTS: POD occurred in 41 (47.1%), POCD in five (15.2%) patients. In two separate multivariable logistic regression models, hyperglycemia was significantly associated with POD (OR 3.86 [CI 95% 1.13, 39.49], P=0.044) but not POCD (3.59 [NaN, NaN], P=0.157). Relative duration of hyperglycemia was higher in POD patients compared to patients without POD (20 [0; 71] % versus 0 [0; 55] %, P=0.075), whereas the maximum glucose levels during surgery were similar between the two groups. Considering only non-diabetic patients, relative duration of hyperglycemia (P=0.003) and Glucosemax (P=0.015) were significantly higher in patients with POD. CONCLUSIONS: Intraoperative hyperglycemia was independently associated with POD but not POCD. Relative duration of hyperglycemia appeared thereby to also play a role. Especially hyperglycemic non-diabetic patients might be at high risk for POD.

11.
Anaesthesist ; 68(9): 626-632, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31396675

RESUMO

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome or macrophage activation syndrome within a pre-existing rheumatological disease, remains undiagnosed in over 70% of all cases in intensive care units (ICU) due to the sepsis-like clinical presentation. This report describes the case of a 30-year-old previously healthy male patient who was admitted to the normal infectiology ward of the Charité - Universitätsmedizin Berlin with unclear fever after a 3­month journey around Asian and South America. The patient was transferred to the ICU after 3 days because of respiratory failure. Due to the immediate diagnostics of HLH and initiation of specific immunosuppressive treatment with dexamethasone, immunoglobulins and anakinra, the patient completely recovered and could finally be discharged after a 2­week stay in hospital. Furthermore, the current diagnostic and therapeutic options are discussed. Ferritin is a decisive diagnostic marker that should be determined in every patient with unclear organ failure.

12.
Acta Anaesthesiol Scand ; 63(10): 1282-1289, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31283835

RESUMO

BACKGROUND: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. METHODS: In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery. Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. RESULTS: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269]. CONCLUSIONS: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD. TRIAL REGISTRATION: This study was registered with ISRCTN Register 36437985 on 02 March 2009.

13.
Int J Med Sci ; 16(5): 665-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217734

RESUMO

BACKGROUNDː Dysglycemia is associated with adverse outcome including increased morbidity and mortality in surgical patients. Acute insulin resistance due to the surgical stress response is seen as a major cause of so-called stress hyperglycemia. However, understanding of factors determining blood glucose (BG) during surgery is limited. Therefore, we investigated risk factors contributing to intraoperative dysglycemia. METHODSː In this subgroup investigation of the BIOCOG study, we analyzed 87 patients of ≥ 65 years with tight intraoperative BG measurement every 20 min during elective surgery. Dysglycemia was defined as at least one intraoperative BG measurement outside the recommended target range of 80-150 mg/dL. Additionally, all postoperative BG measurements in the ICU were obtained. Multivariable logistic regression analysis adjusted for age, sex, American Society of Anesthesiologists (ASA) status, diabetes, type and duration of surgery, minimum Hemoglobin (Hb) and mean intraoperative norepinephrine use was performed to identify risk factors of intraoperative dysglycemia. RESULTSː 46 (52.9%) out of 87 patients developed intraoperative dysglycemia. 31.8% of all intraoperative BG measurements were detected outside the target range. Diabetes [OR 9.263 (95% CI 2.492, 34.433); p=0.001] and duration of surgery [OR 1.005 (1.000, 1.010); p=0.036] were independently associated with the development of intraoperative dysglycemia. Patients who experienced intraoperative dysglycemia had significantly elevated postoperative mean (p<0.001) and maximum BG levels (p=0.001). Length of ICU (p=0.007) as well as hospital stay (p=0.012) were longer in patients with dysglycemia. CONCLUSIONSː Diabetes and duration of surgery were confirmed as independent risk factors for intraoperative dysglycemia, which was associated with adverse outcome. These patients, therefore, might require intensified glycemic control. Increased awareness and management of intraoperative dysglycemia is warranted.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus/cirurgia , Hiperglicemia/epidemiologia , Complicações Intraoperatórias/epidemiologia , Idoso , Glicemia/metabolismo , Complicações do Diabetes/patologia , Complicações do Diabetes/cirurgia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Feminino , Humanos , Hiperglicemia/etiologia , Hiperglicemia/patologia , Hiperglicemia/cirurgia , Insulina/metabolismo , Resistência à Insulina/genética , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/patologia , Complicações Intraoperatórias/cirurgia , Masculino , Fatores de Risco
14.
PLoS One ; 14(6): e0218411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31199858

RESUMO

BACKGROUND: Cerebral microbleeds (CMB) occur in the context of cerebral small vessel disease. Other brain MRI markers of cerebral small vessel disease are associated with the occurrence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), but for CMB this is unknown. We aimed to study the association between CMB and the occurrence of POD and POCD in older individuals. METHODS: The current study consists of 65 patients (72±5 years) from the BIOCOG study, which is a prospective, observational study of patients who underwent an elective surgery of at least 60 minutes. Patients in the current study received a preoperative cerebral MRI scan including a 3D susceptibility-weighted imaging sequence to detect CMB. The occurrence of POD was screened for twice a day until postoperative day 7 by using the DSM-5, NuDesc, CAM, and CAM-ICU. The occurrence of POCD was determined by the reliable change index model at 7 days after surgery or discharge, respectively, and 3 months after surgery. Statistical analyses consisted of logistic regression adjusted for age and gender. RESULTS: A total of 39 CMB were detected in 17 patients (26%) prior to surgery. POD occurred in 14 out of 65 patients (22%). POCD at 7 days after surgery occurred in 11 out of 54 patients (20%) and in 3 out of 40 patients at the 3 month follow-up (8%). Preoperative CMB were not associated with the occurrence of POD (OR (95%-CI): 0.28 (0.05, 1.57); p = 0.147) or POCD at 7 days after surgery (0.76 (0.16, 3.54); p = 0.727) or at 3 months follow-up (0.61 (0.03, 11.64); p = 0.740). CONCLUSION: We did not find an association between preoperative CMB and the occurrence of POD or POCD. TRIAL REGISTRATION: clinicaltrials.gov (NCT02265263) on 23 September 2014.


Assuntos
Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Delírio/diagnóstico , Delírio/etiologia , /etiologia , Fatores Etários , Idoso , Biomarcadores , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Razão de Chances
15.
Blood ; 133(23): 2465-2477, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-30992265

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Adulto , Feminino , Humanos , Masculino
16.
J Neuroimaging ; 29(2): 260-267, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30468268

RESUMO

BACKGROUND AND PURPOSE: In hyperglycemic patients, who succumbed to septic shock, an increased rate of apoptosis of microglial cells and damaged neurons of the hippocampus were found. However, the influence of perioperative glucose levels on hippocampal brain structures has not yet been investigated. METHODS: As part of the ongoing BIOCOG project, a subgroup of N = 65 elderly nondemented patients were analyzed who underwent elective surgery of ≥60 minutes. In these patients, at least one intraoperative blood glucose (BG) measurement was available from the medical charts. Intraoperative glucose maximum was determined in each patient. Preoperatively and at 3 months follow-up, structural neuroimaging was performed with T1-weighted magnetization prepared rapid gradient-echo sequence (MP-Rage) and a dedicated high-resolution hippocampus magnetic resonance imaging (MRI). The MRI scans were analyzed to assess pre- or postoperative volume changes of the hippocampus as a whole and hippocampal subfields. We also assessed changes of frontal lobe volume and cortical thickness. RESULTS: Overall, 173 intraoperative BG levels were obtained in 65 patients (median 2 per patient). A total of 18 patients showed intraoperative hyperglycemia (glucose maximum ≥150 mg/dL). Controlling for age and diabetes status, no significant impact of intraoperative hyperglycemia was found on the pre-post volume change of the hippocampus as a whole, hippocampal subfields, frontal lobe, and frontal cortical thickness. CONCLUSIONS: This study found no effect of intraoperative hyperglycemia on postoperative brain structures and volumes including volumes of hippocampus and hippocampal subfields, frontal lobe, and frontal cortical thickness. Further studies investigating the impact of intraoperatively elevated glucose levels should consider a tighter or even continuous glycemic measurement and the determination of central microglial activation.

17.
Dement Geriatr Cogn Disord ; 46(3-4): 193-206, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30326480

RESUMO

BACKGROUND/AIMS: Older people undergoing surgery are at risk of developing postoperative cognitive dysfunction (POCD), but little is known of risk factors predisposing patients to POCD. Our objective was to estimate the risk of POCD associated with exposure to preoperative diabetes, hypertension, and obesity. METHODS: Original data from 3 randomised controlled trials (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis on diabetes, hypertension, baseline blood pressure, obesity (BMI ≥30 kg/m2), and BMI as risk factors for POCD in multiple logistic regression models. Risk estimates were pooled across the 3 studies. RESULTS: Analyses totalled 1,034 patients. POCD occurred in 5.2% of patients in DECS, in 9.4% in SuDoCo, and in 32.1% of patients in OCTOPUS. After adjustment for age, sex, surgery type, randomisation, obesity, and hypertension, diabetes was associated with a 1.84-fold increased risk of POCD (OR 1.84; 95% CI 1.14, 2.97; p = 0.01). Obesity, BMI, hypertension, and baseline blood pressure were each not associated with POCD in fully adjusted models (all p > 0.05). CONCLUSION: Diabetes, but not obesity or hypertension, is associated with increased POCD risk. Consideration of diabetes status may be helpful for risk assessment of surgical patients.


Assuntos
Disfunção Cognitiva , Delírio , Diabetes Mellitus , Hipertensão , Obesidade , Complicações Pós-Operatórias , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Delírio/diagnóstico , Delírio/etiologia , Delírio/fisiopatologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/psicologia , Medição de Risco/métodos , Fatores de Risco
18.
Clin Epidemiol ; 10: 853-862, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30100759

RESUMO

Background: Age-related cognitive impairment is rising in prevalence but is not yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate the role of obesity, diabetes and hypertension as candidate risk factors. Methods: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis of cross-sectional associations of diabetes, hypertension, blood pressure, obesity (body mass index [BMI] ≥30 kg/m2) and BMI with presence of cognitive impairment in log-binomial regression analyses. Cognitive impairment was defined as scoring more than 2 standard deviations below controls on at least one of 5-11 cognitive tests. Underweight participants (BMI<18.5 kg/m2) were excluded. Results were pooled across studies in fixed-effects inverse variance models. Results: Analyses totaled 1545 participants with a mean age of 61 years (OCTOPUS) to 70 years (SuDoCo). Cognitive impairment was found in 29.0% of participants in DECS, 8.2% in SuDoCo and 45.6% in OCTOPUS. In pooled analyses, after adjustment for age, sex, diabetes and hypertension, obesity was associated with a 1.29-fold increased prevalence of cognitive impairment (risk ratio [RR] 1.29; 95% CI 0.98, 1.72). Each 1 kg/m2 increment in BMI was associated with 3% increased prevalence (RR 1.03; 95% CI 1.00, 1.06). None of the remaining risk factors were associated with impairment. Conclusion: Our results show that older people who are obese have higher prevalence of cognitive impairment compared with normal weight and overweight individuals, and independently of co-morbid hypertension or diabetes. Prospective studies are needed to investigate the temporal relationship of the association.

19.
Shock ; 50(2): 149-155, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30010630

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis in adults (aHLH) is a rare life-threatening hyperinflammatory syndrome caused by excessive activation of macrophages and CD8+ T-cells. Due to the clinical overlap with severe sepsis, aHLH often remains undiagnosed resulting in poor outcome. Here, we present a retrospective study of incidence, clinical findings, and the outcome of aHLH in intensive care units (ICUs). METHODS: This retrospective analysis was performed at the university hospital Charité - Universitätsmedizin Berlin. We gathered data from 556 out of 46,532 patients admitted to our anesthesiological ICUs between 2006 and 2013, who had at least one plasma ferritin measurement during ICU treatment, and were at least 18 years old. Of these, 244 patients with ferritin at least 500 µg/L and available datasets of at least 4 HLH-2004 criteria were included. HLH-2004 diagnostic criteria and the recently published HScore were used. An aHLH expert team retrospectively reviewed the potential aHLH cases. RESULTS: Seventy-one of the included 244 patients died; 9 out of the 244 patients were retrospectively classified as aHLH of whom 4 patients had died (44.4%). Two of the 9 aHLH patients had been correctly diagnosed and had received specific aHLH treatment. Thus, 7 out of 9 patients (77.8%) remained undetected. ICU patients with at least 1 captured ferritin value and hyperferritinemia showed an aHLH rate of 3.7%, which rises up to 5.6% when only deceased patients are considered. Mortality in this selected cohort is 44.4%. CONCLUSIONS: Overall, 7 out of 9 patients (77.8%) suffering from aHLH remained undiagnosed. Awareness of this life-threatening syndrome, especially in ICUs, should be raised. The inclusion of ferritin into the admission lab panel for ICU is warranted.Clinical trial registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016. As this is a retrospective study, trial registration was after final data collection date.


Assuntos
Cuidados Críticos , Bases de Dados Factuais , Ferritinas/sangue , Unidades de Terapia Intensiva , Linfo-Histiocitose Hemofagocítica , Adulto , Idoso , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Int J Med Sci ; 15(1): 1-9, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29333081

RESUMO

Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed. Innate and acquired immune cells, the expression of human leukocyte antigen-D related on monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-α and IL-10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after surgery (pod5). Recovery of immune cells was defined by a significant decrease respectively increase after a significant postoperative alteration. Statistical analyses were performed using nonparametric statistical procedures. Results: Postoperative alterations of innate immune cells recovered on pod2 (eosinophils), pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-α and IL-10 secretion), whereas alterations of acquired immune cells (lymphocytes, T cells, T helper cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T cells showed an impaired production of the T helper (Th) 1 cytokine IFN-γ upon Con A stimulation on pod1, while Th2 specific cytokine release did not change until pod5.Conclusions: Innate immunity recovered earlier than acquired immunity during severe postoperative immunosuppression. Furthermore, we found a more anti- than pro-inflammatory T cell function on the first day after surgery, while T cell counts decreased.


Assuntos
Imunidade Adaptativa/fisiologia , Tolerância Imunológica/fisiologia , Imunidade Inata/fisiologia , Linfócitos/imunologia , Complicações Pós-Operatórias/imunologia , Idoso , Citocinas/imunologia , Citocinas/metabolismo , Esofagectomia/efeitos adversos , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Pancreatectomia/efeitos adversos , Complicações Pós-Operatórias/sangue , Estudos Retrospectivos , Fatores de Tempo
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