Value of hemophagocytosis in the diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients.

BACKGROUND: Ferritin is an established biomarker in the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH), which is diagnosed by the HLH-2004 criteria. Among these criteria, detection of hemophagocytosis through invasive procedures may delay early life saving treatment. Our aim was to investigate the value of hemophagocytosis in diagnosing HLH in critically ill patients. METHODS: In this secondary analysis of a retrospective observational study, we included all patients aged ≥18 years and admitted to any adult ICU at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, who had hyperferritinemia (≥500 µg/L) and underwent bone marrow biopsy during their ICU course. RESULTS: Two hundred fifty-two patients were included, of whom 31 (12.3%) showed hemophagocytosis. In multivariable logistic regression analysis, maximum ferritin was independently associated with hemophagocytosis. By removing hemophagocytosis from HLH-2004 criteria and HScore, prediction accuracy for HLH diagnosis was only marginally decreased compared to the original scores. CONCLUSIONS: Our results strengthen the diagnostic value of ferritin and underline the importance of considering HLH diagnosis in patients with high ferritin but only four fulfilled HLH-2004 criteria, when hemophagocytosis was not assessed or not detectable. Proof of hemophagocytosis is not required for a reliable HLH diagnosis.

Preoperative hypoalbuminaemia in liver surgery: an observational study at a university medical centre.

OBJECTIVES: Preoperative hypoalbuminaemia is associated with adverse outcome, including increased postoperative mortality in cardiovascular surgery, neurosurgery, trauma and orthopaedic surgery. However, much less is known about the association between preoperative serum albumin and clinical outcomes after liver surgery. In this study, we sought to determine whether hypoalbuminaemia before partial hepatectomy is associated with a worse postoperative outcome. DESIGN: Observational study. SETTING: University Medical Centre in Germany. PARTICIPANTS: We analysed 154 patients enrolled in the perioperative PHYsostigmine prophylaxis for liver resection patients at risk for DELIrium and postOperative cognitive dysfunction (PHYDELIO) trial with a preoperative serum albumin assessment. Hypoalbuminaemia was defined as serum albumin <35 g/L. Subgroups classified as hypoalbuminaemia and non-hypoalbuminaemia consisted of 32 (20.8%) and 122 (79.2%) patients, respectively. OUTCOME MEASURES: The outcome parameters of interest were postoperative complications according to Clavien (moderate: I, II; major: ≥III), length of intensive care unit (ICU) stay, length of hospital stay and survival rates 1 year after surgery. RESULTS: Preoperative hypoalbuminaemia was associated with the occurrence of major postoperative complications (OR 3.051 (95% CI 1.197 to 7.775); p=0.019) after adjusting for age, sex, randomisation, American Society of Anesthesiologists physical status, preoperative diagnosis and Child-Pugh class. Both ICU and hospital lengths of stay were significantly prolonged in patients with preoperative hypoalbuminaemia (OR 2.573 (95% CI 1.015 to 6.524); p=0.047 and OR 1.296 (95% CI 0.254 to 3.009); p=0.012, respectively). One-year survival was comparable between patients with and without hypoalbuminaemia. CONCLUSIONS: We found that low serum albumin before surgery was associated with a worse short-term outcome after partial hepatectomy, which strengthens the prognostic value of serum albumin in the setting of liver surgery. TRIAL REGISTRATION NUMBERS: ISRCTN18978802 and EudraCT 2008-007237-47.

Interleukin 8 in postoperative delirium - Preliminary findings from two studies.

OBJECTIVE: Studies have suggested that inflammation contributes to the pathogenesis of postoperative delirium, but previous results on the proinflammatory cytokine IL-8 in plasma are contradictory. Additionally, a significant fraction of IL-8 is bound to erythrocytes, but the relevance of whole blood IL-8 in delirium has not been studied. In this work, we analyzed the association of postoperative delirium with levels of unbound IL-8 in plasma and levels of IL-8 in whole blood in patients from two studies which were conducted in our department and have not been presented previously. We assessed the prognostic value of whole blood IL-8. METHODS: Plasma/whole blood IL-8 was measured at least once in N â€‹= â€‹504 patients preoperatively, on day one (d1) and/or three months after surgery in the BioCog observational study. Whole blood IL-8 was measured in N â€‹= â€‹64 patients from the PHYDELIO trial preoperatively, on d1 and d7 after surgery. For the determination of whole blood IL-8, EDTA-preserved blood samples underwent lysis by adding Triton-X100 surfactant. Plasma and whole blood IL-8 levels were assessed with two different immunoassay kits. Delirium was appraised systematically for seven postoperative days according to DSM criteria using two comparable protocols consisting of validated screening tools. RESULTS: Delirium occurred in 25% of BioCog and 14% of PHYDELIO patients. In BioCog, IL-8 was elevated on d1 and in delirious patients. A steeper postoperative increase in delirium was confounded by surgery-related factors. A crescendo-decrescendo pattern of whole blood IL-8 levels was observed in non-delirious patients with a peak on d1. This pattern was more distinct in delirious BioCog patients, but inverted in delirious PHYDELIO patients. Preoperative whole blood IL-8>318.4 â€‹pg/mL (reference <150 â€‹pg/mL) had adequate sensitivity (0.79/0.78) and specificity (0.53/0.67) for delirium in both samples. CONCLUSION: Our results contribute to an inflammatory hypothesis of postoperative delirium.

Differential Diagnosis of Hyperferritinemia in Critically Ill Patients.

BACKGROUND: Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. METHODS: In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 µg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. RESULTS: A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. CONCLUSIONS: Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.