Introduction: suPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR), which is expressed in various immunologically active cells. High suPAR serum concentrations are suggested to reflect the activation of the immune system in circumstances of inflammation and infection, and have been associated with increased mortality in different populations of non-intensive care patients. In this study we sequentially analyzed suPAR serum concentrations within the first week of intensive care in a large cohort of well characterized intensive care unit (ICU) patients, in order to investigate potential regulatory mechanisms and evaluate the prognostic significance in critically ill patients. Methods: A total of 273 patients (197 with sepsis, 76 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU), on Day 3 and Day 7, and compared to 43 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately one year. Results: Upon admission to the ICU suPAR serum concentrations were elevated in critically ill patients as compared with healthy controls. In sepsis patients suPAR levels were higher than in non-sepsis patients (with or without systemic inflammatory response syndrome (SIRS)). During the first week after admission to the ICU serum suPAR concentrations remained stably elevated. suPAR serum concentrations measured upon admission were closely and independently correlated to various laboratory parameters, specifically biomarkers of inflammation (tumor necrosis factor (TNF), C-reactive protein (CRP)), hepatic and renal dysfunction. High suPAR levels at admission and at Day 3 were a strong independent predictor for both ICU and long-term mortality in critically ill patients. Conclusions: In sepsis and non-sepsis patients suPAR serum concentrations are increased upon admission to the ICU, likely reflecting the activation state of the immune system, and remain stably elevated in the initial course of treatment. Low suPAR levels are a positive predictor of ICU- and overall survival in critically ill patients, including sepsis and non-sepsis patients. Aside from its value as a promising new prognostic biomarker, both experimental and clinical studies are required in order to understand the specific effects and regulatory mechanisms of suPAR in SIRS and sepsis, and may reveal new therapeutic options.

Introduction: Blood glucose levels and insulin resistance in critically ill patients on admission to intensive care units (ICUs) have been identified as factors influencing mortality. The pathogenesis of insulin resistance (IR) in critically ill patients is complex and not fully understood. Resistin is a hormone mainly derived from macrophages in humans and from adipose tissue in rodents, which regulates glucose metabolism and insulin sensitivity. In non-critically ill patients, resistin was found to be related to impaired glucose tolerance, insulin resistance, metabolic syndrome, obesity and type 2 diabetes. Therefore, resistin might represent a link between inflammation, acute phase response and insulin resistance in critically ill patients. We aimed to examine the correlation of serum resistin concentrations to parameters of inflammation, organ function, metabolism, disease severity and survival in critically ill patients. Methods: On admission to the Medical ICU, 170 patients (122 with sepsis, 48 without sepsis) were studied prospectively and compared with 60 healthy non-diabetic controls. Clinical data, various laboratory parameters, metabolic and endocrine functions as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately three years. Results: Resistin serum concentrations were significantly elevated in all critical care patients compared with healthy controls, and significantly higher in sepsis than in non-sepsis patients. Serum resistin concentrations were not associated with pre-existing type 2 diabetes or obesity. For all critically ill patients, a correlation to the homeostasis model assessment index of insulin resistance (HOMA-IR) was shown. Serum resistin concentrations were closely correlated to inflammatory parameters such as C-reactive protein, leukocytes, procalcitonin, and cytokines such as IL6 and TNF-α, as well as associated with renal failure and liver synthesis capacity. High resistin levels (> 10 ng/ml) were associated with an unfavourable outcome in non-sepsis patients on ICU and the overall survival. Conclusions: Serum resistin concentrations are elevated in acute inflammation due to sepsis or systemic inflammatory response syndrome (SIRS). The close correlation with other acute phase proteins suggests a predominant, clinically relevant resistin release from macrophages in ICU patients. Moreover, resistin could potentially serve as a prognostic biomarker in non-sepsis critically ill patients.

Lymphopenia and functional defects in lymphocytes may impact the prognosis in patients with critical illness or sepsis. Therefore, we prospectively analyzed peripheral blood leukocytes from 63 healthy volunteers, 50 non-critically ill standard care (SC) patients with infections, and 105 intensive care unit (ICU) patients (52 with sepsis, 53 without sepsis) using flow cytometry. Compared to healthy volunteers, SC and ICU patients showed significant leukocytosis, especially in sepsis, while lymphocyte numbers were significantly decreased. All major lymphocyte populations (B, T, and natural killer (NK) cells) decreased in ICU patients. However, we observed a relative reduction of T cells, alongside decreased CD8+ T cells, in critically ill patients, independent of sepsis. High absolute T cell counts (>0.36/nL) at ICU admission were associated with a significantly reduced mortality, independent of patient’s age. Moreover, patients that survived ICU treatment showed dynamic changes within 48 h towards restoration of lymphopenia and T cell depletion, while non-surviving patients failed to restore lymphocyte counts. In conclusion, the flow-cytometric analysis of peripheral blood revealed striking changes in circulating lymphocyte subsets in critically ill patients, independent of sepsis. Lymphopenia and T cell depletion at ICU admission were associated with increased mortality, supporting their relevance as predictive biomarkers and potential therapeutic targets in intensive care medicine.

Introduction: Hepatic dysfunction is a common finding in critically ill patients on the ICU and directly influences survival. Liver stiffness can be measured by the novel method of transient elastography (fibroscan) and is closely associated with hepatic fibrosis in patients with chronic liver disease, but also is increased in patients with acute hepatitis, acute liver failure and cholestasis. We investigated liver stiffness as a potentially useful tool for early detection of patients with hepatic deterioration and risk stratification with respect to short- and long-term mortality.Methods: We prospectively evaluated 108 consecutive critically ill patients at our medical intensive care unit (ICU) with subsequent longitudinal liver stiffness measurements (admission, Day 3, Day 7 and weekly thereafter) during the course of ICU treatment. Outcome was followed after discharge (median observation time 237 days).Results: Liver stiffness could be reliably measured in 71% of ICU patients at admission (65% at Day 3, 63% at Day 7). Critically ill patients (n= 108) had significantly increased liver stiffness compared to sex- and age-matched standard care patients (n= 25). ICU patients with decompensated cirrhosis showed highest liver stiffness, whereas other critical diseases (for example, sepsis) and comorbidities (for example, diabetes, obesity) did not impact stiffness values. At admission to the ICU, liver stiffness is closely related to hepatic damage (liver synthesis, cholestasis, fibrosis markers). During the course of ICU treatment, fluid overload (renal failure, volume therapy) and increased central venous pressure (mechanical ventilation, heart failure) were major factors determining liver stiffness. Liver stiffness values > 18 kilopascal (kPa) at ICU admission were associated with increased ICU and long-term mortality, even in non-cirrhotic patients.Conclusions: Considering that liver stiffness cannot be validly measured in about 30% of ICU patients, transient elastography performed at ICU admission might be a useful tool to early identify liver dysfunction and predict mortality in critically ill patients at a medical ICU.

Introduction: Ghrelin has been recently identified as a mediator of various beneficial effects in animal models of sepsis. At present, no data are available concerning specific properties of ghrelin in critically ill patients from large cohorts. In order to identify possible pathogenic functions of ghrelin in critically ill patients and human sepsis from a clinical point of view, we aimed at analyzing ghrelin serum concentrations in a large cohort of well characterized patients with critical illness. Methods: A total of 170 critically ill patients (122 with sepsis, 48 without sepsis) were studied prospectively on admission to the Medical intensive care unit (ICU) and compared to 60 healthy controls. Careful assessment of clinical data, various laboratory parameters, metabolic and endocrine functions as well as investigational inflammatory cytokine profiles have been performed, and patients were followed for approximately three years. Results: Ghrelin serum concentrations are elevated in critically ill patients as compared to healthy controls, but do not differ between sepsis and non-sepsis patients. The underlying etiologies of critical diseases are not associated with ghrelin serum levels. Neither pre-existing diabetes mellitus nor body mass index is correlated to serum ghrelin concentrations. Ghrelin is not correlated to markers of inflammation or hepatic function in critically ill patients. In the subgroup of non-sepsis patients, ghrelin correlates inversely with renal function and markers of carbohydrate metabolism. High ghrelin levels are an indicator for a favourable prognosis concerning mortality at the ICU in sepsis patients. Furthermore, ghrelin is significantly associated with the necessity of ventilation in critically ill patients. Conclusions: Ghrelin serum concentrations are elevated in all circumstances of critical disease, including sepsis and non-sepsis patients. High ghrelin levels are a positive predictor of ICU-survival in sepsis patients, matching previous results from animal models. Future experimental and clinical studies are needed to evaluate ghrelin as a novel prognostic tool in ICU patients and its potential therapeutic use in sepsis.

Acute pancreatitis (AP) represents one of the most common reasons for hospital admission and intensive care treatment in internal medicine. The incidence of AP is increasing, posing significant financial burden on healthcare systems due to the necessity for frequent medical interventions. Severe acute pancreatitis (SAP) is a potentially life-threatening condition with substantial morbidity and mortality. The management of SAP requires prolonged hospitalization and the expertise of a multidisciplinary team, comprising emergency physicians, intensivists, internists, gastroenterologists, visceral surgeons, and experts in nutrition, infectious disease, endoscopy, as well as diagnostic and interventional radiology. Effective management and beneficial patient outcomes depend on continuous interdisciplinary collaboration. This review synthesizes recent evidence guiding the practical management of SAP, with a particular focus on emergency and intensive care settings. Both established as well as new diagnostic and therapeutic paradigms are highlighted, including workup, risk stratification, fluid management, analgesia, nutrition, organ support, imaging modalities and their timing, along with anti-infective strategies. Furthermore, the review explores interventions for local and vascular complications of SAP, with particular attention to the indications, timing and selection between endoscopic (both endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS)), percutaneous and surgical approaches. Similarly, the management of biliary AP due to obstructive gallstones, including the imaging, timing of ERCP and cholecystectomy, are discussed. By integrating new evidence with relevant guidance for everyday clinical practice, this review aims to enhance the interdisciplinary approach essential for improving outcomes in SAP management.