Soluble Semaphorin 4D Serum Concentrations Are Elevated in Critically Ill Patients with Liver Cirrhosis and Correlate with Aminotransferases.

Semaphorin 4D (Sema4D), also known as CD100, is a multifunctional transmembrane protein with immunoregulatory functions. Upon the activation of immune cells, soluble Semaphorin 4D (sSema4D) is proteolytically cleaved from the membrane by metalloproteinases. sSema4D levels are elevated in various (auto-)inflammatory diseases. Our aim was to investigate sSema4D levels in association with sepsis and critical illnesses and to evaluate sSema4D's potential as a prognostic biomarker. We measured sSema4D levels in 192 patients upon admission to our medical intensive care unit. We found similar levels of sSema4D in 125 patients with sepsis compared to 67 non-septic patients. sSema4D levels correlated with leukocytes but not with other markers of systemic inflammation such as C-reactive protein or procalcitonin. Most interestingly, in a subgroup of patients suffering from pre-existing liver cirrhosis, we observed significantly higher levels of sSema4D. Consistently, sSema4D was also positively correlated with markers of hepatic and cholestatic injury. Our study suggests that sSema4D is not regulated in sepsis compared to other causes of critical illness. However, sSema4D seems to be associated with hepatic injury and inflammation.

Secreted Frizzled Related Protein 5 (SFRP5) Serum Levels Are Decreased in Critical Illness and Sepsis and Are Associated with Short-Term Mortality.

Sepsis is a major health burden with insufficiently understood mechanisms of inflammation and immune paralysis, leading to a life-threatening critical illness. The secreted frizzled related protein 5 (SFRP5) acts as an anti-inflammatory adipokine by antagonizing the Wnt5a pathway. The aim of this study was to elucidate the role of SFRP5 in critical illness and sepsis and to determine its value as a prognostic biomarker for mortality. We analyzed SFRP5 serum concentrations of 223 critically ill patients at admission to a medical intensive care unit (ICU) and compared those to 24 healthy individuals. SFRP5 serum concentrations were significantly decreased in critical illness as compared to healthy controls (24.66 vs. 100 ng/mL, p = 0.029). Even lower serum concentrations were found in septic as compared to nonseptic critically ill patients (19.21 vs. 32.83 ng/mL, p = 0.031). SFRP5 concentrations correlated with liver disease, age, anti-inflammation, and metabolic parameters. Furthermore, patients with sepsis recovered levels of SFRP5 in the first week of ICU treatment. SFRP5 levels at admission predicted short-term mortality in critically ill but not in septic patients. This study points to the role of the anti-inflammatory mediator SFRP5 not only in sepsis but also in nonseptic critically ill patients and associates high levels of SFRP5 to worse outcomes, predominantly in nonseptic critically ill patients.

Elevated Midkine Serum Levels Are Associated with Long-Term Survival in Critically Ill Patients.

Midkine (Mdk) is a multifunctional protein involved in inflammatory processes. Hence, circulating Mdk is increased in sepsis and has been previously suggested as a potential biomarker in these patients. The aim of this study was to elucidate the role of Mdk serum concentrations in critical illness and sepsis and to verify its value as a prognostic biomarker. Thus, we analyzed the Mdk serum concentrations of 192 critically ill patients on admission to the medical intensive care unit (ICU). While the serum levels of Mdk at admission were similar in septic and nonseptic critical illness (362 vs. 337 ng/L, p = 0.727), we found several interesting correlations of Mdk to laboratory and clinical markers associated with ischemia or hypoxia, e.g., to renal failure and hepatic injury. Mdk serum concentrations at admission did not differ between various causes of sepsis or other critical illness. Most noticeable, we observed upregulated Mdk serum concentrations at admission in patients surviving in the long-term, which was only seen in nonseptic critical illness but not in sepsis. Our study suggests a relevant role of Mdk in critically ill patients in general and highlights the possible protective features of Mdk in critical illness.

Decreased Bone Mineral Density Is a Predictor of Poor Survival in Critically Ill Patients.

Alterations in bone mineral density (BMD) have been suggested as independent predictors of survival for several diseases. However, little is known about the role of BMD in the context of critical illness and intensive care medicine. We therefore evaluated the prognostic role of BMD in critically ill patients upon admission to an intensive care unit (ICU). Routine computed tomography (CT) scans of 153 patients were used to assess BMD in the first lumbar vertebra. Results were correlated with clinical data and outcomes. While median BMD was comparable between patients with and without sepsis, BMD was lower in patients with pre-existing arterial hypertension or chronic obstructive pulmonary disease. A low BMD upon ICU admission was significantly associated with impaired short-term ICU survival. Moreover, patients with baseline BMD < 122 HU had significantly impaired overall survival. The prognostic relevance of low BMD was confirmed in uni- and multivariate Cox-regression analyses including several clinicopathological parameters. In the present study, we describe a previously unrecognised association of individual BMD with short- and long-term outcomes in critically ill patients. Due to its easy accessibility in routine CT, BMD provides a novel prognostic tool to guide decision making in critically ill patients.

Hemosuccus Pancreaticus and Obstructive Jaundice: Two Rare Complications of Chronic Pancreatitis Treated by Arterial Embolization.

The formation of a peripancreatic pseudoaneurysm is a rare and serious complication of chronic pancreatitis. In this report, we present the case of a 56-year-old male with a history of alcohol-related chronic pancreatitis resulting in both hemosuccus pancreaticus and obstructive jaundice due to a pseudoaneurysm of the gastroduodenal artery that was treated successfully by angiographic coiling.

Skeletal Muscle Composition Predicts Outcome in Critically Ill Patients.

Parameters of patients' body composition have been suggested as prognostic markers in several clinical conditions including cancer and liver transplantation, but only limited data on its value in critical illness exist to date. In this study, we aimed at evaluating a potential prognostic value of the skeletal muscle mass and skeletal muscle myosteatosis of critically ill patients at admission to the ICU. DESIGN: Exploratory observational cohort study. SETTING: An urban, academic medical institution. PATIENTS: One-hundred fifty-five patients treated for critical illness on a medical ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used routine CT scans to assess the patients' individual body composition. The skeletal muscle index as a surrogate for sarcopenia was defined as the total skeletal muscle area at the level of the third lumbar vertebra on axial CT scan, normalized for the patient's height. Myosteatosis was evaluated by assessing the mean skeletal muscle attenuation measured in Hounsfield unit at the same sectional plane. The skeletal muscle index and mean skeletal muscle attenuation at admission to the ICU were significantly higher in patients with long-term survival (180-day or 1-year mortality), while both parameters were comparable between short-term survivors and nonsurvivors (ICU mortality or 30-d mortality). Patients with a skeletal muscle index or mean skeletal muscle attenuation below our established ideal cutoff values (74.95 mm2/cm and 29 Hounsfield unit) showed a significantly reduced overall survival. These findings were confirmed in univariate and multivariate Cox regression analyses. Furthermore, myosteatosis significantly correlated with the time of mechanical ventilation, the duration of hospital stay, and the presence of sepsis. CONCLUSIONS: Our data suggest that sarcopenia and myosteatosis represent important prognostic factors in critically ill patients that can be easily obtained from routine CT scans. Both parameters at admission to the ICU yield important information on the patients' long-term outcome and might be used for early clinical decision-making in these patients.

[Nutrition Support Therapy in Critically Ill Patients]. / Ernährungstherapie des Intensivpatienten.

Nutritional therapy is an elemental component of intensive care treatment. Therapeutic goals are the enteral or parenteral provision of calories, protein, electrolytes, vitamins and trace elements. Pathophysiologically, metabolism in critical illness is characterized by a catabolic stress status. This results from an underlying systemic inflammatory response and is associated with increased rate of infections, multiple organ failure and unfavourable outcome. In this article, the principles and strategies of nutrition support therapy in critically ill patients are presented, based on current guidelines.

[Current Developments in Nutritional Therapy of Intensive Care Patients]. / Aktuelle Entwicklungen in der Ernährungstherapie von Intensivpatienten.

The goals of nutritional therapy for critically ill patients are the enteral or parenteral provision of calories, proteins, electrolytes, vitamins, trace elements and fluids. The metabolism of critically ill patients is characterized by a catabolic stress condition, which is caused by a systemic inflammatory response and is associated with an increased infection rate, occurrence of multiple organ failure and increased mortality.Traditionally, nutritional therapy has been considered as an "adjunctive" therapy for critically ill patients with the primary goal of providing energy to maintain muscle mass. Based on the scientific developments of recent years, it became evident that adequate nutritional therapy can favorably influence stress-related metabolic processes, reduce oxidative cell damage and modulate the immune response of the body. Important measures that can positively influence the clinical course of intensive care patients include early enteral nutrition, adequate intake of macro- and micronutrients, and blood glucose control.

[Consciousness disorders from toxicological view]. / Bewusstseinsstörungen aus toxikologischer Sicht.

Poisoning with impaired mental state is a frequent cause for hospital admission. The initial management includes assessment of vital functions and airway management followed by focussed diagnostics. Poison Emergency Centers can provide valuable assistance in acute intoxications. Clinically important agents causing mental state alterations include opiates, benzodiazepines, tricyclic antidepressants, alcohol, methanol and ethylene glycol, carbon monoxide and salicylates. Most important therapeutic measures comprise supportive care, decontamination or elimination. For certain toxins specific antidotes are available. In presence of severe intoxications and impaired vital functions, the patient should be transferred to the intensive care unit (ICU).