Background: Whether the occurrence of refeeding syndrome (RFS), a metabolic condition characterized by electrolyte shifts after initiation of nutritional therapy, has a negative impact on clinical outcomes remains ill-defined. We prospectively investigated a subgroup of patients included in a multicentre, nutritional trial (EFFORT) for the occurrence of RFS. Methods: In this secondary analysis of a randomized-controlled trial investigating the effects of nutritional support in malnourished medical inpatients, we prospectively screened patients for RFS and classified them as “RFS confirmed” and “RFS not confirmed” based on predefined criteria (i.e. electrolyte shifts, clinical symptoms, clinical context, and patient history). We assessed associations of RFS and mortality within 180 days (primary endpoint) and other secondary endpoints using multivariable regression analysis. Results: Among 967 included patients, RFS was confirmed in 141 (14.6%) patients. Compared to patients with no evidence for RFS, patients with confirmed RFS had significantly increased 180-days mortality rates (42/141 (29.8%) vs 181/826 (21.9%), adjusted odds ratio (OR) 1.53 (95% CI 1.02 to 2.29), P < .05). Patients with RFS also had an increased risk for ICU admission (6/141 (4.3%) vs 13/826 (1.6%), adjusted OR 2.71 (95% CI 1.01 to 7.27), P < .05) and longer mean length of hospital stays (10.5 ± 6.9 vs 9.0 ± 6.6 days, adjusted difference 1.57 days (95% CI 0.38–2.75), P = .01). Conclusion: A relevant proportion of medical inpatients with malnutrition develop features of RFS upon hospital admission, which is associated with long-term mortality and other adverse clinical outcomes. Further studies are needed to develop preventive strategies for RFS in this patient population.

Objectives Risk stratification in patients with infection is usually based on the Sequential Organ Failure Assessment-Score (SOFA score). Our aim was to investigate whether the vasoactive peptide mid-regional pro-adrenomedullin (MR-proADM) improves the predictive value of the SOFA score for 30-day mortality in patients with acute infection presenting to the emergency department (ED). Methods This secondary analysis of the prospective observational TRIAGE study included 657 patients with infection. The SOFA score, MR-proADM, and traditional inflammation markers were all measured at time of admission. Associations of admission parameters and 30-day mortality were investigated by measures of logistic regression, discrimination analyses, net reclassification index (NRI), and integrated discrimination index (IDI). Results MR-proADM values were higher in non-survivors compared with survivors (4.5 ± 3.5 nmol/L vs. 1.7 ± 1.8 nmol/L) with an adjusted odds ratio of 26.6 (95% CI 3.92 to 180.61, p=0.001) per 1 nmol/L increase in admission MR-proADM levels and an area under the receiver operator curve (AUC) of 0.86. While the SOFA score alone revealed an AUC of 0.81, adding MR-proADM further improved discrimination (AUC 0.87) and classification within predefined risk categories (NRI 0.075, p-value <0.05). An admission MR-proADM threshold of 1.75 nmol/L provided the best prognostic accuracy for 30-day mortality; with a sensitivity of 81% and a specificity of 75%, and a negative predictive value of 98%. Conclusions MR-proADM improved the mortality risk stratification in patients with infection presenting to the ED beyond SOFA score alone and may further improve initial therapeutic site-of-care decisions. Trial registration ClinicalTrials.gov NCT01768494. Registered January 15, 2013.

Objective: Systemic infections and sepsis lead to a strong activation of the vasopressin system, which is pivotal for stimulation of the endocrine stress response and in addition has vasoconstrictive and immunomodulatory effects. Our aim was to assess the significance of the vasopressor system through measurement of C-terminal proAVP (copeptin) regarding mortality prediction in a large prospective cohort of patients with systemic infection. Design and Methods: This secondary analysis of the observational cohort TRIAGE study included consecutive, adult, medical patients with an initial diagnosis of infection seeking emergency department care. We used multivariable regression analysis to assess associations of copeptin levels in addition to the sequential organ failure assessment (SOFA) score with 30-day mortality. Discrimination was assessed by calculation of the area under the curve (AUC). Results: Overall, 45 of 609 (7.4%) patients with infection died within 30 days. Non-survivors had a marked upregulation of the vasopressin system with a more than 4-fold increase in admission copeptin-levels compared to non-survivors (199.9 ± 204.7 vs. 46.6 ± 77.2 pmol/L). In a statistical model copeptin was significantly associated with mortality (adjusted odds ratio of 1.04, 95% CI 1.01 to 1.07, p=0.002). Regarding discrimination, copeptin alone showed an AUC of 0.82, while adding copeptin to the SOFA score significantly improved its prognostic ability (AUC 0.83 vs. 0.86, p=0.027). Conclusion: Activation of vasopressin system mirrored by an increase in copeptin levels provided significant information regarding mortality risk and improved the SOFA score for prediction of sepsis mortality. Trial registration: ClinicalTrials.gov NCT01768494. Registered January 9, 2013