Admission Blood Glucose in the Emergency Department is Associated with Increased In-Hospital Mortality in Nontraumatic Critically Ill Patients.

BACKGROUND: Abnormal admission blood glucose was reported as a useful predictor of outcome in critically ill patients. OBJECTIVES: To identify patients at higher risk, this study aimed to evaluate the relationship between admission blood glucose levels and patient mortality during the management of nontraumatic critically ill patients in the emergency department (ED). METHODS: In this prospective, single-center observational study in a German university ED, all adult patients admitted to the resuscitation room of the ED were included between September 1, 2014 and August 31, 2015. Directly after resuscitation room admission, blood samples for admission blood glucose were taken, and adult patients were divided into groups according to predefined cut-offs between the admission blood glucose. Study endpoint was in-hospital mortality. RESULTS: During the study period, 532 patients were admitted to the resuscitation room. The data of 523 patients (98.3%) were available for analysis. The overall in-hospital mortality was 34.2%. In comparison with an in-hospital mortality of 25.2% at an admission blood glucose of 101-136 mg/dL (n = 107), admission blood glucose of ≤ 100 mg/dL (n = 25, odds ratio [OR] 6.30, 95% confidence interval [CI] 2.44-16.23, p < 0.001), 272-361 mg/dL (n = 63, OR 2.53, 95% CI 1.31-4.90, p = 0.007), and ≥ 362 mg/dL (n = 44, OR 2.96, 95% CI 1.42-6.18, p = 0.004) were associated with a higher mortality. CONCLUSIONS: Abnormal admission blood glucose is associated with a high in-hospital mortality. Admission blood glucose is an inexpensive and rapidly available laboratory parameter that may predict mortality and help to identify critically ill patients at risk in a general nontraumatic critically ill ED patient cohort. The breakpoint for in-hospital mortality may be an admission blood glucose ≤ 100 and ≥ 272 mg/dL.

Linker engineering in anti-TAG-72 antibody fragments optimizes biophysical properties, serum half-life, and high-specificity tumor imaging.

Antibody (Ab) fragments have great clinical potential as cancer therapeutics and diagnostics. Their small size allows for fast clearance from blood, low immunoreactivity, better tumor penetration, and simpler engineering and production. The smallest fragment derived from a full-length IgG that retains binding to its antigen, the single-chain variable fragment (scFV), is engineered by fusing the variable light and variable heavy domains with a peptide linker. Along with switching the domain orientation, altering the length and amino acid sequence of the linker can significantly affect scFV binding, stability, quaternary structure, and other biophysical properties. Comprehensive studies of these attributes in a single scaffold have not been reported, making design and optimization of Ab fragments challenging. Here, we constructed libraries of 3E8, an Ab specific to tumor-associated glycoprotein 72 (TAG-72), a mucinous glycoprotein overexpressed in 80% of adenocarcinomas. We cloned, expressed, and characterized scFVs, diabodies, and higher-order multimer constructs with varying linker compositions, linker lengths, and domain orientations. These constructs dramatically differed in their oligomeric states and stabilities, not only because of linker and orientation but also related to the purification method. For example, protein L-purified constructs tended to have broader distributions and higher oligomeric states than has been reported previously. From this library, we selected an optimal construct, 3E8.G4S, for biodistribution and pharmacokinetic studies and in vivo xenograft mouse PET imaging. These studies revealed significant tumor targeting of 3E8.G4S with a tumor-to-background ratio of 29:1. These analyses validated 3E8.G4S as a fast, accurate, and specific tumor-imaging agent.

Early Lactate Dynamics in Critically Ill Non-Traumatic Patients in a Resuscitation Room of a German Emergency Department (OBSERvE-Lactate-Study).

BACKGROUND: Management of critically ill non-trauma patients in the resuscitation room of an emergency department (ED) is very challenging, and it is difficult to identify patients with a higher risk of death. Previous studies have shown that lactate indices can predict survival for selected diseases and syndromes. OBJECTIVE: As reported for other patient populations, we set out to determine whether admission lactate or lactate dynamics (LD) within 24 h can predict 30-day mortality in unselected critically ill non-traumatic patients. METHODS: In this retrospective study over a 1-year period, admission lactate, time weighted average lactate (LacTW) and LD of all critically ill adult patients admitted from ED to intensive care unit were analyzed. A linear regression model was implemented to estimate lactate data 1 h after admission. RESULTS: The admission lactate, LacTW, and LD within 24 h were analyzed from 392 critically ill patients. The overall 30-day mortality rate was around 29%. Admission lactate (4.1 ± 4.0 mmol/L vs. 6.6 ± 6.1 mmol/L; p < 0.01) and LacTW (1.8 ± 1.7 mmol/L vs. 4.1 ± 4.8 mmol/L; p < 0.01) were different between survivors and non-survivors. LD between survivors and non-survivors did not differ at 1 h, 6 h, 12 h, or 24 h. After excluding patients with out-of-hospital or in-hospital cardiac arrest during resuscitation room management, admission lactate and LD between survivors and non-survivors did not differ at 1 h, 12 h, and 24 h. LD at 6 h (44% ± 42% vs. 33% ± 58%; p = 0.042) and LacTW (1.7 ± 1.6 mmol/L vs. 2.6 ± 3.0 mmol/L; p < 0.01) did differ. CONCLUSIONS: In critically ill ED patients initially requiring treatment in a resuscitation room setting, LD at 6 h and LacTW may predict their survival beyond 30 days. These findings need to be confirmed in a prospective study design.

Radiolabeling of a cyclic RGD (cyclo Arg-Gly-Asp-d-Tyr-Lys) peptide using sodium hypochlorite as an oxidizing agent.

A simple and rapid nonradioactive iodide labeling/radiolabeling method for peptides, using an inexpensive oxidizing agent such as sodium hypochlorite and a cyclic peptide, cRGDyK (cyclo Arg-Gly-Asp-d-Tyr-Lys), was developed in this work. Labeling reaction was optimized by conducting experiments under variable ratios of the reagents, the reaction times, and the pH. The study demonstrated that radiolabeling of the cyclic peptide was fast and pH independent. Monoiodinated and di-iodinated cRGDyK were formed under all conditions and varied with the ratio of the reagents and the reaction time. Total percent of the iodinated cRGDyK (monoiodinated and di-iodinated cRGDyK) varied between 44 and 100 depending on the reaction conditions. Excess cyclic peptide over equal molar ratio of sodium iodide and sodium hypochlorite yielded in predominant amounts of monoiodinated cRGDyK, ie, >60% under 2:1:1 ratio and ~88% under 5:1:1 ratio of cRGDyK:sodium iodide:sodium hypochlorite.

Elevated admission lactate levels in the emergency department are associated with increased 30-day mortality in non-trauma critically ill patients.

BACKGROUND: Elevated blood lactate levels were reported as useful predictors of clinical outcome and mortality in critically ill patients. To identify higher-risk patients, this investigation evaluated the relationship between patient mortality and admission lactate levels during the management of non-trauma critically ill patients in the emergency department (ED). METHODS: In this prospective, single centre observational study in a German university ED, all adult patients who were admitted to the ED resuscitation room were evaluated between September 1, 2014 and August 31, 2015. Blood samples for blood gas analysis, including lactate levels, were obtained immediately at admission. Study endpoint was 30-day mortality. RESULTS: During the study period, 532 patients were admitted to the resuscitation room of the ED. The data of 523 patients (98.3%) were available. The overall 30-day mortality was 34.2%. Patients presenting to the resuscitation room with admission lactate levels < 2.0 mmol/l had a 30-day mortality of 22.7%, while admission lactate levels above 8.0 mmol/l were associated with higher mortality (8.0-9.9 mmol/l: OR: 2.83, 95%CI: 1.13-7.11, p = 0.03, and ≥ 10 mmol/l: OR: 7.56, 95%CI: 4.18-13.77, p < 0.001). CONCLUSION: High lactate levels at admission are associated with an increased 24-h and 30-day mortality. These measurements may be used not only to predict mortality, but to help identify patients at risk for becoming critically ill. The breakpoint for mortality may be an ALL ≥8.0 mmol/l.

Resuscitation room management of critically ill nontraumatic patients in a German emergency department (OBSERvE-study).

BACKGROUND: Management of critically ill nontrauma (CINT) patients in the resuscitation room (RR) of the emergency department (ED) is very challenging. Detailed data describing the characteristics and management of this population are lacking. This observational study describes the epidemiology, management and outcome in CINT ED patients in the RR. PATIENTS AND METHODS: From September 2014 to August 2015, data were collected prospectively on adult CINT patients admitted to the RR of a single German University ED. Patient characteristics, out-of-hospital/in-hospital treatment, admission-related diseases, time intervals for diagnostics and interventions plus outcome were recorded using a self-developed questionnaire. RESULTS: A total of 34 303 patients were admitted to the ED; of these 21 074 patients were admitted for nontrauma emergencies and because of acute life-threatening problems. Five hundred and thirty-two CINT patients were admitted to the RR (median age: 71 years, 58.3% men). The main problems on admission were obstructed airway (3.8%, A), respiratory insufficiency (26.5%, B), shock (35.5%, C), unconsciousness (33.3%, D) or other (0.9%, E). Out-of-hospital and in-hospital management included intravenous access (96.8 vs. 76.9%), 12-lead ECG (50.0 vs. 86.5%), invasive airway management (30.1 vs. 27.1%), noninvasive and invasive ventilation (7.0 vs. 16.4% and 30.1 vs. 57.2%), catecholamines (16.2 vs. 24.1%), arterial line (0.2 vs. 58.1%) and cardiopulmonary resuscitation (18.4 vs. 12.2%). The mean length of stay was 34±24 min. At day 30, all-cause mortality was 34.2% (patients with and without cardiopulmonary resuscitation: 72.7 vs. 24.0%, P<0.001). CONCLUSION: Observation of critically ill patients in the resuscitation room of the Emergency Department shows the challenge of care for CINT patients in the ED. With high levels of mortality, there is an urgent need for structured ED management guidelines.