Protoporphyrin IX in serum of high-grade glioma patients: A novel target for disease monitoring via liquid biopsy.

High-grade gliomas (HGG) carry a dismal prognosis. Diagnosis comprises MRI followed by histopathological evaluation of tissue; no blood biomarker is available. Patients are subjected to serial MRIs and, if unclear, surgery for monitoring of tumor recurrence, which is laborious. MRI provides only limited diagnostic information regarding the differentiation of true tumor progression from therapy-associated side effects. 5-aminolevulinic acid (5-ALA) is routinely used for induction of protoporphyrin IX (PpIX) accumulation in malignant glioma tissue, enabling improved tumor visualization during fluorescence-guided resection (FGR). We investigated whether PpIX can also serve as a serum HGG marker to monitor relapse. Patients (HGG: n = 23 primary, pHGG; n = 5 recurrent, rHGG) undergoing FGR received 5-ALA following standard clinical procedure. The control group of eight healthy volunteers (HCTR) also received 5-ALA. Serum was collected before and repeatedly up to 72 h after drug administration. Significant PpIX accumulation in HGG was observed after 5-ALA administration (ANOVA: p = 0.005, post-hoc: HCTR vs. pHGG p = 0.029, HCTR vs. rHGG p = 0.006). Separation of HCTR from pHGG was possible when maximum serum PpIX levels were reached (CI95% of tMax). ROC analysis of serum PpIX within CI95% of tMax showed successful classification of HCTR and pHGG (AUCROC 0.943, CI95% 0.884-1.000, p < 0.001); the optimal cut-off for diagnosis was 1275 pmol PpIX/ml serum, reaching 87.0% accuracy, 90.5% positive predictive and 84.0% negative predictive value. Baseline PpIX level was similar in patient and control groups. Thus, 5-ALA is required for PpIX induction, which is safe at the standard clinical dosage. PpIX is a new target for liquid biopsy in glioma. More extensive clinical studies are required to characterize its full potential.

Emergency department overcrowding and inpatient boarding: a statewide glimpse in time.

OBJECTIVES: This was a point-prevalence study designed to quantify the magnitude of emergency department (ED) overcrowding and inpatient boarding. Every ED in Michigan was surveyed at a single point in time on a Monday evening. Given the high patient volumes on Monday evenings, the effect on inpatient boarding the next morning was also reviewed. METHODS: All 134 EDs within the state of Michigan were contacted and surveyed on Monday evening, March 16, 2009, over a single hour and again the following morning. Questions included data on annual census, bed number, number of admitted patients within the ED, ambulance diversion, and ED length of stay. RESULTS: Data were obtained from 109 of the 134 (81%) hospitals on Monday evening and 99 (74%) on Tuesday morning. There was no difference in annual visits or ED size between participating and nonparticipating EDs. Forty-seven percent of EDs were boarding inpatients on Monday evening, compared with 30% on Tuesday morning. The mean estimated boarding times were 3.7 hours (Monday evening) and 7.2 hours (Tuesday morning). Twenty-four percent of respondents met the definition of overcrowded during sampling times. There was a significant relationship between inpatient boarding and ED overcrowding (p < 0.001). Only three EDs were actively diverting ambulances. CONCLUSIONS: In this study on a single Monday evening, 47% of EDs in Michigan were actively boarding inpatients, while 24% were operating beyond capacity. On the following morning (Tuesday), EDs had fewer boarded inpatients than on Monday evening. However, these boarded inpatients remained in the ED for a significantly longer duration.