Utility of measuring serum creatinine to detect renal compromise in ED patients receiving IV contrast-enhanced CT scan.

OBJECTIVE: The objectives of this study are to determine the efficacy of a roster of clinical factors in identifying risk for renal insufficiency in emergency department (ED) patients requiring intravenous contrast-enhanced CT scan (IVCE-CT) and to help mitigate potential for developing contrast-induced nephropathy (CIN). METHODS: A review was conducted of consecutive ED patients who received IVCE-CT during a 4-month period in our urban ED. The values of ED serum creatinine (SCr) performed were tabulated. The medical records of all patients with an elevated SCr (> 1.4 mg/dL) were reviewed to determine and correlate the presence of clinical risk factors for underlying renal insufficiency. RESULTS: During the 4-month study period, there were 2260 consecutive cases who received IVCE-CT; of these, 2250 (99.6%) had concomitant measurement of SCr. Elevated SCr occurred in 141 patients (6.2%); of these, 75 had a SCr > 2 mg/dL. In all, 139/141 (98.6%) with an elevated SCr had an underlying chronic or acute medical condition identified by medical record review which potentially compromised renal function, including chronic renal disease, diabetes mellitus, HIV infection, cancer, hypertension, congestive heart failure, sepsis/septic shock, chronic alcoholism, and sickle cell disease. Two patients with no identified risk factor each had (mildly) elevated SCr; both had a normal SCr measured post-CT scan. The total cost of performing serum basic metabolic panel to measure SCr in all patients during the 4-month study period was $94,500. CONCLUSIONS: Elevated SCr is rarely present in ED patients without recognized risk factors who receive IVCE-CT scan. The vast majority with underlying renal insufficiency are readily identified by a review of the patient's medical history and/or clinical findings. Routine SCr measurement on all ED patients regardless of risk stratification prior to IVCE imaging is neither time nor cost-effective.

GPR75: A Newly Identified Receptor for Targeted Intervention in the Treatment of Obesity and Metabolic Syndrome.

Metabolic syndrome increases the risk of stroke, cardiovascular disease, and diabetes. The morbidity and mortality associated with this constellation of risk factors are equally alarming when considering the economic and global significance that this epidemic has on an institutional and patient level. Despite several current treatments available, there needs to be a continuous effort to explore more specific and effective druggable entities for preventative and therapeutic interventions. Within this context, the G-protein coupled receptor, GPR75, is an attractive pharmacological target. GPR75 and its association with its ligand, 20-hydroxyeicosatetraenoic acid, have been shown to promote hypertension, inflammation, obesity, and insulin resistance. This review will help shed light on this novel signaling pathway and offer a perspective on a promising new direction of targeting different aspects of the metabolic syndrome involving GPR75. Gene targeting of GPR75 is more effective than current pharmacologic therapies without the known side effects.

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review.

Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21's associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis. This emerging pharmaceutical compound has shown promise in treating liver fibrosis and inflammation linked to nonalcoholic steatohepatitis. The ENTRIGUE trial, a phase 2 clinical trial of PGZ, has demonstrated a 57% reduction in triglyceride level compared to placebo; a 45% reduction in liver hepatic steatosis; improved insulin sensitivity; reductions in nonhigh-density lipoprotein-cholesterol; and reductions in apolipoprotein B-100.

Utility Of An Emergency Department Clinical Protocol For Early Identification of Coronavirus Infection.

INTRODUCTION: We assessed the utility of an emergency department (ED) protocol using clinical parameters to rapidly distinguish likelihood of novel coronavirus 2019 (COVID-19) infection; the applicability aimed to stratify infectious-risk pre-polymerase chain reaction (PCR) test results and accurately guide early patient cohorting decisions. METHODS: We performed this prospective study over a two-month period during the initial surge of the 2020 COVID-19 pandemic in a busy urban ED of patients presenting with respiratory symptoms who were admitted for in-patient care. Per protocol, each patient received assessment consisting of five clinical parameters: presence of fever; hypoxia; cough; shortness of breath/dyspnea; and performance of a chest radiograph to assess for bilateral pulmonary infiltrates. All patients received nasopharyngeal COVID-19 PCR testing. RESULTS: Of 283 patients studied, 221 (78%) were PCR+ and 62 (22%) PCR-. Chest radiograph revealed bilateral pulmonary infiltrates in 85%, which was significantly more common in PCR+ (94%) vs PCR- (52%) patients (P < 0.0001). The rate of manifesting all five positive clinical parameters was significantly greater in PCR+ (63%) vs PCR- (6.5%) patients (P < 0.0001). For PCR+ outcome, the presence of all five positive clinical parameters had a specificity of 94%, positive predictive value of 98%, and positive likelihood ratio of 10. CONCLUSIONS: Using an ED protocol to rapidly assess five clinical parameters accurately distinguishes likelihood of COVID-19 infection prior to PCR test results, and can be used to augment early patient cohorting decisions.

Developing an emergency department order set to treat acute pain in sickle cell disease.

STUDY OBJECTIVE: Patients with sickle cell disease (SCD) have many emergency department visits because of painful vaso-occlusive episodes (VOE). Guidelines recommend treatment within 30 minutes of triage, but this is rarely achieved in clinical practice. Our goal was to develop an order set that is being implemented in the ED to facilitate and standardize emergency care for SCD patients in acute pain from VOEs presenting to the emergency department (ED) in New York City (NYC). METHODS: Using a RAND/University of California, Los Angeles modified Delphi panel, we convened a multidisciplinary panel and reviewed evidence on how to best manage SCD pain in the ED. Panelists collaboratively developed then rated 202 items that could be included in an ED order set. RESULTS: A consensus order set, a practical how-to guide for managing SCD pain in the ED, was developed based on items that received high median ratings. CONCLUSIONS: The management of acute pain experienced during VOEs is critical to patients with SCD; ED order sets, such as this one, can help standardize pain management, including at triage, evaluation, discharge, and follow-up care. After implementation in NYC EDs, studies to examine changes in quality care metrics (eg, wait times, readmissions) are planned.

Identification of an alternate delta-globin mRNA in adult human erythroid cells.

Here we describe the identification and characterization of an alternate delta-globin mRNA (Alt-d) discovered during high-throughput sequencing of mRNA from adult human erythroid cells. Alt-d mRNA shares the same coding region, splicing pattern, downstream untranslated region, and site of polyadenylation with the previously defined delta-globin (Delta) mRNA. Alt-d mRNA encodes an additional 145 nt in the upstream untranslated region, suggesting an alternative site of transcriptional initiation and transcription through the previously defined promoter, which contains several protein-binding motifs and a TATA box. Northern blot and PCR analyses demonstrated a restricted expression of Alt-d in fetal liver, bone marrow, and adult reticulocytes. Quantitative PCR demonstrated an Alt-d expression pattern similar to that of the Delta transcripts. In addition to intergenic RNA species and the dominant delta-globin transcripts, these data suggest that a third form of RNA is produced from low-level transcription through the delta-globin gene promoter.

Fetal hemoglobin modulation during human erythropoiesis: stem cell factor has "late" effects related to the expression pattern of CD117.

A cytokine-screening assay of cultured peripheral blood cells obtained using immune rosetting and separation of progenitors was developed to identify determinants of fetal hemoglobin (HbF) modulation during adult erythropoiesis. Among the 12 erythroid growth-promoting cytokines tested, stem cell factor (SCF) at a concentration of 50 ng/mL resulted in the most significant increase in cell proliferation and HbF content. The average HbF/hemoglobin A (HbA) ratio was 30.9% +/- 18.7% in cultures containing SCF compared with 4.1% +/- 2.2% in those grown with erythropoietin (EPO) alone (P = 8.5E-8). To further investigate the hemoglobin-modulating effects of SCF, we examined the surface expression pattern of the SCF receptor, CD117, among maturing erythroblasts. CD117 expression increased during the first week of culture and peaked on culture days 7 to 9. After culture day 9, the level of CD117 declined to lower levels. The rise in CD117 expression to high levels mirrored that of the transferrin receptor (CD71), and the subsequent reduction in CD117 was inversely related to increases in expression of glycophorin A. SCF-related increases in the HbF/HbA ratio correlated with the expression pattern of CD117. SCF added during days 7 to 14 resulted in a more pancellular distribution of HbF on day 14 compared with the heterocellular distribution present in cultures supplemented with SCF on days 0 to 7. A significant SCF-mediated increase in HbF was also measured using progenitors derived from cord blood. These results suggest that the HbF response to SCF is greatest at the late progenitor stage as a function of surface CD117 expression.