Accuracy of transcutaneous carbon dioxide monitoring in hypotensive patients.

OBJECTIVES: Continuous blood gas monitoring is frequently necessary in critically ill patients. Our aim was to assess the accuracy of transcutaneous CO2 tension (PtcCO2) monitoring in the emergency department (ED) assessment of hypotensive patients by comparing it with the gold standard of arterial blood gas analysis (ABGA). METHODS: All patients receiving PtcCO2 monitoring in the ED were included. We excluded paediatric patients, patients with no ABGA results during a hypotensive event, patients whose ABGA was not performed simultaneously with PtcCO2 monitoring, and patients who received sodium bicarbonate for resuscitation. The included patients were classified into hypotensive patients and normotensive patients. A hypotensive patient was defined as a patient showing a mean arterial pressure under 60 mm Hg. The agreement in measurement between PaCO2 tension (PaCO2) and PtcCO2 were investigated in both groups. RESULTS: The mean difference between PaCO2 and PtcCO2 was 2.1 mm Hg, and the Bland-Altman limits of agreement (bias ± 1.96 SD) ranged from -15.6 to 19.7 mm Hg in the 28 normotensive patients. The mean difference between PaCO2 and PtcCO2 was 1.1 mm Hg, and the Bland-Altman limits of agreement (bias ± 1.96 SD) ranged from -19.5 to 21.7 mm Hg in the 26 hypotensive patients. The weighted κ values were 0.64 in the normotensive patients and 0.60 in the hypotensive patients. CONCLUSIONS: PtcCO2 monitoring showed wider limits of agreement with PaCO2 in urgent situations in the ED environment. However, acutely developed hypotension does not affect the accuracy of PtcCO2 monitoring.

The effect of hypertonic saline on mRNA of proinflammatory cytokines in lipopolysaccharide-stimulated polymorphonuclear cells.

BACKGROUND: Hypertonic saline is often used to resuscitate patients experiencing shock. In such conditions, polymorphonuclear cells and Toll-like receptors (TLRs) form an essential part of early induced innate immunity. OBJECTIVE: To investigate the immunomodulatory effect of hypertonic saline on polymorphonuclear cells by evaluating the changes in TLR-4 receptors and proinflammatory cytokines. METHODS: Polymorphonuclear cells were isolated from whole blood using Polymorphprep (Axis-Shield, Oslo, Norway). The isolated polymorphonuclear cells were plated at a density of 1 × 10(6) cells/mL in 6-well flat-bottomed culture plates and were stimulated with 1 µg/mL lipopolysaccharide or N-formyl-methionyl-leucyl-phenylalanine. The stimulated polymorphonuclear cells were cultured in hypertonic saline at 10, 20, or 40 mmol/L above isotonicity. After that, the changes in TLR-4 and cytokines were measured by quantitative real-time polymerase chain reaction and flow cytometry. RESULTS: The level of TLR-4 mRNA expression decreased after stimulation with N-formyl-methionyl-leucyl-phenylalanine, but hypertonic saline did not affect the TLR-4 mRNA expression. TLR-4 mRNA expression was clearly induced upon stimulation with lipopolysaccharide, and the addition of hypertonic saline restored TLR-4 mRNA expression in polymorphonuclear cells. The interleukin-1ß mRNA expression was decreased in the hypertonic environment. On the other hand, the tumor necrosis factor-α value was not influenced by the addition of hypertonic saline. CONCLUSIONS: Hypertonic saline has an immunomodulatory effect on polymorphonuclear cells through the TLR-4 pathway, and the interleukin-1ß-associated pathway is influenced more by hypertonic saline than is the tumor necrosis factor-α-associated pathway.

The mortality of patients with sepsis increases in the first month of a new academic year.

Objective: Many studies have examined the July effect. However, little is known regarding the July effect in sepsis. We hypothesized that the July effect would result in worse outcomes in patients with sepsis. Methods: Prospectively collected patients with sepsis between January 2018 and December 2021 were used. In Korea, the new academic year starts on March 1, so the "July effect" appears in March. The primary outcome was 30-day mortality. Secondary outcomes included adherence to the Surviving Sepsis Campaign bundle. Outcomes were compared between March and other months. Multivariate Cox proportional hazard regression was performed to adjust confounders. Results: Total 843 patients were included. There were no significant differences in sepsis severity. The 30-day mortality in March was higher (49% vs. 28.5%; P < 0.001). However, there was no difference in bundle adherence in March (42.2% vs. 48.0%; P = 0.264). Multivariate Cox proportional hazard regression showed that July effect was associated with mortality in patients with sepsis [adjusted hazard ratio, 1.925; 95% confidence interval, 1.405-2.638; P < 0.001]. Conclusion: July effect was associated with 30-day mortality in patients with sepsis. However, bundle adherence was not different. These results suggest that the increase in mortality during the turnover period may be related to unmeasured in-hospital management. Intensive supervision and education of residents in care of patients with sepsis is needed in the beginning of training.

Association of prehospital advanced airway and epinephrine with survival in patients with out-of-hospital cardiac arrest.

Survival benefits of prehospital advanced airway and epinephrine in out-of-hospital cardiac arrest (OHCA) patients are controversial, but few studies evaluated this together. This study evaluated association of prehospital advanced airway and epinephrine with survival outcomes in OHCA patients. This was observational study using a prospective multicentre KoCARC registry. Adult OHCA patients between October 2015 and December 2021 were included. The variables of interest were prehospital managements, which was classified into basic life support (BLS)-only, BLS + advanced airway, and BLS + advanced airway + epinephrine. In total, 8217 patients were included in analysis. Survival to discharge and good neurological outcomes were lowest in the BLS + advanced airway + epinephrine group (22.1% in BLS-only vs 13.2% in BLS + advanced airway vs 7.5% in BLS + advanced airway + epinephrine, P < 0.001 and 17.1% in BLS-only vs 9.2% in BLS + advanced airway vs 4.3% in BLS + advanced airway + epinephrine, P < 0.001, respectively). BLS + advanced airway + epinephrine group was less likely to survive to discharge and have good neurological outcomes (aOR 0.39, 95% CI 0.28-0.55, P < 0.001 and aOR 0.33, 95% CI 0.21-0.51, P < 0.001, respectively) than BLS-only group after adjusting for potential confounders. In prehospital settings with intermediate EMS providers and prehospital advanced airway insertion is performed followed by epinephrine administration, prehospital management with BLS + advanced airway + epinephrine in OHCA patients was associated with lower survival to discharge rate compared to BLS-only.

Successful resuscitation of refractory ventricular fibrillation with double sequence defibrillation.

In cardiac arrest, if the initial rhythm is ventricular fibrillation (VF) or pulseless ventricular tachycardia, the survival rates are high and good neurologic outcomes are expected. However, the mortality rate increases when refractory ventricular fibrillation (RVF) occurs. We report a case of RVF that was successfully resuscitated with double sequence defibrillation (DSD). A 51-year-old man visited the emergency department with chest pain. The initial electrocardiography showed markedly elevated ST-segment on V1-V5 leads, and VF arrest occurred. Although 10 defibrillations were administered over 20 minutes, there was no response. Two rounds of DSD were performed by placing additional pads on the patient's anterior-posterior areas and sequentially applying the maximum energy setting. The patient returned to spontaneous circulation and was discharged with cerebral performance category 1 after 14 days of hospital admission. Therefore, DSD could be an option for treatment and termination of RVF.

Assessing the severity of pulmonary embolism among patients in the emergency department: Utility of RV/LV diameter ratio.

BACKGROUND: Acute pulmonary embolism (APE) is a major cause of death from cardiovascular disease. Right ventricular systolic dysfunction (RVD) caused by APE is closely related to a poor outcome. Early risk stratification of APE is a vital step in prognostic assessment. The objective of this study was to investigate the usefulness of computed tomographic pulmonary angiography (CTPA) measured right ventricular (RV)/ left ventricular (LV) diameter ratio by the emergency department (ED) specialists for early risk stratification of APE patients in ED. METHODS: The retrospective data of 229 APE patients were reviewed. Two ED specialists measured both RV and LV diameters on a single transverse scan perpendicular to the long axis of the heart. The patients were divided into two groups, RV/LV diameter ratio <1 and ratio >1. CTPA measured RV/LV diameter ratio were analyzed and compared with sPESI score, cardiac biomarkers such as N-Terminal Pro-B-Type Natriuretic Peptide (NT-pro-BNP), high sensitivity cardiac troponin T (hs-cTnT), and RVD measured by echocardiography (Echo). RESULTS: The mean age in RV/LV > 1 group was significantly higher than that of the other group (67.81±2.7 years vs. 60.68±3.2 years). Also, there were more hypertension patients (44.4% vs. 33.3%), and mean arterial pressure (MAP) was lower. A significantly higher ICU admission rate (28.05% vs. 11.61%) was shown in RV/LV >1 group, and five patients expired only in RV/LV > 1 group. RVD by Echo demonstrated the highest sensitivity, specificity, and negative predictive value (NPV) (values of 94.3%, 81.1%, 95.5%). RV/LV >1 diameter ratio by CTPA showed usefulness equivalent to cardiac biomarkers. RV/LV >1 patients' cardiac enzymes were higher, and there were more RVD in RV/LV >1 group. CONCLUSION: Simple measurement of RV/LV diameter ratio by ED specialist would be a help to the clinicians in identifying and stratifying the risk of the APE patients presenting in the ED.

Clinical Value of Whole Blood Procalcitonin Using Point of Care Testing, Quick Sequential Organ Failure Assessment Score, C-Reactive Protein and Lactate in Emergency Department Patients with Suspected Infection.

We investigated the clinical value of whole blood procalcitonin using point of care testing, quick sequential organ failure assessment score, C-reactive protein and lactate in emergency department patients with suspected infection and assessed the accuracy of the whole blood procalcitonin test by point-of-care testing. Participants were randomly selected from emergency department patients who complained of a febrile sense, had suspected infection and underwent serum procalcitonin testing. Whole blood procalcitonin levels by point-of-care testing were compared with serum procalcitonin test results from the laboratory. Participants were divided into two groups-those with bacteremia and those without bacteremia. Sensitivity, specificity, positive predictive value, negative predictive value of procalcitonin, lactate and Quick Sepsis-related Organ Failure Assessment scores were investigated in each group. Area under receiving operating curve of C-reactive protein, lactate and procalcitonin for predicting bacteremia and 28-day mortality were also evaluated. Whole blood procalcitonin had an excellent correlation with serum procalcitonin. The negative predictive value of procalcitonin and lactate was over 90%. Area under receiving operating curve results proved whole blood procalcitonin to be fair in predicting bacteremia or 28-day mortality. In the emergency department, point-of-care testing of whole blood procalcitonin is as accurate as laboratory testing. Moreover, procalcitonin is a complementing test together with lactate for predicting 28-days mortality and bacteremia for patients with suspected infection.

The Effects of Oxygen and Treatments in Hypoxic Conditions in SH-SY5Y Cells.

Many patients are admitted to the emergency department due to trauma. Patients with massive hemorrhage and respiratory failure can fall into hypovolemic shock. Thereafter, oxygen is an essential part of the treatment of trauma patients, but the mechanisms of its effects in the management of trauma patients remain unknown. Therefore, we conducted an experiment to apply hypoxia, hyperoxia, and other treatment with the goal of decreasing hypoxic neuronal cells damage, as reflected by cell survival, apoptosis, hydrogen peroxide (H2O2) production, and hypoxia-inducible factor 1α (HIF) expression in SH-SY5Y cells. Under hypoxic insults, cell survival percentages decreased and apoptosis was seen with increased necrotic cell death. High-pressure oxygen (80% O2) had no effect compared with normal-pressure oxygen (20% O2). After exposure to hypoxia, H2O2 production and levels of HIF significantly increased compared with normoxia. However, when pentoxifylline (PTX), steroid, and hypertonic saline (HTS) were added after exposure to hypoxic conditions, the production of H2O2 and HIF levels significantly decreased in the groups treated with PTX and HTS. That is, the neuroprotective effect of PTX and HTS alleviated the impacts of hypoxic insulted on neuronal cells.

Nonintegrating Direct Conversion Using mRNA into Hepatocyte-Like Cells.

Recently, several researchers have reported that direct reprogramming techniques can be used to differentiate fibroblasts into hepatocyte-like cells without a pluripotent intermediate step. However, the use of viral vectors for conversion continues to pose important challenges in terms of genome integration. Herein, we propose a new method of direct conversion without genome integration with potential clinical applications. To generate hepatocyte-like cells, mRNA coding for the hepatic transcription factors Foxa3 and HNF4α was transfected into mouse embryonic fibroblasts. After 10-12 days, the fibroblasts converted to an epithelial morphology and generated colonies of hepatocyte-like cells (R-iHeps). The generated R-iHeps expressed hepatocyte-specific marker genes and proteins, including albumin, alpha-fetoprotein, HNF4α, CK18, and CYP1A2. To evaluate hepatic function, indocyanine green uptake, periodic acid-Schiff staining, and albumin secretion were assessed. Furthermore, mCherry-positive R-iHeps were engrafted in the liver of Alb-TRECK/SCID mice, and we confirmed FAH enzyme expression in Fah1RTyrc/RJ models. In conclusion, our data suggest that the nonintegrating method using mRNA has potential for cell therapy.

The inflammatory response of neutrophils in an in vitro model that approximates the postcardiac arrest state.

PURPOSE: Postcardiac arrest syndrome (PCAS) shares many features with sepsis including plasma cytokine elevation with dysregulation of cytokine production, and the presence of endotoxin in plasma. PCAS is closely related to ischemia-reperfusion injury. During ischemia-reperfusion injury, neutrophil, which is the first line of innate immunity, plays a major role. In this study, we investigated the inflammatory response of human neutrophils in an in vitro model which we simulated with hypoxia-normoxia and hypoxia-hyperoxia environments. METHODS: After separation of neutrophils from the whole blood, they were divided into 3 experimental groups: normoxia-normoxia, hypoxia-normoxia, and hypoxia-hyperoxia groups. The production of H2O2, the expression of Toll-like receptor 4 (TLR4) receptor, and the extent of apoptosis of the neutrophils were checked. RESULTS: The in vitro hypoxia-normoxia and -hyperoxia models, which simulated the PCAS, showed initiation of the neutrophils' inflammatory reaction by hypoxia insult. Lipopolysaccharide amplifies such inflammation; therefore, prevention of secondary infection may be critical in postresuscitation patients. Temporary hyperoxia following hypoxic insult showed no difference in inflammatory reaction compared with hypoxia-normoxia. Rather, temporary hyperoxia may suppress or minimize inflammation by attenuation of TLR4 receptor. CONCLUSION: It is well known that continuous hyperoxygenation after successful cardiac arrest harms patients, but temporary hyperoxygenation with 100% O2 in a clinical situation may be helpful.

Macrophage migration inhibitory factor levels correlate with an infection in trauma patients.

BACKGROUND: The role of migration inhibitory factor (MIF) is best understood in septic shock and septic disease; however, the role of MIF in a secondary infection after trauma has not yet been completely studied. This study aimed to evaluate the role of MIF in trauma patients. METHODS: The patients in the study population were divided into two groups according to the results of their MIF levels. The initial MIF levels, trauma mechanism, revised trauma score, survival rate, length of stay (LOS) in the intensive care unit (ICU), level of leukocytes, and level of C-reactive protein (CRP) were compared between the groups. RESULTS: Overall, 116 patients were enrolled from August 1, 2014 to July 31, 2015. LOS in ICU in the elevated MIF group was 5.67±7.54 days compared with 2.09±2.26 days in the normal MIF group. Further, CRP level in the elevated MIF group was higher than that in the normal MIF group. CONCLUSION: In a place such as the department of emergency medicine, it is critical and important for emergency physicians to make a proper judgment and to prepare for the worst scenario. Therefore, the utilization of MIF level in trauma patients has a possibility for assisting emergency physicians.

Simple Maturation of Direct-Converted Hepatocytes Derived from Fibroblasts.

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage. However, the function of these converted cells reserve an immature phenotype. Therefore, we modified the culture conditions of mouse direct converted hepatocytes (miHeps) to mature fetal characteristics, such as higher AFP and lower albumin (ALB) expression than primary hepatocytes. First, we generate miHeps from mouse embryonic fibroblasts (MEFs) with two transcription factors HNF4α and Foxa3. These cells indicate typical epithelial morphology and express hepatic proteins. To mature hepatic function, DMSO is treated during culture time for more than 7 days. After maturation, miHeps showed features of maturation such as exhibiting typical hepatocyte-like morphology, increased up-regulated ALB and CYP enzyme gene expression, down-regulated AFP expressions, and acquired hepatic function over time. Thus, our data provides a simple method to mature direct converted hepatocytes functionally and these cells enable them to move closer to generating functional hepatocytes.

Satisfaction with facial laceration repair by provider specialty in the emergency department.

OBJECTIVE: We compared patient satisfaction with scarring after facial laceration repair in the emergency department (ED) based on the specialty of the provider. METHODS: Patients with facial lacerations admitted to the ED from 2009 to 2013 were divided into two groups. One group of patients underwent repair by an emergency physician (EP) and the other by a plastic surgeon (PS). From August 2014 to September 2014, we randomly selected 10% of all patients and assessed their degree of satisfaction with scarring over the phone using a 5-point Likert scale. RESULTS: The male to female ratio was 2.81 in the EP group and 2.05 in PS (P<0.001). The proportion of those aged 0 to 9 years among all the patients was higher in the PS group than in the EP group (50.8% vs. 30.1%, respectively, P<0.001). The duration of ED stay was 107.8±84.6 minutes in the EP group and 225.9 ± 161.8 minutes in the PS group (P<0.001). Among these patients, 228 responded to a telephone survey. A poor satisfaction score of 1 to 2 was more common in female or young patients who underwent repair by an EP (P<0.05). However, the overall satisfaction among all respondents did not differ between the two groups. CONCLUSION: Although female patients and the guardians of young children who underwent simple facial laceration repair by a PS were more satisfied than those treated by an EP, the satisfaction of the entire group of patients did not differ according to the treatment provider.

Hospital-based influenza morbidity and mortality surveillance system for influenza-like illnesses: a comparison with national influenza surveillance systems.

The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals' ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011-2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.

The use of transcutaneous CO2 monitoring in cardiac arrest patients: a feasibility study.

BACKGROUND: Prediction of the return of spontaneous circulation (ROSC) in cardiac arrest patients is a parameter for deciding when to stop cardiopulmonary resuscitation (CPR) or to start extracorporeal CPR. We investigated the change in transcutaneous PCO2 (PtcCO2) in cardiac arrest patients. METHODS: This study was carried out as a retrospective chart review. Patients with out-of-hospital cardiac arrest or in-hospital cardiac arrest within the emergency department were included. PtcCO2 monitoring with a V-Sign™ combined monitor (SenTec Inc., Therwil, Switzerland) was applied to patients at the start of CPR. We divided the included patients into the ROSC group and the no ROSC group. The ROSC group was subdivided into those achieving ROSC <15 min CPR and >15 min CPR. The change in the PtcCO2 value was analyzed at 0 min, 5 min, 10 min, and 15 min from PtcCO2 stabilization and was compared among the groups. RESULTS: A total of 42 patients were enrolled. Twenty-eight patients achieved ROSC; 13 patients achieved ROSC <15 min CPR and 15 patients achieved ROSC >15 min CPR. Fourteen patients expired without ROSC. The absolute values of PtcCO2 was lower in the ROSC group than in the no ROCS group. The PtcCO2 change over time had a tendency to decrease or to remain constant in the ROSC groups. In contrast, all patients in the no ROSC group experienced an increase in the PtcCO2 change during CPR except one case. CONCLUSIONS: PtcCO2 monitoring provides non-invasive, continuous, and useful monitoring in cardiac arrest patients.

Effects of hypertonic saline on macrophage migration inhibitory factor in traumatic conditions.

Trauma-induced suppression of cellular immune function contributes to sepsis, multiple organ dysfunction syndrome (MODS) and mortality. Macrophage migration inhibitory factor (MIF) has been revealed to be central to several immune responses. However, the role of MIF in trauma-like conditions is unknown. Therefore, the present study evaluated MIF in macrophages and polymorphonuclear neutrophils (PMNs). The effects of hypertonic saline (HTS) on lipopolysaccharide (LPS)-induced MIF levels were evaluated in macrophages. MIF concentrations were determined by an enzyme-linked immnosorbent assay (ELISA) and cell lysates were used for western blot analysis. The effects of HTS on N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced MIF were evaluated in PMNs. MIF concentrations were determined by ELISA, western blotting and real time-polymerase chain reaction (RT-PCR) to determine MIF expression. MIF levels, which were measured by the ELISA, increased by 1.24±0.38 ng/ml in the supernatants of LPS-stimulated macrophages compared with the controls (0.79±0.07 ng/ml) at 2 h. HTS10 (150 mmol/l) partially restored MIF levels (0.84±0.22 ng/ml; P<0.05). Also, western blotting was performed and MIF protein levels were higher in the LPS-stimulated macrphages (20% increase in band density) compared with the controls (P<0.05). The addition of HTS decreased MIF protein expression. MIF levels in fMLP-stimulated PMN cells were unchanged compared with the controls according to the ELISA, western blotting and RT-PCR. No effects were observed following treatment with HTS. MIF concentrations and MIF expression were higher in LPS-stimulated macrophages than controls and HTS restored MIF levels to those of the controls. MIF levels were unchanged in PMNs stimulated by fMLP.

Clinician awareness of tetanus-diphtheria vaccination in trauma patients: a questionnaire study.

BACKGROUND: Most trauma patients visit the hospital via the emergency department. They are at high risk for tetanus infection because many trauma patients are wounded. Tetanus immunity in the Korean population has been revealed to be decreased in age groups over 20 years old. It is important for emergency physicians to vaccinate patients with the tetanus booster in wound management. METHODS: Questionnaires were sent to the directors of the emergency departments of resident training hospitals certified by the Korean Society of Emergency Medicine. RESULTS: Two thirds of the emergency department directors surveyed reported applying tetanus prophylaxis guidelines to more than 80% of wounded patients. However, about 45% of clinicians in the emergency departments considered giving less than half of the wounded patient tetanus booster vaccinations, and there were no distinct differences in tetanus booster vaccination rates among different age groups. Most emergency physicians are familiar with tetanus prophylaxis guidelines for wound management. However, more than half of the emergency department directors reported that the major reason for not considering tetanus-diphtheria vaccination was due to assumptions that patients already had tetanus immunity. CONCLUSION: Attitude changes should be encouraged among emergency physicians regarding tetanus prophylaxis. As emergency physicians are frequently confronted with patients that are at a high risk for tetanus infection in emergency situations, they need to be more informed regarding tetanus immunity epidemiology and encouraged to administer tetanus booster vaccines.

Hypertonic saline downregulate the production level of lipopolysaccharide-induced migration inhibitory factor in THP-1 cells.

PURPOSE: Macrophage migration inhibitory factor (MIF) may serve as a general marker for systemic inflammation in septic and nonseptic acute critical illness. Additionally, our previous experiment has demonstrated that immunosuppressant Prostaglandin E(2) (PGE(2)) lowered MIF levels and inhibited T-cells proliferation when compared to control levels. The addition of hypertonic saline (HTS) increased MIF production as compared with PGE(2)-stimulated T-cells in concordance with restore PGE(2)-suppressed T-cells proliferation. Generally, HTS has been well known for its anti-inflammatory effect so far. Therefore, the experiments were conducted to evaluate MIF after stimulating lipopolysaccharide (LPS) either in the presence or absence of HTS in monocyte, in response to early phase injury. METHODS: Human acute monocytic leukemic cell line (THP-1) cells were cultured in RPMI media, to a final concentration of 1 × 10(6) cells/mL. The effect of HTS on LPS-induced MIF was evaluated in monocyte with 1 µg/mL LPS. HTS at 10, 20 or 40 mmol/L above isotonicity was added. MIF concentrations of the supernatant were determined by enzyme-linked immunosorbent assay, and cell lysates were used for Western blots analysis to determine the MIF expression. RESULTS: MIF concentrations in the cell supernatant increased in LPS-induced cells compared to control cells. Also, levels of MIF protein expression were higher in LPS stimulating cells. However, the addition of HTS to LPS stimulated cell restored MIF concentrations and MIF expression. CONCLUSION: The role of HTS in maintaining physiological balance in human beings, at least in part, should be mediated through the MIF pathway.