Point-of-care lactate: a predictor of emergency medicine resource use and outcomes in infants with diarrhea

Purpose Fluid therapy for diarrhea-induced dehydration inadvertently increases emergency department length of stay (EDLOS). To prevent this delay, we investigated the usefulness of triage using point-of-care (POC) lactate in infants with diarrhea. Methods This study was performed on infants with diarrhea who visited the emergency department from January 2019 through December 2020. According to the POC lactate concentration and the Korean Triage and Acuity Scale (KTAS) level, the infants were separately divided into the low (< 2 mmol/L), moderate (2-3.9), and high (≥ 4) lactate groups and the mild (KTAS 4-5) and severe (1-3) groups, respectively. Using these 2 group designations, we compared variables regarding the emergency medicine resource use and outcomes. To predict the prolonged EDLOS (≥ median value) we performed logistic regression and receiver operating characteristic analyses. Results A total of 540 infants were included. The median of EDLOS was 169 minutes (interquartile range, 103-220). Fluid therapy was more frequently performed in the high lactate group than in the low-moderate lactate groups (85.0% vs. 60.4%-73.6%; P = 0.025). The high lactate and severe groups respectively showed higher rates of hospitalization (40.0% vs. 3.8%-7.6% [P < 0.001] and 10.9% vs. 1.4% [P = 0.015]), and longer median EDLOS (259 minutes vs. 147-178 [P < 0.001] and 185 vs. 131 [P = 0.001]) compared to the low-moderate lactate and mild groups. Compared to the KTAS, lactate is more strongly associated with the prolonged EDLOS (lactate, adjusted odds ratio, 4.80 [95% confidence interval, 1.87-15.34] vs. KTAS, 3.52 [1.90-6.54]). The areas under curve for lactate and for the KTAS were 0.66 (0.60-0.73) and 0.62 (0.55-0.69), respectively (P = 0.058). Conclusion In infants with diarrhea, POC lactate can be a predictor of emergency medicine resource use and outcomes

Identification and Characterization of a Dual-Acting Antinematodal Agent against the Pinewood Nematode, Bursaphelenchus xylophilus

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca2+ channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound

Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000-2005

The prevalence of toxigenic Clostridium difficile in Korea has been reported to be approximately 60-80%. Although the prevalence of the tcdA(-)tcdB(+) C. difficile strain was less then 5% prior to the year 2000, it has become an emerging nosocomial pathogen in Korea. Therefore, we have attempted to determine the multicentre nationwide prevalence of tcdA(+)tcdB(+) and tcdA(-)tcdB(+) C. difficile for epidemiological purposes. C. difficile strains (n=724, 30 from 2000, 80 from 2001, 74 from 2002, 76 from 2003, 179 from 2004, 285 from 2005) were obtained retrospectively from January 2000 to December 2005 from in-patients at 6 hospitals, all of whom were suspected of having C. difficile-associated disease (CDAD), colitis or pseudomembranous colitis. The numbers of participating hospitals varied yearly (1 in 2000, 2 in 2001-2003, 3 in 2004, 5 in 2005). The hospitals were located in Seoul (n=4), Kyunggi Province (n=1) and Busan (n=1), Korea. PCR assays for tcdA and tcdB genes were conducted using 724 unduplicated C. difficile isolates. The mean prevalence of tcdA(+)tcdB(+) and tcdA(-)tcdB(+) C. difficile strains over the 6 years was 51.8 % (38.4-59.3%) and 25.8%(10-56.0%), respectively. The mean prevalence of tcdA(-)tcdB(+) C. difficile strains was less than 7% until 2002, but began to increase in 2003 (13.2%) and achieved a peak in 2004 (50.3%). In 2005, the mean prevalence of tcdA(+)tcdB(+) and tcdA(-)tcdB(+) C. difficile strains was 47.7% (30.9-60.3%) and 27.0% (17.6-54.8%), respectively. This nationwide epidemiological study showed that tcdA(-)tcdB(+) C. difficile strains have already spread extensively throughout Korea, and our results provide basic data regarding the controversies currently surrounding the toxigenicity of tcdA(-)tcdB(+) C. difficile. The use of enzyme immunoassays capable of detecting both TcdA and TcdB is strongly recommended for the diagnosis of CDAD in microbiology laboratories, in order to control the spread of the tcdA(-)tcdB(+) strains of C. difficile

Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction

BACKGROUND: We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI). METHODS: Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured. RESULTS: Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r��=��-0.57, p��<��0.001), regional wall motion score index (r��=��0.52, p��=��0.001), and global longitudinal strain (r��=��0.56, p��<��0.001). The diastolic functional indices significantly correlated with age (r��=��-0.64, p��<��0.001), LV twist (r��=��-0.39, p��=��0.02), average non-infarcted myocardial circumferential strain (r��=��-0.52, p��=��0.001), and LV end-diastolic wall stress index (r��=��-0.47, p��=��0.003 with e') but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury. CONCLUSIONS: In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function.ope

The Use of Tenaculum During Intrauterine Insemination May Not Affect the Pregnancy Outcome

Purpose: The association between tenaculum application to the cervix just before embryo transfer and lower pregnancy rate has been reported. However, studies on the use of tenaculum in intrauterine insemination (IUT) cycles are not available. This study attempted to investigate whether the use of tenaculum affects the clinical outcomes of IUI. Materials and Methods: Two hundred and thirty three CC/hMG/IUI cycles of one hundred and forty three couples were recruited at Seoul National University Hospital from October 2006 to December 2008. Mock insemination and IUI with or without tenaculum application to the cervix were also performed, and clinical pregnancy rate was compared. Results: The incidence of difficult mock insemination at the beginning of cycle was higher in the tenaculum use group (p < 0.001). No significant statistical difference in the clinical pregnancy rate was observed between the groups with or without tenaculum application (12.1% vs. 18.5%; p = 0.175), which was not influenced by the difficulty of mock insemination. Conclusion: The use of tenaculum during IUI may not affect the pregnancy outcome. Our results need to be confirmed by a prospective study in a larger population.Merviel P, 2010, FERTIL STERIL, V93, P79, DOI 10.1016/j.fertnstert.2008.09.058Badawy A, 2009, FERTIL STERIL, V92, P1355, DOI 10.1016/j.fertnstert.2008.06.013Andersen AN, 2009, HUM REPROD, V24, P1267, DOI 10.1093/humrep/dep035STRAWN E, 2005, FERTIL STERIL, V84, pS159Van Voorhis BJ, 2001, FERTIL STERIL, V75, P661Lesny P, 1999, HUM REPROD, V14, P2367Nuojua-Huttunen S, 1999, HUM REPROD, V14, P698Fanchin R, 1998, HUM REPROD, V13, P1968Lesny P, 1998, HUM REPROD UPDATE, V4, P440Lesny P, 1998, HUM REPROD, V13, P1540Hughes EG, 1997, HUM REPROD, V12, P1865Manganiello PD, 1997, FERTIL STERIL, V68, P405Ombelet W, 1997, HUM REPROD, V12, P1458Campana A, 1996, HUM REPROD, V11, P732SILVERBERG KM, 1991, FERTIL STERIL, V56, P296

Psychometric Validation of the Korean Version of Structured Interview for Post-traumatic Stress Disorder (K-SIP)

For diagnosis and management of post-traumatic stress disorder (PTSD), the easily administered assessment tool is essential. Structured Interview for PTSD (SIP) is a validated, 17-item, simple measurement being used widely. We aimed to develop the Korean version of SIP (K-SIP) and investigated its psychometric properties. Ninety-three subjects with PTSD, 73 subjects with mood disorder or anxiety disorder as a psychiatric control group, and 88 subjects as a healthy control group were enrolled in this study. All subjects completed psychometric assessments that included the K-SIP, the Korean versions of the Clinician-Administered PTSD Scale (CAPS) and other assessment tools. The K-SIP presented good internal consistency (Cronbach's α=0.92) and test-retest reliability (r=0.87). K-SIP showed strong correlations with CAPS (r=0.72). Among three groups including PTSD patients, psychiatric controls, and normal controls, there were significant differences in the K-SIP total score. The potential cut-off total score of K-SIP was 20 with highest diagnostic efficiency (91.9%). At this point, the sensitivity and specificity were 95.5% and 88.4%, respectively. Our result showed that K-SIP had good reliability and validity. We expect that K-SIP will be used as a simple but structured instrument for assessment of PTSD

Serum Levels of Advanced Glycation End Products Are Associated with In-Stent Restenosis in Diabetic Patients

The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (>170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (≤170 U/ml) (19.6%) (p<0.001). Furthermore, multivariate analysis revealed that a high level of serum AGEs is an independent risk factor for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The serum levels of AGEs constitute an excellent predictive factor for ISR, and should be one of the guidelines for medical therapy and interventional strategy to prevent ISR in diabetic patients

Targeting the Lactate Transporter MCT1 in Endothelial Cells Inhibits Lactate-Induced HIF-1 Activation and Tumor Angiogenesis

Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1) pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs) thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1) that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2) and basic fibroblast growth factor (bFGF) expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities

Evaluation of Salmon, Tuna, and Beef Freshness Using a Portable Spectrometer

There has been strong demand for the development of an accurate but simple method to assess the freshness of food. In this study, we demonstrated a system to determine food freshness by analyzing the spectral response from a portable visible/near-infrared (VIS/NIR) spectrometer using the Convolutional Neural Network (CNN)-based machine learning algorithm. Spectral response data from salmon, tuna, and beef incubated at 25 &deg;C were obtained every minute for 30 h and then categorized into three states of &ldquo;fresh&rdquo;, &ldquo;likely spoiled&rdquo;, and &ldquo;spoiled&rdquo; based on time and pH. Using the obtained spectral data, a CNN-based machine learning algorithm was built to evaluate the freshness of experimental objects. In addition, a CNN-based machine learning algorithm with a shift-invariant feature can minimize the effect of the variation caused using multiple devices in a real environment. The accuracy of the obtained machine learning model based on the spectral data in predicting the freshness was approximately 85% for salmon, 88% for tuna, and 92% for beef. Therefore, our study demonstrates the practicality of a portable spectrometer in food freshness assessment

The role of hypoxia-inducible factor-1 in hyperthermia-induced tumor reoxygenation and therapy resistance

<p>Imbalance between oxygen consumption and supply often makes tumors hypoxic (Bristow and Hill 2008). Tumor hypoxia is significantly correlated with aggressive tumor growth, ineffective response to radiation and chemotherapy, and as a result, poor patient prognosis. Hyperthermia (HT) is a strong adjuvant treatment to overcome these challenges of tumor hypoxia because it causes tumor reoxygenation at temperatures lower than 43ºC (Song, Park, and Griffin 2001). However, the detailed molecular mechanisms of how HT enhances tumor oxygenation have not been elucidated. Here we determine that 1 hour HT activates hypoxia-inducible factor-1 (HIF-1) and its downstream targets, vascular endothelial growth factor (VEGF), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase 1 (PDK1) in tumors. Consistent with HIF-1 activation and upregulation of its downstream genes, HT also enhances tumor perfusion/vascularization and decreases oxygen consumption rates. As a result, tumor hypoxia is reduced after HT suggesting that these physiological changes contribute to HT-induced tumor reoxygenation. Since HIF-1 is a potent regulator of tumor vascularization and metabolism, our findings suggest that HIF-1 plays a role in HT-induced tumor reoxygenation by transactivating its downstream targets. Mechanistically, we demonstrate that NADPH oxidase-mediated reactive oxygen species (ROS) production upregulates HIF-1 after HT. Further, we determine that this pathway is initiated by increased transcription of NADPH oxidase-1 (NOX1) through the ERK pathway.</p><p>A major research effort at Duke focuses on combinations of HT and doxorubicin in the treatment of locally advanced breast and other cancers. Thus, we investigated whether there are HIF-1 responses to doxorubicin treatment. We reveal that doxorubicin also activates HIF-1. Unlike HT, doxorubicin-induced HIF-1 promotes persistent tumor angiogenesis. We also reveal that the signal transducer and activator of transcription 1 (STAT1)/inducible nitric oxide synthase (iNOS) pathway causes HIF-1&#945; accumulation in an oxygen-independent manner. We show that activated STAT1 upregulates iNOS expression and promotes nitric oxide (NO) production in tumor cells resulting in HIF-1&#945; stabilization. We further determine that both iNOS inhibitor, 1400W and STAT1 inhibitor, epigallocatechin-3-gallate (EGCG) significantly decrease intracellular NO production and suppress doxorubicin-induced normoxic HIF-1&#945; accumulation.</p><p>HIF-1 is often considered a promising therapeutic target because of its role in tumor progression (Semenza 2003) and therapy resistance (Moeller et al. 2004). However, our findings suggest that HIF-1 plays a pleiotropic role in response to HT and chemotherapy. Therefore, to preferentially take advantage of HT-induced HIF-1 activation and also to suppress its deleterious effects induced by chemotherapy or as we have previously reported, by radiation (Moeller et al. 2004), HIF-1 inhibition needs to be carefully regulated in a time-sensitive manner to achieve optimal therapeutic effects.</p>Dissertatio