Delivery of recombinant sestrin2 ameliorates oxidative stress, mitochondrial damage and renal dysfunction in contrast-induced acute kidney injury.

Although the use of iodinated contrast agents is sometimes unavoidable for accurate diagnosis, contrast-induced acute kidney injury (CI-AKI) is a possible complication of its administration. The pathogenesis of CI-AKI has not been fully elucidated, but oxidative stress is thought to be a major factor. Sestrin2 plays an important role in cellular and mitochondrial homeostasis by regulating oxidative stress. In this study, we aimed to investigate whether recombinant adenovirus containing sestrin2 (RS) can attenuate CI-AKI by reducing oxidative stress in a CI-AKI mice model. Our results showed that RS decreases oxidative stress, pro-inflammatory cytokines (TNF-α, IL-1α, IL-1ß and IL-6) and apoptosis (Bax/Bcl2 and cleaved caspase-3) in the CI-AKI model. Additionally, RS alleviated mitochondrial damage, as evidenced by morphological changes, are restored ATP synthesis. Furthermore, RS administration resulted in a decrease in mitochondrial fission marker (Drp1) that was increased in the CI-AKI model, while the mitochondrial fusion marker (Mfn2) increased, indicating a restoration of mitochondrial dynamics. Decreased relative blood volume, as evaluated on computed tomography (CT), significantly increased compared to the CI-AKI group after RS administration. Finally, renal injury markers such as Kim-1, Ngal, IL-18 also decreased and kidney function was preserved with RS. These results suggested that RS can mitigate the deterioration of renal function in CI-AKI model.

Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure.

Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.

Predictive performance of plasma neutrophil gelatinase-associated lipocalin for neurologic outcomes in out-of-hospital cardiac arrest patients treated with targeted temperature management: A prospective observational study.

Few studies have demonstrated the prognostic potential of neutrophil gelatinase-associated lipocalin (NGAL) in post-cardiac arrest patients. This study evaluated the usefulness of plasma NGAL in predicting neurologic outcome and mortality in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). A prospective observational study was conducted between October 2013 and April 2016 at a single tertiary hospital. We enrolled 75 patients treated with TTM and collected their demographic data, cardiopulmonary resuscitation-related information, data on plasma NGAL concentration, and prognostic test results. Plasma NGAL was measured at 4 hours after return of spontaneous circulation (ROSC). The primary endpoint was the neurologic outcome at discharge and the secondary outcome was 28-day mortality. Neurologic outcomes were analyzed using a stepwise multivariate logistic regression while 28-day mortality was analyzed using a stepwise Cox regression. The predictive performance of plasma NGAL for neurologic outcome was measured by the area under the receiver operating characteristic curve and the predictability of 28-day mortality was measured using Harrell C-index. We also compared the predictive performance of plasma NGAL to that of other traditional prognostic modalities for outcome variables. Thirty patients (40%) had good neurologic outcomes and 53 (70.7%) survived for more than 28 days. Plasma NGAL in patients with good neurologic outcomes was 122.7 ±â€Š146.7 ng/ml, which was significantly lower than that in the poor neurologic outcome group (307.5 ±â€Š269.6 ng/ml; P < .001). The probability of a poor neurologic outcome was more than 3.3-fold in the NGAL >124.3 ng/ml group (odds ratio, 3.321; 95% confidence interval [CI], 1.265-8.721]). Plasma NGAL in the survived group was significantly lower than that in the non-survived group (172.7 ±â€Š191.6 vs 379.9 ±â€Š297.8 ng/ml; P = .005). Plasma NGAL was significantly correlated with 28-day mortality (hazard ratio 1.003, 95% CI 1.001-1.004; P < .001). The predictive performance of plasma NGAL was not inferior to that of other prognostic modalities except electroencephalography. Plasma NGAL is valuable for predicting the neurologic outcome and 28-day mortality of patients with OHCA at an early stage after ROSC.This study was registered at ClinicalTrials.gov on November 19, 2013 (Identifier: NCT01987466).

The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect.

As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RT-PCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.

A Delta Neutrophil Index for the Prediction of Contrast-Induced Nephropathy in Patients With St-Elevation Myocardial Infarction Followed By Percutaneous Coronary Intervention.

PURPOSE: We assessed the usefulness of the delta neutrophil index (DNI), reflecting immature granulocytes, to stratify risk for developing contrast-induced nephropathy (CIN) in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) in a clinical setting. METHODS: This study retrospectively analyzed prospective data of eligible adult patients admitted to the emergency department (ED) with STEMI followed by PCI. We determined DNI at multiple time points and analyzed the development of CIN and in-hospital mortality according to CIN incidence. RESULTS: Overall, 564 patients with STEMI followed by PCI were included. Of these, 58 patients (10.3%) had CIN. Areas under the curve for predictability of CIN using the DNI within 2 h after PCI (I) and 24 h on ED admission (24) among patients with CIN were 0.775 (P < 0.001) and 0.751 (P < 0.001), respectively. Multivariable logistic regression demonstrated that increased DNI values at time I (odds ratio [OR], 1.632; 95% confidence interval [CI], 1.357-1.964; P < 0.001) and time 24 (OR, 1.503; 95% CI, 1.272-1.777; P < 0.001) were strong independent factors for predicting CIN among patients with STEMI who underwent PCI. Increasing predictability of CIN was closely associated with DNI more than 1.8% on ED admission (OR, 12.494; 95% CI, 6.540-23.87; P < 0.001) and more than 1.9% at time 24 (OR, 10.45; 95% CI, 5.769-18.928; P < 0.001). CONCLUSION: The DNI is easily obtained as part of the complete blood count measurement without requiring additional cost or time. High DNI independently predicts the development of CIN in patients with acute STEMI followed by PCI.

Usefulness of the delta neutrophil index as an ancillary test in the emergency department for the early diagnosis of suspected acute promyelocytic leukemia.

The delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes. We evaluated the usefulness of DNI values in patients with acute myeloid leukemia (AML) to distinguish the acute stage of acute promyelocytic leukemia (APL). We analyzed patients retrospectively who were first diagnosed with AML upon admission to the emergency department (ED). Thirty of the 134 patients (22.4%) were diagnosed with APL on ED admission. The univariate analysis and multivariate logistic regression models revealed that DNI values differed significantly between APL and non-APL AML patients on days 0, 1 and 2. Increased predictability for APL was associated with a DNI greater than 24.2% on ED admission, greater than 23.6% on day 1 and greater than 44% on day 2 in patients with AML. DNI values of patients with AML could discriminate the acute stage of APL from AML for immediate initiation of all-trans retinoic acid therapy.

Possible Contrast Media Reduction with Low keV Monoenergetic Images in the Detection of Focal Liver Lesions: A Dual-Energy CT Animal Study.

OBJECTIVE: To investigate the feasibility of dual-energy CT for contrast media (CM) reduction in the diagnosis of hypervascular and hypovascular focal liver lesions (FLL). SUBJECTS AND METHODS: The Institutional Animal Care and Use Committee approved this study. VX2 tumors were implanted in two different segments of the liver in 13 rabbits. After 2 weeks, two phase contrast enhanced CT scans including the arterial phase (AP) and portal-venous phase (PVP) were performed three times with 24-hour intervals with three different concentrations of iodine, 300 (I(300)), 150 (I(150)) and 75 mg I/mL (I(75)). The mean HU and standard deviation (SD) were measured in the liver, the hypervascular portion of the VX2 tumor which represented hypervascular tumors, and the central necrotic area of the VX2 tumor which represented hypovascular tumors in 140 kVp images with I(300) as a reference standard and in monoenergetic images (between 40 keV and 140 keV) with I(150) and I(75). The contrast-to-noise ratio (CNR) for FLLs and the ratio of the CNRs (CNR(ratio)) between monoenergetic image sets with I(150) and I(75), and the reference standard were calculated. RESULTS: For hypervascular lesions, the CNR(ratio) was not statistically different from 1.0 between 40 keV and 70 keV images with I(150), whereas the CNR(ratio) was significantly lower than 1.0 in all keV images with I(75). For hypovascular lesions, the CNR(ratio) was similar to or higher than 1.0 between 40 keV and 80 keV with I(150) and between 40 keV and 70 keV with I(75).. CONCLUSIONS: With dual-energy CT, the total amount of CM might be halved in the diagnosis of hypervascular FLLs and reduced to one-fourth in the diagnosis of hypovascular FLLs, while still preserving CNRs.

Comparison of diagnostic performance between single- and multiphasic contrast-enhanced abdominopelvic computed tomography in patients admitted to the emergency department with abdominal pain: potential radiation dose reduction.

OBJECTIVES: To evaluate feasibility of radiation dose reduction by optimal phase selection of computed tomography (CT) in patients who visited the emergency department (ED) for abdominal pain. METHODS: We included 253 patients who visited the ED for abdominal pain. They underwent multiphasic CT including precontrast, late arterial phase (LAP), and hepatic venous phase (HVP). Three image sets (HVP, precontrast + HVP, and precontrast + LAP + HVP) were reviewed. Two reviewers determined the most appropriate diagnosis with five-point confidence scale. Diagnostic performances were compared among image sets by weighted-least-squares method or DeLong's method. Linear mixed model was used to assess changes of diagnostic confidence and radiation dose. RESULTS: There was no difference in diagnostic performance among three image sets, although diagnostic confidence level was significantly improved after review of triphasic images compared with both HVP images only or HVP with precontrast images (confidence scale, 4.64 ± 0.05, 4.66 ± 0.05, and 4.76 ± 0.04 in the order of the sets; overall P = 0.0008). Similar trends were observed in the subgroup analysis for diagnosis of pelvic inflammatory disease and cholecystitis. CONCLUSIONS: There is no difference between HVP-CT alone and multiphasic CT for the diagnosis of causes of abdominal pain in patients admitted to the ED without prior chronic disease or neoplasia. KEY POINTS: • There was no difference in diagnostic performance of HVP CT and multiphasic CT. • The diagnostic confidence level was improved after review of the LAP images. • HVP CT can achieve diagnostic performance similar to that of multiphasic CT, while minimizing radiation.

Diagnostic radiation exposure of injury patients in the emergency department: a cross-sectional large scaled study.

In contrast to patients with underlying cancer or chronic disease, injury patients are relatively young, and can be expected to live their natural lifespan if injuries are appropriately treated. Multiple and repeated diagnostic scans might be performed in these patients during admission. Nevertheless, radiation exposure in injury patients has been overlooked and underestimated because of the emergent nature of such situations. Therefore, we tried to assess the cumulative effective dose (cED) of injury patients in the emergency department. We included patients who visited the emergency department (ED) of a single tertiary hospital due to injury between February 2010 and February 2011. The cED for each patient was calculated and compared across age, sex and injury mechanism. A total of 11,676 visits (mean age: 28.0 years, M:F = 6,677:4,999) were identified. Although CT consisted of only 7.8% of total radiologic examinations (n=78,025), it accounted for 87.1% of the total cED. The mean cED per visit was 2.6 mSv. A significant difference in the cED among injury mechanisms was seen (p<0.001) and patients with traffic accidents and fall down injuries showed relatively high cED values. Hence, to reduce the cED of injury patients, an age-, sex- and injury mechanism-specific dose reduction strategy should be considered.

The usefulness of rapid point-of-care creatinine testing for the prevention of contrast-induced nephropathy in the emergency department.

BACKGROUND: Renal dysfunction is the most important factor to consider when predicting a patient's risk of developing contrast-induced nephropathy (CIN). Measurement of creatinine (Cr) via rapid point-of-care blood urea nitrogen/creatinine testing (POCT-BUN/Cr) to determine CIN risk could potentially reduce the time required to achieve an accurate diagnosis and to initiate and complete treatment in the emergency department (ED). The aim of our study was to compare the results of POCT-BUN/Cr and reference laboratory tests for BUN and serum Cr. MATERIALS AND METHODS: A retrospective analysis of suspected stroke patients who presented between November 2009 and November 2010, and had BUN and Cr levels measured by POCT-BUN/Cr, and the reference laboratory tests performed with the blood sample which was transferred to the central laboratory by an air-shoot system. Two assays were conducted on the whole blood (POCT) and serum (reference) by trained technicians. The time interval from arrival at the ED to reporting of the results was assessed for both assays via a computerised physician order entry system. RESULTS: The mean standard deviation (SD) interval from arrival at the ED to reporting of the results was 11.4 (4.9) min for POCT-BUN/Cr and 46.8 (38.5) min for the serum reference laboratory tests (p<0.001). Intra-class correlation coefficient (ICC) analysis demonstrated a high level of agreement (the consistency agreement) between POCT and the serum reference tests for both BUN (ICC=0.914) and Cr (ICC=0.980). CONCLUSIONS: This study suggests that POCT-BUN/Cr results correlate well with those of serum reference tests in terms of BUN and Cr levels and, in turn, predicting CIN. POCT-BUN/Cr is easily performed with a rapid turnaround time, suggesting its use in the ED may have substantial clinical benefit.

Cumulative radiation exposure during follow-up after curative surgery for gastric cancer.

OBJECTIVE: To quantify the cumulative effective dose (cED) of radiation due to repeated CT and PET/CT examinations after curative resection of gastric cancer and to assess the lifetime attributable risk (LAR) estimates based on Biological Effects of Ionizing Radiation VII models. SUBJECTS AND METHODS: Patients who underwent a curative resection for gastric cancer between January 2006 and December 2006 and were followed-up until May 2010 were included in this study. The cED was calculated by using the dose-length product values and conversion factors for quantitative risk assessment of radiation exposure. cED and LAR were compared between early and advanced gastric cancer patients and among American Joint Committee on Cancer TNM stage groups (stage I, II, and III). The nonparametric Mann-Whitney U and Kruskal-Wallis tests, followed by a post-hoc analysis with Bonferroni adjustment, were employed as part of the statistical analysis. RESULTS: The overall median cED was 57.8 mSv (interquartile range [IQR], 43.9-74.7). The cED was significantly higher in the advanced (median, 67.0; IQR, 49.1-102.3) than in the early gastric cancer group (median, 52.3; IQR, 41.5-67.9) (p < 0.001), and increased as the TNM stage increased. For radiation exposure, 62% of all patients received an estimated cED of over 50 mSv, while 11% of patients received over 100 mSv. The median LAR of cancer incidence was 0.28% (IQR, 0.20-0.40) and there were significant differences between the early gastric cancer and advanced gastric cancer group (p < 0.001) as well as among the three TNM stage groups (p = 0.015). The LAR of cancer incidence exceeded 1% in 2.4% of the patients. CONCLUSION: The cED increases proportionally along with tumor stage and, even in early gastric cancer or stage I patients, cED is much higher than that found among the general population. Considering the very good prognosis of early gastric cancer after curative surgery, the cED should be considered when designing a postoperative follow-up CT protocol.

Use of bedside sonography for diagnosing acute epiglottitis in the emergency department: a preliminary study.

OBJECTIVES: The purpose of this study was to investigate the ability of sonography to identify acute epiglottitis in the emergency department. METHODS: Fifteen patients with a final diagnosis of acute epiglottitis from indirect laryngoscopy by an otolaryngologist were enrolled in the study. To compare the normal epiglottis and acute epiglottitis, 15 healthy volunteers were assigned to a control group. The sonographic appearances of the epiglottitis and the pre-epiglottic space were recorded. The anteroposterior diameter of the epiglottis at the midpoint and both edges in a transverse view was measured in all participants. RESULTS: A statistically significant difference (P < .001) was observed in the anteroposterior diameter of the epiglottis at the midpoint and both lateral edges between the patients and healthy volunteers. However, there was overlap in the ranges for the midpoint but no overlap in both lateral edges between groups. The upper-limit value for the healthy control group was 3.2 mm at both lateral edges, whereas the cutoff values of the right and left edges were 3.7 and 3.6 mm, respectively, according to the lower-limit value for the epiglottitis group. CONCLUSIONS: The anteroposterior diameter of the epiglottis was significantly different between the patients with epiglottitis and the healthy volunteers. Because of this significant difference in the anteroposterior diameter of the epiglottis, sonography can be used as a rapid, noninvasive, and effective diagnostic tool for identifying cases of epiglottitis in the emergency department.

A case of strangulated small bowel obstruction caused by Meckel's diverticulum in an adult.

Meckel's diverticulum results from incomplete closure of the omphalomesenteric duct, and is the most common congenital anomaly of the small intestine. We present a case report of a 42-year-old patient who developed a strangulated intestinal obstruction as a complication of Meckel's diverticulum. The strangulated bowel obstruction was suggested by contrast-enhanced computed tomography. He recovered after a diverticulectomy and had no need for a small bowel resection.