LR Group Research Articles

Accuracy of the Liver Imaging Reporting and Data System in Computed Tomography and Magnetic Resonance Image Analysis of Hepatocellular Carcinoma or Overall Malignancy—A Systematic Review

The Liver Imaging Reporting and Data System (LI-RADS) categorizes observations from imaging analyses of high-risk patients based on the level of suspicion for hepatocellular carcinoma (HCC) and overall malignancy. The categories range from definitely benign (LR-1) to definitely HCC (LR-5), malignancy (LR-M), or tumor in vein (LR-TIV) based on findings from computed tomography or magnetic resonance imaging. However, the actual percentage of HCC and overall malignancy within each LI-RADS category is not known. We performed a systematic review to determine the percentage of observations in each LI-RADS category for computed tomography and magnetic resonance imaging that are HCCs or malignancies. We searched the MEDLINE, Embase, Cochrane CENTRAL, and Scopus databases from 2014 through 2018 for studies that reported the percentage of observations in each LI-RADS v2014 and v2017 category that were confirmed as HCCs or other malignancies based on pathology, follow-up imaging analyses, or response to treatment (reference standard). Data were assessed on a per-observation basis. Random-effects models were used to determine the pooled percentages of HCC and overall malignancy for each LI-RADS category. Differences between categories were compared by analysis of variance of logit-transformed percentage of HCC and overall malignancy. Risk of bias and concerns about applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Of 454 studies identified, 17 (all retrospective studies) were included in the final analysis, consisting of 2760 patients, 3556 observations, and 2482 HCCs. The pooled percentages of observations confirmed as HCC and overall malignancy, respectively, were 94% (95% confidence interval [CI] 92%-96%) and 97% (95% CI 95%-99%) for LR-5, 74% (95% CI 67%-80%) and 80% (95% CI 75%-85%) for LR-4, 38% (95% CI 31%-45%) and 40% (95% CI 31%-50%) forLR-3, 13% (95% CI 8%-22%) and 14% (95% CI 9%-21%) for LR-2, 79% (95% CI 63%-89%) and 92% (95% CI 77%-98%) for LR-TIV, and 36% (95% CI 26%-48%) and 93% (95% CI 87%-97%) for LR-M. No malignancies were found in the LR-1 group. The percentage of HCCs and overall malignancies confirmed differed significantly among LR groups 2-5 (P < .00001). Patient selection was the most frequent factor that affected bias risk, because of verification bias and case-control study design. In a systematic review, we found that increasing LI-RADS categories contained increasing percentages of HCCs and overall malignancy based on reference standard confirmation. Of observations categorized as LR-M, 93% were malignancies and 36% were confirmed as HCCs. The percentage of HCCs found in the LR-2 and LR-3 categories indicate the need for a more active management strategy than currently recommended. Prospective studies are needed to validate these findings. PROSPERO number CRD42018087441.

Safety of resuscitation with hydroxyethyl starch 130/0.4 in hemorrhagic shock rats

Objective: To evaluate the safety of resuscitation with hydroxyethyl starch 130/0.4 during the early stage of hemorrhagic shock. Methods: Total of 120 healthy male SD rats of 2 to 3 months of age were selected as the study sample (weighed from 250 to 290 g), all the rats were numbered by staining.After that, the rats were divided into 12 groups by using random number table method: sham group (S group), no liquid resuscitation group (NF group), lactated Ringer's resuscitation group (LR group), HES resuscitation group (HES group). At the same time, the LR and HES resuscitation groups were divided into five subgroups with a concentration of 7.5, 15, 30, 60 and 90 ml·kg(-1)·h(-1,) respectively.The model of uncontrollable hemorrhagic shock was created by the method of exsanguination plus tail-cuffing.Fluid resuscitation was started 30 minutes after the exsanguination and continued for 60 min after transfusion for 15 min.The observation was continued for 330 min.At the end of observation, all rats were sacrificed and blood was collected from the rats to determine the thromboelastograms and the maximum amplitude and related parameters, as well as platelet counts, blood urea nitrogen, creatinine, urinary and renal injury molecules, and neutrophil gelatinase-associated apolipoprotein levels.Rat lung tissue specimens were collected and wet weights of the right lung and dry weights after drying were measured.The data were compared by using one-way analysis of variance (ANOVA), LSD-t test or Dunnett-t test. Results: ANOVA analysis showed that there was no significant difference in mean artery pressure (MAP) values between groups at the beginning of fluid resuscitation (F=0.934, P=0.245). At the end of fluid resuscitation, the MAP of HES90 group was (40±9) mmHg, which was lower than that in other groups.Compared with other groups, the HES90 group had higher blood loss and blood transfusion rate.There was no significant differences in platelet counts between the HES group and the LR group at 330 min (t=0.987, P>0.05), but the maximal amplitude (MA) of the thrombelastogram (TEG) was lower in the HES90 group than that in the S group (t=2.354, P<0.05). No significant difference was detected in blood urea nitrogen and serum creatinine levels between the HES, LR group and the S group (t=1.098, 0.895, both P>0.05). The total amount of urinary kidney injury molecule 1 (Kim-1) in the HES90 and NF groups increased, neutrophil gelatinase-associated apolipoprotein (NGAL) concentration and urinary NGAL levels were significantly higher than those in other groups, and the difference were statistically significant (t=3.532-11.209, all P<0.05). Conclusion: Small to moderate doses of HES130/0.4 during hemorrhagic shock is more effective and safer than the same dose of LR.

Hypertonic saline resuscitation protects against kidney injury induced by severe burns in rats

BackgroundProper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400mEq/L hypertonic saline (HS) and sodium lactate Ringer’s solution (LR) in rats with kidney injury caused by burn trauma. MethodsRats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and high mobility group protein box (HMGB)-1) were also examined as serum markers. ResultsHypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1β, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group. ConclusionsThe data indicate that 400mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.

Study on the mechanism of hypertonic salt solution alleviates lung injury of rats at the early stage of severe scald

To explore the mechanism of hypertonic salt solution (HS) alleviates lung injury of rats at the early stage of severe scald. Thirty-two female Sprague-Dawley (SD) rats were randomly assigned to sham group, lactated Ringer solution (LR) group, HS200 group (200 mmol/L HS group, 1 L 200 mmol/L HS contained 955 mL LR and 45 mL 10% NaCl) and HS400 group (400 mmol/L HS group, 1 L 400 mmol/L HS contained 846 mL LR and 154 mL 10% NaCl), with 8 rats in each group. A 30% total body surface area (TBSA) III degree scalded model was reproduced by scalded on the back with 98 centigrade boiling water for 12 seconds, whereas those in the sham group were exposed to 37 centigrade water without liquid resuscitation. Rats in the three drug intervention groups were resuscitated with LR, 200 mmol/L HS and 400 mmol/L HS by caudal vein according to the Parkland formula, respectively. All rats were sacrificed at 8 hours after scald injury to harvest abdominal aorta blood and lung tissues. Interleukins (IL-6, IL-10 and IL-17) in serum were determined by enzyme-linked immunosorbent assay (ELISA). Samples from the lung tissue were used to measure malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ultraviolet spectrophotometer. Expressions of p38 mitogen-activated protein kinase (p38MAPK) and extracellular regulated protein kinase 1/2 (ERK1/2) in the lung were determined by Western Blot. The lung tissue was stained with hematoxylin and eosin (HE), and the pathological changes were observed with a light microscope. Compared with the sham group, the lung tissues in the LR group were damage obviously, which accompanied with more inflammatory cell infiltration, cell edema and pulmonary septum thickening, and the levels of IL-6, IL-10, IL-17 in serum and MDA content, the phosphorylation of p38MAPK and ERK1/2 in lung tissues were increased whereas the activity of SOD was decreased. Compared with the LR group, the lung injury was significantly alleviated, the levels of IL-6, IL-17 in serum and MDA content and the phosphorylation of p38MAPK and ERK1/2 were decreased, and the levels of IL-10 and SOD were increased in both HS groups with a dose-dependent manner. There were significant difference in above parameters between HS400 group and LR group [serum IL-6 (ng/L): 3.76±0.12 vs. 6.72±0.90, serum IL-10 (ng/L): 33.76±3.71 vs. 16.77±3.19, serum IL-17 (ng/L): 103.52±2.78 vs. 124.96±4.96, lung MDA (nmol/mg): 5.59±0.24 vs. 7.09±0.39, lung SOD (U/mg): 226.7±3.9 vs. 172.7±3.4, lung phosphorylation of p38MAPK (p-p38MAPK)/p38MAPK: 0.15±0.09 vs. 0.35±0.19, lung phosphorylation of ERK1/2 (p-ERK1/2)/ERK1/2: 0.27±0.01 vs. 0.70±0.01, all P < 0.01]. HS protected against lung injury induced by severe burns in rats with a dose-dependent manner, and it was better than LR, and its possible mechanism was related with reducing the expression of p38MAPK and ERK1/2 pathway in lung tissue, increasing the level of anti-inflammatory cytokines and decreasing the release of pro-inflammatory cytokines, thus inhibiting excessive inflammation and oxidative stress injury in lung.

Labral Preservation: Outcomes Following Labrum Augmentation Versus Labrum Reconstruction

The purpose of this study was to compare the clinical outcomes and patient satisfaction between patients with previous surgeries who underwent hip labral augmentation versus labral reconstruction surgery. From 2006 to 2014, all patients with previous labral procedures who underwent subsequent labral augmentation by the senior surgeon were included. Patients with joint space ≤2mm and lateral center edge angle <20° and who refused to participate in follow-up were excluded. Patients who underwent labral augmentation, preserving macroscopically healthy native labral tissue and adding iliotibial band graft to increase labral volume, were compared with a matching group (1:2) of patients who underwent labral reconstruction where damaged or absent native labral tissue was replaced by the graft. Hip Outcome Score-Activity of Daily Living (HOS-ADL) was the primary outcome measure. Secondary outcomes included the modified Harris Hip Score (mHHS), HOS for Sports (HOS-Sport), Short Form-12, Western Ontario and McMaster Universities Osteoarthritis Index, and patient satisfaction with outcome. Nonparametric statistics were used to compare groups. Thirty-three patients (12 males, 21 females) who underwent labral augmentation (LA group) were compared with 66 (24 males, 42 females) labral reconstruction patients (LR group). The average age was 29 ± 10years in both groups. Six patients (18%) required revision arthroscopy in the LA group, and 9 patients (14%) in the LR group (P=.563). One patient (3%) in the LA group required a total hip arthroplasty, and 3 patients in the LR group (4.5%) had a total hip arthroplasty (P= .99). Of the remaining 26 patients in the LA group and 53 patients in the LR group, minimum 2-year follow-up was available for 21 (81%) and 51 (96%), respectively. Postoperatively the HOS-ADL, HOS-Sport, mHHS, and Western Ontario and McMaster Universities Osteoarthritis Index were significantly higher in the LA group (P< .05). The percentage of patients who reached minimum clinically important difference was significantly higher in the LA group for HOS-ADL (P= .002) and HOS-Sport (P= .008); however, there was no difference for the mHHS (P= .795). Patient satisfaction was 10 and 8 in the LA group and LR group, respectively (P= .585). In patients with previous procedures, the labral augmentation technique with preservation of macroscopically healthy native labral fibers resulted in significantly better outcomes compared with the segmental labral reconstruction procedure where damaged or previously removed labrum was replaced by a graft. Level III, comparative case series.

Anaplastic transition within the cancer microenvironment in early-stage oral tongue squamous cell carcinoma is associated with local recurrence.

The cancer microenvironment (CME) promotes malignant progression of cancer cells by stimulating cell growth, migration and invasion. Cancer-associated fibroblasts(CAFs), prominent features of the CME, interact directly with cancer cells and facilitate epithelial-mesenchymal transition(EMT). The present study examined the spatial distribution of CAFs and EMT on cancer cells in patients with early-stage tongue squamous cell carcinoma(TSCC) and their association with local recurrence. The present study included 14patients with early-stage TSCC who hadundergone glossectomy between 2006 and 2015, of which 7experienced local recurrence (LR group) and 7 did not (control group). Multiple immunofluorescent analysis (MIA) of PCNA, αSMA, vimentin, E-cadherin and cytokeratin14(CK14) was performed on slides obtained from surgical specimens to identify the expression of various cell-specific markers. The number of CAFs in the CME was significantly increased in the LR group (P=0.001). Furthermore, the neighbouring cancer cells were positive for vimentin expression, indicating EMT. However, the present study also identified concurrent expression of CK14 in all vimentin-positive cancer cells, whilst epithelial markers, including E-cadherin, were expressed in certain vimentin-positive cancer cells. Concurrent expression of CK14 and vimentin is not defined as EMT or partial EMT. Therefore, the present study proposed a novel mechanism of anaplastic transition (APT), in which epithelial cancer cells concurrently develop mesenchymal features, which is achieved by pathways other than EMT. APT is characterized such that epithelial cancer cells differentiate into more primitive states, which is different from EMT or partial EMT, and it may be associated with LR. The concept aids in improving knowledge regarding tumor recurrence in patients with early-stage TSCC.

Does Intravenous Lactated Ringer’s Solution Raise Serum Lactate?

BackgroundSerum lactate increases in states of severe sepsis and shock, but its interpretation may be subject to confounders. Lactated Ringer's solution (LR) is used in the resuscitation of septic patients and contains 28 mmol/L of sodium lactate. ObjectivesWe sought to determine if a bolus of 30 mL/kg of LR increases serum lactate levels. MethodsIn this double-blind, randomized controlled trial, 30 volunteers were assigned to receive either 30 mL/kg of intravenous LR or normal saline (NS). Serum lactate was measured before and after the fluid bolus. The primary outcome was the difference in the change in lactate between the LR and NS groups. Secondarily, we assessed the change in pH, bicarbonate, sodium, and chloride in each group. ResultsAfter 30 mL/kg of intravenous LR, the mean serum lactate level increased by 0.93 mmol/L (95% confidence interval 0.42–1.44 mmol/L). However, there was also a small increase in the mean serum lactate level in the NS group of 0.37 mmol/L (95% confidence interval −0.26 mmol/L to 1.00 mmol/L), such that there was not a statistically significant difference in the change in lactate when comparing the LR group to the NS group (p = 0.2). The NS group saw larger declines in pH and bicarbonate and greater increases in chloride compared with the LR group. ConclusionIn healthy individuals, a modest but significant rise in mean serum lactate was seen after a 30 cc/kg LR bolus. There was no difference in mean serum lactate when comparing a 30 mL/kg bolus of NS to LR.

Outcome of thyroid ultrasound screening in FAP patients with a normal baseline exam.

Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome associated with a substantial lifetime risk for colorectal cancer. The leading extra-colonic causes of cancer in FAP include duodenal and thyroid cancer (TC). Recent guidelines recommend annual thyroid ultrasound (TUS) screening beginning in the teenage years but the evidence to support the interval particularly in FAP patients with a normal baseline ultrasound is lacking. TUS results from FAP patients enrolled in a thyroid screening program from 2006 to 2016 and who had at least 2 TUS were reviewed. TUS findings were classified as normal, low (LR) or high risk (HR) for TC based on nodule characteristics as determined by American Thyroid Association (ATA) guidelines. We assessed the incidence of TC in patient with normal baseline TUS and factors associated with TC. 264 FAP patients were included. Baseline TUS was normal in 167, LR in 74, and HR in 24 patients. Patients were observed for a mean 4.8years and underwent an average of 3 TUS. Patients with normal baseline TUS did not develop TC during the course of follow up of 5.1years. TC developed in 6 patients (2.3%) all with baseline nodules; 5 in the LR group and 1 in the HR group. Factors associated with development of TC were presence of baseline nodule(s) and female sex. The development of TC in FAP patients in a TUS screening program with short term follow up is low and no FAP patient with a normal baseline TUS developed TC during observation. Annual TUS in patients with a normal baseline TUS may not be needed. Extending the screening interval to 2years may be reasonable until nodules are detected.

Efficacy of Lactated Ringer's versus Normal Saline in Treating Patients with Septic Shock

Objective To compare the clinical efficacy of lactated Ringer's (LR) and normal saline (NS) in treating patients with septic shock. Methods The clinical data of 198 patients with septic shock who received fluid resuscitation in the Intensive Care Unit of Quzhou People's Hospital from January 2014 to January 2016 were retrospectively analyzed. These patients were divided into NS group (n=100) and LR group (n=98) according to fluids used. The amounts of trial fluid,other liquids,and blood products and the average total fluid volume were recorded. The oxygenation index (PO2/FiO2),mean artery pressure (MAP),central venous pressure (CVP),and B-type natriuretic peptide (BNP) before and after treatment as well as the early goal-directed therapy (EGDT) 8 h (EGDT8),EGDT 24 h recovery rate,EGDT recovery time,28-day mortality rate were compared. Other secondary outcomes including bleeding,allergic reaction,acute kidney injury (AKI),venous blood filtration (RRT) rate,hyperkalemia,and ICU stay were also recorded. The 28-day survival rate was calculated using the Kaplan-Maier method,and the difference in survival rate was compared by log-rank test. Results The two groups showed no significant difference in gender,age,body weight,source of admission to ICU,procalcitonin level,source of sepsis,Acute Physiology and Chronic Health Evaluation Ⅱ score,number of AKI patients,amount of white blood cells,and C-reactive protein level (all P>0.05). The amount of blood products on the first day [(782±357)ml vs.(606±273)ml;t=2.044,P=0.046] and the average total amount of liquid on the first three days [(5470±1078)ml vs.(5092±929) ml;t=2.640,P=0.009] were significantly higher in NS group than in LR group. The amount of trial fluid and the volumes of other fluids were not significantly different (both P>0.05). The PO2/FiO2,MAP,CVP,and BNP levels significantly increased after treatment in both groups (all P<0.05);however,they were not significantly different between LR group and NS group at different time points before and after treatment (all P>0.05). The incidences of hyperlactacidemia (86.0% vs.71.4%,OR:2.457,95%CI:1.202-5.023,P=0.012) and hyperchloremia (25.0% vs.13.2%,OR:2.179,95%CI:1.041-4.562,P=0.036) were significantly higher in NS group than in LR group. These two groups showed no significant difference in EGDT8,24 h recovery rate,EGDT recovery time,28-day mortality rate,AKI,RRT rate,hyperkalemia,and ICU stay (all P>0.05). Kaplan-Meier survival analysis showed that the 28-day survival rate was not significantly different (χ2 log-rank=0.012,P=0.911). Conclusion When liquid resuscitation is applied in patients with septic shock,the use of LR can lower blood transfusion requirement on the first day and total liquid dosage on the first three days (compared with NR), along with lower incidences of hyperlactacidemia and hyperchloremia,although there was no significant difference in the 28-day mortality rate.

Protective effect of calcium-sensing receptor inhibitor Calhex231 on traumatic hemorrhagic shock rats

Objective To observe the protective effects of calcium-sensing receptor (CaSR) inhibitor Calhex231 on traumatic hemorrhagic shock rats. Methods 144 SD rats were divided into six groups by random number table method: normal group, shock group, lactated Ringer's solution (LR) group, LR+ Calhex231 0.1 mg/kg group, LR+ Calhex231 1 mg/kg group, and LR+ Calhex231 5 mg/kg group, with 16 rats in each group for survival observation and 8 rats for hemodynamics test. 64 SD rats were divided into four groups: normal group, shock group, lactated Ringer's solution (LR) group, LR + Calhex231 1 mg/kg group, with 8 rats in each group for detecting organ blood flow and superior mesenteric artery vascular reactivity and the other 8 rats for mesenteric artery vascular reactivity. After the establishment of traumatic hemorrhagic shock model, the shock group did not receive resuscitation, and the LR group was resuscitated with LR equal to two times of the blood loss volume. The three LR+ Calhex231 groups with different dosages were firstly given LR of equal volume to that of blood loss, and then the Calhex231 was dissolved into LR ( equal to the blood loss volume) to resuscitate. The wound was ligated and sutured immediately after resuscitation. The effect of Calhex231 on animal's 24-hour survival since the beginning of resuscitation was observed. The hemodynamics including the mean arterial blood pressure(MAP), left intraventricular systolic pressure(LVSP), maximal rising, and declining rate of left intraventricular pressure (±dp/dtmax) were observed before shock, at the end of shock, 1 hour after resuscitation, and 2 hours after resuscitation. The effects of Calhex231 on vital organ blood flow and vascular reactivity were observed 2 hours after resuscitation. Results All the shock rats died within 9 hours after the shock model was established. The survival outcomes of LR group rats were slightly improved compared with the shock group rats(P<0.05) . The survival time and 24 hour survival rate of LR+ Calhex231 1 mg/kg group and LR + Calhex231 5 mg/kg group rats were significantly increased compared with the shock group rats (P<0.05). The hemodynamic indexes of LR+ Calhex231 groups were higher than those of the LR group. The best effect was observed in LR + Calhex231 1 mg/kg group rats (P<0.01). The MAP, LVSP and ±dp/dtmax were restored to normal level (64.9%, 82.4%, 89.8%, and 77.8%, respectively). Meanwhile, the blood flow in liver and kidney of LR+ Calhex231 1 mg/kg group rats were increased from 57.2% and 41% to 108.7% and 95.1%, respectively. The vascular reactivity including superior mesenteric artery and mesenteric artery of LR+ Calhex231 1 mg/kg group rats were also increased (P<0.01). Conclusions In rats with hemorrhagic shock, the calcium sensitive receptor inhibitor Calhex231 can improve the vascular reactivity, the hemodynamics, and the blood flow of important organs. It plays a role in protecting the cardiovascular function and reducing the mortality after traumatic hemorrhagic shock. Key words: Receptors, calcium-sensing; Shock, hemorrhagic; Calhex231

Risk-Guided Strategy to Prevent Cytomegalovirus Associated Complications After Liver Transplantation

Aim: We evaluated a risk-guided strategy to prevent cytomegalovirus-associated complications (CMV-ac) after liver transplantation (LT). Patients &amp; methods: Forty liver graft recipients were stratified according to their CMV risk status to prophylactic (high risk, HR and group) or pre-emptive antiviral treatment (intermediate, IR, and low risk, LR and group). A detailed analysis of clinical and virological data was performed. Results: 8/40 patients were classified within the HR, 28/40 within the IR and 4/40 within the LR group. Incidence of CMV viremia was 3/8 (38%) in the HR, 9/28 (32%) in the IR and 0/5 in the LR group. Mortality rate of CMV-ac was 0%. Conclusion: A risk-guided antiviral strategy is effective to prevent severe CMV-ac up to 1 year after LT.

The effect of acetated ringer's solution on inflammatory mediators on lung tissue and their signaling pathways in rats with shock

Objective To study the effects of acetated ringer's solution resuscitation in hemorrhagic shock rats on inflammatory mediators on lung tissue and their JNK (c-Jun N-terminal kinase) signaling pathways. Methods Thirty-two SD rats were randomly(random number) divided into four groups: shock without resuscitation group (CR, n=8), saline group (NR, n=8), lactated ringer's solution group (LR, n=8) and acetated ringer's solution group (AR, n=8). The rats of NR group, LR group and AR group were prepared into shock models (mean arterial blood pressure maintained at 40-45 mmHg), The rats of NR group, LR group and AR group were in the shock for 60 min and then the corresponding kinds of liquid were administered for 30 min and observation was carried out for 4 hours. The rats of CR group without liquid resuscitation were observed for 4 hours after shock. After that, the lung tissues of rats were taken from NR group, LR group and AR group as well as from CR group 4 hours after shock (if the rats died, the lung tissues were immediately taken). The levels of TNF-α, IL-4 and IL-10 mRNA in lung were measured by real-time polymerase chain reaction (RT-PCR) , and Western blot was used to measure the levels of JNK phosphorylation and MKP-1 acetylation. The one-way ANOVA was used for comparison among groups . Between the two groups, the comparison was analyzed by using LSD-t test. Results The IL-4 mRNA expression of lung tissue in AR group was higher than that in CR group, NR group and LR group (CR group:0.42±0.34; NR group:2.60±0.66; LR group:6.24±2.95; AR group:11.08±4.24; P<0.05).The IL-10 mRNA expression of lung tissue in AR group was significantly higher than that in CR group, NR group and LR group (CR group:0.25±0.25; NR group:2.79±1.62; LR group:3.51±1.66; AR group:9.35±2.86; P<0.01).The TNF-α mRNA expression in AR group was significantly lower than that in CR group, NR group and LR group (CR group:4.98±1.26; NR group:2.50±0.76; LR group:3.87±3.00; AR group:0.19±0.09; P<0.01). The level of JNK phosphorylation in lung tissue of rats in AR group was significantly lower than that in CR group, NR group and LR group (CR group:0.52±0.12; NR group:0.42±0.08; LR group:0.30±0.08; AR group:0.17±0.06; P<0.01). The level of MKP-1 acetylation in lung tissue of rats in AR group was significantly higher than that in CR group, NR group and LR group (CR group:0.14±0.07; NR group:0.30±0.07; LR group:0.37±0.02; AR group:0.48±0.06; P<0.01). Compared with normal saline and lactated ringer's solution, acetated ringer's solution used in hemorrhagic shock rats could promote MKP-1 acetylation, inhibit the phosphorylation of JNK, significantly inhibit the lung tissue TNF-α released, promote the release of anti-inflammatory factors, IL-4 and IL-10. Conclusions The acetated ringer's solution for resuscitation of hemorrhagic shock in rats could reduce inflammation of lung tissue in a certain extent, probably by enhanced the acetylation of MKP-1 to inhibited JNK signaling pathway and reduced lung tissue inflammation. Key words: Acetated ringer's solution; Hemorrhagic shock; Rat; Fluid resuscitation; Inflammatory mediators; JNK signaling pathway; lung tissue; MAPK phosphatases-1

2091 Neurophysiological substrates and developmental sequelae of sensory differences in infants at high risk for autism spectrum disorder

OBJECTIVES/SPECIFIC AIMS: Background: Children with autism spectrum disorder (ASD) show a broad range of unusual responses to sensory stimuli and experiences. It has been hypothesized that early differences in sensory responsiveness arise from atypical neural function and produce “cascading effects” on development across a number of domains, impacting social and communication skill, as well as broader development in children affected by ASD. A primary challenge to confirming these hypotheses is that ASD cannot be definitely diagnosed in the earliest stages of development (i.e., infancy). A potential solution is to prospectively follow infants at heightened risk for ASD based on their status as infant siblings of children who are diagnosed. We examined the developmental sequelae and possible neurophysiological substrates of three different patterns of sensory responsiveness—hyporesponsiveness (reduced or absent responding to sensory stimuli) and hyperresponsiveness (exaggerated responding to sensory stimuli), as well as sensory seeking (craving of or fascination with certain sensory experiences). Infants at high risk (HR) for ASD were compared with a control group of infants at relatively lower risk for ASD (LR; siblings of children with typical developmental histories). Objectives: Research questions included: (a) Do HR infants differ from LR infants in early sensory responsiveness?, (b) Does sensory responsiveness predict future ASD and related symptomatology? and (c) Is sensory responsiveness predicted by resting brain states? METHODS/STUDY POPULATION: Methods: To answer these questions, we carried out a longitudinal correlational investigation in which 20 HR infants and 20 LR controls matched on sex and chronological age were followed over 18 months. At entry to the study, when infants were 18 months old, sensory responsiveness was measured using the Sensory Processing Assessment and the Sensory Experiences Questionnaire, and a number of putative neural signatures of early sensory differences were measured via resting state EEG. When infants were 24 and 36 months of age, ASD and related symptomatology was evaluated in a comprehensive diagnostic evaluation. RESULTS/ANTICIPATED RESULTS: Results: HR infants trended towards increased hyporesponsiveness and hyperresponsiveness and showed significantly elevated levels of sensory seeking relative to LR controls at 18 months of age. Both groups, furthermore, displayed a high degree of heterogeneity in sensory responsiveness. Atypical sensory responsiveness (increased hyperresponsiveness and/or hyporesponsiveness, as well as sensory seeking behavior) predicted several aspects of ASD and related symptomatology, including social, communication, and play skill, and was associated with differences in resting brain state, including metrics of oscillatory power, complexity, and connectivity, as well as hemispheric asymmetry. Moderation analyses revealed that several relations varied according to risk group, such that associations were stronger in magnitude in the HR Versus LR group. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: Findings provide empirical support for the notion that early sensory responsiveness may produce cascading effects on development in infants at heightened risk for ASD. Differences in resting brain states may underlie atypical behavioral patterns of sensory responsiveness. From a clinical standpoint, results suggest that early sensory differences may be useful for predicting developmental trajectories, and be potentially important targets for early preventive intervention, in infants at risk for autism.

Comparison of hook plate with versus without double-tunnel coracoclavicular ligament reconstruction for repair of acute acromioclavicular joint dislocations: A prospective randomized controlled clinical trial

PurposeThis study was designed to compare the surgical outcomes of a hook plate with double-tunnel coracoclavicular (CC) ligament reconstruction by conjoined tendon transfer versus single hook plate surgery for the repair of acute type of Rockwood type III and V acromioclavicular (AC) joint dislocations. MethodsThe study cohort included 62 patients with acute (within 6 weeks after trauma) Rockwood type III and V AC joint dislocations who underwent surgery from February 2012 to September 2015. The patients were randomly allocated to the ligament reconstruction group (LR group, n = 31) or the single hook plate group (HP group, n = 31). In both groups, reduction of the AC joint by hook plate and repair of the ruptured AC ligament with absorbable Vicryl sutures were performed homoplastically. The lateral half of the short tendon of the biceps brachii muscle and the lateral half of the flexor tendon were used to reconstruct the trapezoid and conoid ligaments, respectively. Differences in surgical duration, intraoperative blood loss, incision length, and total cost were compared between the two groups. Furthermore, the preoperative and postoperative visual analogue score (VAS), postoperative American Shoulder and Elbow Surgeons (ASES) score, Constant–Murley score (CMS), Karlsson score, complication rates, and patient satisfaction at the last follow-up were compared to evaluate the curative effects of the surgical treatments. Magnetic resonance imaging (MRI) after hook plate removal was used to evaluate the reconstructed ligaments and tendon-bone interface. ResultsIn total, 25 patients in the LR group and 26 in the HP group completed the follow-up. There were no statistically significant differences in age, sex, Rockwood type, placing time, total cost, and follow-up duration between the LR and HP groups (p > 0.05). However, as compared with the HP group, the surgical duration and incision length were longer in the LR group (92.08 ± 19.25 vs. 56.54 ± 21.29 min and 13.64 ± 0.90 vs. 6.65 ± 1.01 cm, respectively, p < 0.05). In addition, there was no significant difference in preoperative VAS scores, but the postoperative VAS score was lower in LR group than in the HP group (2.52 ± 1.19 vs. 4.12 ± 1.45, respectively, p < 0.05). Moreover, patients in LR group had a remarkable higher CMS and ASES score (89.56 ± 2.80 vs. 79.31 ± 4.97 and 92.60 ± 2.79 vs. 82.35 ± 3.44, respectively, p < 0.05). The overall excellent or good result rate, as evaluated by the Karlsson score, was 92.00% (23/25) and 50.00% (13/26), respectively (p < 0.05). MRI findings revealed good condition of the reconstructed ligaments and tendon-bone interface. The incidence of complications was lower and the satisfaction rate was higher in the LR group than in the HP group (1/25 vs. 16/26 and 23/25 vs. 14/26, respectively, p < 0.05). ConclusionsThe overall surgical effect of the use of a hook plate combined with double-tunnel CC ligament reconstruction is superior to single hook plate surgery for the repair of acute Rockwood type III and V AC joint dislocations.

Nutritional risk screening of inpatient children with singer-center gastroenterological diseases in Sichuan province

Objective To evaluate the application of clinical Screening Tool for the Assessment of Malnutrition in Pediatrics(STAMP), and to investigate the nutritional risks of inpatient children with gastroenterological diseases in Sichuan province and their associated clinical characteristics and the features of hygiene economics. Methods STAMP was utilized for nutrition screening of inpatient children with gastroenterological diseases in Chengdu Women and Children′s Central Hospital from January 2015 to March 2017.All the enrolled children were divided into 3 groups accor-ding to the STAMP scores: low risk group (LR group), moderate risk group (MR group) and high risk group (HR group). Clinical and economic data were compared among 3 groups. Results A total of 3 672 assessments were accomplished, including 2 372 times for males and 1 300 times for females( 5 years old: 848 times). Among them, 147 children were identified as LR(4.00%), 2 296 children as MR (62.53%), and 1 229 children as HR (33.47%). Statistically significant differences were observed among 3 groups in average length of hospital stay (P 0.05). Malnutrition rate was 4.08%(6/147 cases) in LR group, 2.05%(47/2 296 cases) in MR group and 31.90%(392/1 229 cases) in HR group, respectively, and among them 146 patients were diagnosed as severe malnutrition.Digestive tract infections were the most common diseases in MR group(66.33%, 1 523/2 296 cases) and HR group(68.27%, 839/1 229 cases). Moreover, children with stomatitis, gastrointestinal postoperation, acute pancreatitis, inflammatory bowel disease, esophageal diseases, digestive malformations, cyclic vomiting, malnutrition, and acute intestinal obstruction were all in HR group. Conclusions Nutritional risk is likely to raise the burden of disease.STAMP is applicabile clinically when it is utilized for nutrition risk screening of inpatient children with gastroenterological diseases in Sichuan province and provides evidence for nutrition support treatment. Key words: Nutrition risk screening; Screening Tool for the Assessment of Malnutrition in Pediatrics; Gas-troenterological disease

Swelling of the Subcutaneous Adipose, but not the Dermis, in Burn Wound Edema is Exacerbated by IV Fluids

Intravenous (IV) resuscitation of burn patients has greatly improved outcomes and become a cornerstone of modern burn care. However, the large volumes of crystalloid given can lead to various comorbidities such as compartment syndromes and acute respiratory distress syndrome. Simultaneously, it is well established that vascular leak leads to significant edema in the severely burned patient. The objective of this study was to begin to examine the interaction of edema of burn wounds and IV fluids. Anesthetized Yorkshire swine sustained 40% total body surface area (TBSA) full‐thickness contact burns with brass probes heated to 100°C placed on the skin for 30 seconds. Animals were recovered from anesthesia and randomized to one of four treatment groups: no IV fluids (n=6), IV lactated Ringer's (LR) resuscitation with the modified Brooke formula (MB; 2 ml/kg/%TBSA, n=6), 15 mL/kg/d of IV LR (LR: n=6), or 15 mL/kg/d fresh frozen plasma (FFP: n=6). Unburned sham animals (n=4) and injured animals were assessed for 48 hours, at which point animals were humanely euthanized and dorsal and ventral dermis was taken to determine wet to dry weight ratios. Additionally, 3 biopsies to include dermis and the entire subcutaneous fat were taken from both the dorsal and ventral aspects of the animal for histological determination of tissue thickness. Burn wound edema was demonstrated by a significantly higher wet:dry ratio in all groups compared to sham animals for dorsal (P=0.017) and ventral (P=0.044) dermis. However, there was no difference amongst the various IV regimens. Moreover, neither burn nor IV fluids induced a difference in the thickness of the dermis on dorsal or ventral locations. In contrast, the thickness of the subcutaneous fat was significantly elevated in both dorsal (P=0.028) and ventral (P=0.0045) samples, depending on IV fluid regimen. Thickness of the dorsal fat layer was 1865 ± 327 μm, 2170 ± 205 μm, 3466 ± 421 μm, 2452 ± 271 μm, and 2707 ± 302 μm for Sham, no IV, MB, LR, and FFP groups, respectively. Thickness of the ventral fat layer was 1557 ± 164 μm, 2728 ± 184 μm, 2618 ± 172 μm, 2368 ± 236 μm, and 3329 ± 352 μm for Sham, no IV, MB, LR, and FFP groups, respectively. Collectively, these data demonstrate that volumes and types of IV fluids can alter burn‐induced edema in an anatomically‐dependent manner. Elucidating the specific drivers of burn wound edema may lead to personalized medicine approaches that can minimize comorbidities associated with over/under resuscitation of the burn patient.Support or Funding InformationThis study was supported by Military Burn Research Program Award# W81XWH‐16‐2‐0041.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intravenous Fluids Used for Resuscitation Alters the Adrenal Response to Traumatic Burn injury Depending on the Volume Given

Severe thermal injury induces hypermetabolic stress which initiates a disruption in the hypothalamic‐pituitary‐adrenal (HPA) axis. While glucocorticoids contribute to maintaining blood pressure in healthy individuals, severely burned patients (i.e., &gt;30% total body surface area; TBSA) have increased circulating cortisol levels that correspond to the extent of injury. However, little is known about adrenal damage following burn injury and the potential effects of common treatments such as intravenous (IV) fluid resuscitation. The objective of this study was to evaluate the effect of IV lactated Ringer's (LR) resuscitation on circulating cortisol, steroidogenic enzymes, and adrenal pathology following burn. Anesthetized Yorkshire swine sustained 40% TBSA burns from brass probes heated to 100 °C and placed on the skin for 30 s. Animals were recovered in metabolic cages to regain consciousness. Burned swine received IV fluid resuscitation with LR at two different volumes: 15 mL/kg body weight (BW)/day (Limited Volume; LV, n=6) or 2 mL/kg/%TBSA/day (Modified Brooke; MB, n=6). Non‐burned animals (Sham) were also Fluid Restricted (S‐FR, n=4) to induce some level of stress. Computerized tomography (CT) scans were performed before and 48 h post‐burn. Blood and urine was collected at baseline (BL), 6, 24, and 48 h following burn, with euthanasia at 48 h for adrenal gland collection. Adrenal histopathology was examined, as well as tissue cytokine levels. Heart and respiratory rate was similar in all animals, while temperature was elevated with burn. Urinary cortisol was elevated following surgery in all animals, however by 24 h S‐FR returned back to BL. Urinary cortisol levels at 48 h levels remained elevated in both MB (13,320±1,760 pg/mg creatinine; p=0.005) and LV (12,230±3,350 pg/mg creatinine; p=0.07) animals when compared with S‐FR (4,040±480 pg/mg creatinine). Similarly, while elevated at baseline, circulating cortisol was higher in the MB group (35449 ± 6878 pg/mL) but not the LR group (16511 ± 6077 pg/mL) compared to S‐FR (20549 ± 3078) at 48 hours. Gene expression of cleavage enzymes (3β‐HSD, CYP17, CYP11, and CYP21) along the cortisol synthesis pathway was not different between burned and S‐FR animals. No changes in CT‐angiography determined volume or Hounsfield units were found. Histologically, adrenal hemorrhaging was found in the cortex of burned animals. Intensity of TUNEL stain on adrenal sections was greatest in LV and MB groups within the cortex (p≤0.05) when compared to S‐FR. Protein levels of IL‐2, IL1ra, IL‐10, and IL‐12 were significantly elevated in LV, but not in MB when compared to S‐FR animals. This study demonstrates that at 48 h after a 40% burn in swine, cortisol remains elevated and adrenal gland integrity is compromised. Data from these studies can help shape resuscitative efforts of burn casualties for potentiating homeostasis of the HPA axis.Support or Funding InformationThis study was supported by Military Burn Research Program Award# W81XWH‐16‐2‐0041.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

T96. A RETROSPECTIVE DATABASE STUDY OF THE RELATIONSHIP BETWEEN ALCOHOL AND CANNABIS USE AND CLINICAL MEASURES IN EARLY PHASE PSYCHOSIS

BackgroundAlcohol is the most commonly abused substance in Canada (18%), with cannabis use being the second most commonly abused substance (7%). People diagnosed with psychotic disorders have similar or increased risk of alcohol and cannabis use disorders compared to the general population. While there is ample data investigating the negative impact cannabis has on the development and course of psychosis, there is very limited data examining the potential role that alcohol might play. This study, therefore, investigates the pattern of alcohol and cannabis use and the clinical impact it might have in those at the early phase of psychotic illness.MethodsThis is a cross-sectional, retrospective, database study of 264 patients at time of admission to the NSEPP (Nova Scotia Early Psychosis Program), in Nova Scotia, Canada. Outcome measures included the following domains: demographics/pattern of use, symptomatology, cognition and function. Four groups of patients with early phase psychosis (EPP) were analyzed according to risk level of current substance use: 1) low risk substance use (LR, n = 44), 2) moderate-high alcohol use only (AU, n = 33), 3) moderate-high cannabis use only (CU, n = 55), and 4) moderate-high combined alcohol and cannabis use (AU+CU, n = 132).ResultsBetween group comparisons revealed statistically significant differences in: age (with the AU group being oldest), gender (with LR and AU groups with higher % females compared to CU and CU+AU groups), Positive psychotic symptoms (with AU group having the least positive symptoms), anxiety (with AU group having most anxiety symptoms), and functioning (with AU group having higher social/occupational functioning scores).DiscussionOur findings reveal significant between group differences in a group of 264 patients at time of entry into the NSEPP. The age differences may suggest that those who develop psychosis at an older age could be more predisposed to use alcohol primarily. Alternatively, it is possible that alcohol somehow delays the onset of psychosis. The gender differences suggest that females with EPP use cannabis less commonly, and seem to choose alcohol use only if they are substance users. There are less intense positive psychotic symptoms (as measured by the positive and negative syndrome scale, PANSS) and more intense trait anxiety symptoms (measured by the state trait anxiety inventory, STAI) in the AU group which may either indicate that anxiety is worsened and positive symptoms are somehow suppressed with alcohol use, or else might reflect a subgroup in the EPP population (with less positive symptoms and more anxiety symptoms) that self-select for alcohol use. Finally, the AU group have the highest social/occupational functioning (measured with the social and occupational functioning assessment scale, SOFAS), which may indicate that alcohol facilitates social interaction/functioning; however based on existing literature, this finding more likely represents the fact that the more social someone is, the more likely they are to be exposed to alcohol in their peer group, and are therefore more likely to drink alcohol.

Lactated Ringer' Solution may be Superior to Saline-Based 6% Hydroxyethyl Starch 130/0.4 for Early Resuscitation within 12 hours from Hemorrhagic Shock

ABSTRACTPurpose: To compare the effects of fluid resuscitation with lactated Ringer's solution (LR) and saline-based 6% hydroxyethyl starch 130/0.4 (HES) on the inflammatory response and oxidative stress in the small intestine as well as on bacterial translocation to the liver. Methods: Sprague–Dawley rats were subjected to blood pressure-controlled hemorrhagic shock and then resuscitated with LR or HES. At 1, 3, 6, 12, and 24 hr after resuscitation, liver tissues were collected to count the bacterial colonies, and small intestines were harvested to analyze the levels of inflammatory (TNF-α and HO-1) and oxidative stress (MPO) mediators as well as the intestinal injury by immunohistochemistry, colorimetry and hematoxylin & eosin staining, respectively. Results: The expression level of TNF-α in the LR group was stable from 1 to 6 hr but decreased at 12 hr and then abruptly increased at 24 hr. The expression level of TNF-α in the LR group was significantly lower than that in the HES group, especially during the first 12 hr post-fluid infusion. MPO activity decreased to its lowest level at 3 hr but increased from 6 to 12 hr, with no difference at 24 hr between the two groups. Although a decreasing tendency was observed from 6 hr, HO-1 expression levels remained higher in the LR group than in the HES group at 12 and 24 hr, particularly at 12 hr. During the initial 12 hr, the LR group exhibited significantly lower colony-forming units in the liver tissues than the HES group. Chiu's score in the intestine decreased regardless of which resuscitative fluids were used. Conclusions: During early resuscitation (within 12 hr), LR may be superior to HES in reducing intestinal injuries by suppressing inflammatory and oxidative mediators.

Effect of different concentrations of hypertonic sodium fluid resuscitation on intestine injury in rats at the early stage of severe burn

To investigate the effect of different concentrations of hypertonic saline solution (HS) on intestine injury in rats at the early stage of severe burn. 104 adult healthy female Sprague-Dawley (SD) rats were randomly divided into five groups: sham group (n = 8), lactated Ringer solution (LR) group (n = 24) and 200, 300, 400 mmol/L HS group (HS200 group, HS300 group, HS400 group, all n = 24). All the rats in LR group and different concentrations of HS groups were scalded for 30% total body surface area (TBSA) with III degree, after immediately, the rats were given burn resuscitation therapy by LR or corresponding concentrations of HS through the tail vein. Eight rats were sacrificed on the 2nd, 8th and 24th post-injury hour (PIH), respectively, to collect abdominal aorta blood and intestinal tissues. The rats in sham group were given simulation of burns without resuscitation, which were immediately sacrificed and the specimens were harvested. The serum Na+ concentration was determined by automatic biochemical analyzer. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) contents in serum were determined by enzyme-linked immunosorbent assay (ELISA). The moisture content of intestine reflected by intestine wet/dry weight (W/D) ratio was determined. The content of malondialdehyde (MDA) and the activity of diamine oxidase (DAO) in intestinal tissue were determined by ultraviolet spectrophotometer. The activation of von Willebrand factor (vWF) was assessed by using immunohistochemistry. Compared with sham group, and the contents of TNF-α and IL-1β in blood and W/D ratio and MDA contents in intestine at each time point after injury in LR group and three HS groups were significantly increased, and the activity of intestinal DAO was significantly decreased. The serum Na+ concentration was significantly reduced in the LR group as compared with that in the sham group, which was significantly higher in the three HS groups than that in the sham group, with the most obvious change on the 8th PIH. Compared with LR group, the serum Na+ concentration and the activity of intestine DAO at each time point after injury in different concentrations of HS groups were significantly increased, and the serum contents of TNF-α, IL-1β and the W/D ratio, MDA contents in intestine were significantly lowered showing a dose dependent. The changes of HS400 group was the most significantly, and the difference on the 8th PIH was statistically significant as compared with LR group [blood Na+ (mmol/L): 145.51±0.72 vs. 131.52±0.85, intestinal DAO (U/g): 4.85±0.30 vs. 3.50±0.45, blood TNF-α (ng/L): 88.47±4.91 vs. 153.21±13.45, blood IL-1β (ng/L): 85.77±3.42 vs. 140.57±10.46, intestinal W/D ratio: 3.32±0.05 vs. 3.73±0.09, intestinal MDA (nmol/mg): 0.58±0.01 vs. 0.82±0.04, all P < 0.05]. The immunohistochemical results showed that the vWF activity in the LR group and different concentrations of HS groups was significantly reduced as compared with that of the sham group. Compared with LR group, the activity of intestinal vWF at each time point in different concentration of HS groups was increased to some extent with a dose dependent. The positive staining in HS400 group was the deepest, which showed that the activity of intestinal vWF was the strongest after treated by 400 mmol/L HS. Compared with LR, HS can attenuate intestinal tissue injury of rats at the early stage of severely burned, and of all, the curative effect of 400 mmol/L HS is the best.