Shao-Chun Wu

Profiling Circulating MicroRNA Expression in Experimental Sepsis Using Cecal Ligation and Puncture

The levels of circulating microRNAs (miRNAs) in mice with experimental sepsis induced by cecal ligation and puncture (CLP) were determined using whole blood samples obtained from C57BL/6 mice at 4, 8, and 24 h after CLP; miRNA expression analysis was performed in these samples using an miRNA array. Microarray analysis revealed upregulation of 10 miRNA targets (miR-16, miR-17, miR-20a, miR-20b, miR-26a, miR-26b, miR-106a, miR-106b, miR-195, and miR-451). The expression of these miRNA targets in the whole blood, serum, and white blood cells (WBCs) of CLP mice was quantified using quantitative real-time PCR; these values were compared to those in sham-operated C57BL/6 mice, and the results indicated that these miRNA targets were significantly up-regulated in the whole blood and serum but not in the WBCs. In addition, the levels of these 10 miRNA targets in the serum of Tlr2−/−, Tlr4−/−, and NF-κB−/− mice at 8 h after CLP did not decrease significantly., which indicated that the transcription of these miRNAs was not directly mediated by the TLR2/NF-κB or TLR4/NF-κB pathway, and pathways induced by exposure to the gram-positive or gram-negative bacteria. Immunoprecipitation with the Argonaute 2 ribonucleoprotein complex revealed significantly increased expression of the 10 miRNA targets in the serum of mice after CLP, and the levels of 6 (miR-16, miR-17, miR-20a, miR-20b, miR-26a, and miR-26b) of these 10 miRNA targets increased significantly in exosomes isolated using ExoQuick precipitation solution. In this study, we identified circulating miRNAs that were up-regulated after CLP and determined the increase in the levels of these miRNAs, and our results suggest that circulating Ago2 complexes and exosomes may be responsible for the stability of miRNAs in the serum.

Weight-reduction through a low-fat diet causes differential expression of circulating microRNAs in obese C57BL/6 mice

BackgroundTo examine the circulating microRNA (miRNA) expression profile in a mouse model of diet-induced obesity (DIO) with subsequent weight reduction achieved via low-fat diet (LFD) feeding.ResultsEighteen C57BL/6NCrl male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal %) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal % high-fat diet (HFD) for 12 weeks; and (3) DIO + LFD, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal % LFD for 4 weeks. A switch to LFD feeding led to decreases in body weight, adiposity, and blood glucose levels in DIO mice. Microarray analysis of miRNA using The Mouse & Rat miRNA OneArray® v4 system revealed significant alterations in the expression of miRNAs in DIO and DIO + LFD mice. Notably, 23 circulating miRNAs (mmu-miR-16, mmu-let-7i, mmu-miR-26a, mmu-miR-17, mmu-miR-107, mmu-miR-195, mmu-miR-20a, mmu-miR-25, mmu-miR-15b, mmu-miR-15a, mmu-let-7b, mmu-let-7a, mmu-let-7c, mmu-miR-103, mmu-let-7f, mmu-miR-106a, mmu-miR-106b, mmu-miR-93, mmu-miR-23b, mmu-miR-21, mmu-miR-30b, mmu-miR-221, and mmu-miR-19b) were significantly downregulated in DIO mice but upregulated in DIO + LFD mice. Target prediction and function annotation of associated genes revealed that these genes were predominantly involved in metabolic, insulin signaling, and adipocytokine signaling pathways that directly link the pathophysiological changes associated with obesity and weight reduction.ConclusionsThese results imply that obesity-related reductions in the expression of circulating miRNAs could be reversed through changes in metabolism associated with weight reduction achieved through LFD feeding.

Geriatric hospitalizations in fall-related injuries.

BackgroundTo investigate the injury pattern, severity, and mortality of elderly patients hospitalized for treatment of trauma following fall accidents.MethodsData obtained from the Trauma Registry System were retrospectively reviewed for trauma admissions between January 1, 2009 and December 31, 2013 in a Level I trauma center. Of 16,548 registered patients, detailed information was retrieved from the 2,403 elderly patients (aged 65 years and above) with fall accidents and was compared with information from 1,909 adult patients (aged 20–64) with fall accidents.ResultsFalls presented the major mechanism for admission (59.9%) in the elderly patients. The number of elderly patients who fell from a height <1 m was greater than that of the adult patients (91.9% vs. 62.5%, respectively, p <0.001). The Injury Severity Score (ISS) (9.3 ± 4.4 vs. 8.3 ± 6.1, respectively, p =0.007) and New Injury Severity Score (NISS) (10.3 ± 6.8 vs. 9.5 ± 8.2, respectively, p <0.001) were significantly higher in the elderly than the adult patients. A significantly larger proportion of the elderly patients were admitted to the ICU (16.2% vs. 13.4%, respectively, p =0.009), and the elderly were found to have longer stays in the intensive care unit (ICU) (8.6 days vs. 7.6 days, respectively, p =0.034) but not in the hospital in general (9.6 days vs. 8.5 days, respectively, p =0.183). Additionally, a significantly higher percentage of the elderly patients sustained subdural hematoma (10.1% vs. 8.2%, respectively, p =0.032) and femoral fracture (50.6% vs. 14.1%, respectively, p <0.001). There were significant differences in in-hospital mortality (18.2% vs. 10.3%, respectively, p =0.031) and length of stay in the hospital (11.6 days vs. 14.9 days, respectively, p =0.037) between the elderly and adult patients with subdural hematoma, but not between those with femoral fracture.ConclusionsAnalysis of the data indicates that elderly patients hospitalized for treatment of trauma following fall accidents present with a bodily injury pattern that differs from that of adult patients and have a higher severe injury score, worse outcome, and higher mortality than those of adult patients.

Target-controlled infusion vs. manually controlled infusion of propofol with alfentanil for bidirectional endoscopy: a randomized controlled trial

BACKGROUND AND STUDY AIMS The best anesthesia methods for analgesia and sedation during gastrointestinal endoscopy are still debated. The aim of this study was to compare the recovery time, clinical presentations, and satisfaction between target-controlled infusion (TCI) and manually controlled infusion (MCI) in same-day bidirectional endoscopy (esophagogastroduodenoscopy followed by colonoscopy). PATIENTS AND METHODS A total of 220 patients with American Society of Anesthesiology physical status 1 or 2 were enrolled and randomized into the TCI or MCI groups. The clinical presentations, vasoactive drug demand, propofol consumption, and adverse events were recorded for both groups peri-procedurally. The concentrations of propofol in the plasma (Cp) and at the site of drug effect (Ce) by computerized simulation were also monitored in both groups. Finally, the satisfaction of patients, endoscopists, and nurse anesthetists was assessed by questionnaire after the examinations. RESULTS Compared with the MCI group, the TCI group had a faster recovery time (17.91 ± 7.72 minutes vs. 14.58 ± 8.55 minutes; P = 0.002), less moderate hypotension (7.37 ± 15.46 % vs. 1.82 ± 5.15 %; P < 0.001), and shorter period of bradypnea (13.81 ± 15.92 % vs. 9.18 ± 12.00 %; P = 0.013). In addition, the TCI group reduced the relative risk of moderate desaturation by 50 % compared with the MCI group (30.9 % vs. 15.5 %; 95 % confidence interval 1.191-3.360; P = 0.007). CONCLUSIONS The study demonstrated that TCI of propofol combined with alfentanil was associated with a faster recovery time, and better hemodynamic and respiratory stability than MCI in same-day bidirectional endoscopy. CLINICAL TRIAL REGISTRATION CGMH IRB Identifier 97-0969B.

Pain Management of Living Liver Donors With Morphine With or Without Ketorolac

BACKGROUND To compare the efficacy and dose requirements for intravenous (IV) patient-controlled analgesia (PCA) with morphine only versus morphine with ketorolac for living liver donors after partial hepatectomy. PATIENTS AND METHODS Eighty living liver donors who had undergone partial hepatectomy received 3 days of IV PCA for postoperative pain control. Some were prescribed a PCA with morphine alone (group I) or morphine with ketorolac (group II), while both had a rescue dose of IV fentanyl (25 μg). The daily consumption of morphine, pain score, and frequency of rescue fentanyl doses were compared retrospectively using the Mann-Whitney U test and the incidence of side effects with chi-square tests; a P value of .05 was regarded as significant. All the data are shown as mean values±standard deviations. RESULTS The 80 subjects were distributed as 57 group I and in 23 group II patients. The daily consumption of morphine, Visual Analogue Scale (VAS) and side effects were not different between the groups, but group II required significantly fewer rescue doses to achieve pain relief. CONCLUSION Both regimens provided acceptable pain control with daily VAS less than 3. The use of ketorolac in the PCA did not reduce the daily total morphine requirements with a similar incidence of side effects but a significantly reduced requirement for rescue doses, which subsequently reduced the work load of personnel in the pain control service.

Predictive factors associated with re-exploration for hemostasis in living donor liver transplantation.

BACKGROUND After liver transplantation (LT), re-exploration of the abdomen to check for bleeding is sometime required. Our study aimed to identify the predictive factors by analysis of preoperative and intraoperative presentations that may impact the re-exploration for hemostasis. MATERIAL/METHODS We selected 522 consecutive recipients from the Liver Transplant Program database and medical records between January 1, 1994 and December 1, 2009 in our hospital. Demographic data (age, sex, body mass index, weight, MELD score), preoperative laboratory tests (Hb, platelet, albumin, bilirubin, INR, APTT), and intraoperative presentations (ascites and blood loss, crystalloids, 5% albumin infused, blood products used (such as LPRBC, RBC, FFP, platelet, cryoprecipitate), urine output, Hb at end of operation, and anesthesia) were collected for primary comparison. Potential predictors found by univariate comparison at p<0.1 were put into a multiple binary logistic regression model. RESULTS Thirty-eight (7.3%) recipients required re-exploration for hemostasis after LDLT; 80% needed re-exploration only once. In univariate analysis, recipients transfused with FFP >10 ml/kg had a 4.2-fold increased risk of re-exploration (p<0.001). Thirteen potential predictors by univariate comparison at p<0.1 were selected into a multiple binary logistic regression. Fresh frozen plasma (FFP) transfused was the sole predictor. CONCLUSIONS Each elevation of 1ml of transfused FFP per kg is associated with a 1.033-fold increased incidence of re-exploration for hemostasis. Patients transfused with more than 10 ml/kg FFP during LT require more intensive management within 72 hours due to increase risk of postoperative bleeding.

Prediction of Massive Transfusion in Trauma Patients with Shock Index, Modified Shock Index, and Age Shock Index

Objectives: The shock index (SI) and its derivations, the modified shock index (MSI) and the age shock index (Age SI), have been used to identify trauma patients with unstable hemodynamic status. The aim of this study was to evaluate their use in predicting the requirement for massive transfusion (MT) in trauma patients upon arrival at the hospital. Participants: A patient receiving transfusion of 10 or more units of packed red blood cells or whole blood within 24 h of arrival at the emergency department was defined as having received MT. Detailed data of 2490 patients hospitalized for trauma between 1 January 2009, and 31 December 2014, who had received blood transfusion within 24 h of arrival at the emergency department, were retrieved from the Trauma Registry System of a level I regional trauma center. These included 99 patients who received MT and 2391 patients who did not. Patients with incomplete registration data were excluded from the study. The two-sided Fisher exact test or Pearson chi-square test were used to compare categorical data. The unpaired Student t-test was used to analyze normally distributed continuous data, and the Mann-Whitney U-test was used to compare non-normally distributed data. Parameters including systolic blood pressure (SBP), heart rate (HR), hemoglobin level (Hb), base deficit (BD), SI, MSI, and Age SI that could provide cut-off points for predicting the patients’ probability of receiving MT were identified by the development of specific receiver operating characteristic (ROC) curves. High accuracy was defined as an area under the curve (AUC) of more than 0.9, moderate accuracy was defined as an AUC between 0.9 and 0.7, and low accuracy was defined as an AUC less than 0.7. Results: In addition to a significantly higher Injury Severity Score (ISS) and worse outcome, the patients requiring MT presented with a significantly higher HR and lower SBP, Hb, and BD, as well as significantly increased SI, MSI, and Age SI. Among these, only four parameters (SBP, BD, SI, and MSI) had a discriminating power of moderate accuracy (AUC > 0.7) as would be expected. A SI of 0.95 and a MSI of 1.15 were identified as the cut-off points for predicting the requirement of MT, with an AUC of 0.760 (sensitivity: 0.563 and specificity: 0.876) and 0.756 (sensitivity: 0.615 and specificity: 0.823), respectively. However, in the groups of patients with comorbidities such as hypertension, diabetes mellitus, or coronary artery disease, the discriminating power of these three indices in predicting the requirement of MT was compromised. Conclusions: This study reveals that the SI is moderately accurate in predicting the need for MT. However, this predictive power may be compromised in patients with HTN, DM or CAD. Moreover, the more complex calculations of MSI and Age SI failed to provide better discriminating power than the SI.

Intraoperative blood and fluid administration differences in primary liver transplantation versus liver retransplantation.

OBJECTIVES Liver retransplantation (Re-LT) is the effective therapy for irreversible liver graft failure after primary liver transplantation (LT). The challenges faced by the operative team in the Re-LT setting have been seldom elucidated. Our aim is to analyze the differences in fluid management in primary LT and Re-LT during the surgical procedure. METHODS The anesthesia charts of 16 patients who underwent both primary LT and Re-LT at our center in the space from October 1995 to May 2009 were analyzed. Group 1 (GI) consisted of patients who underwent primary LT, whereas patients in Group 2 (GII) were patients in GI but underwent Re-LT. GI was further divided into two subgroups depending on whether they had previous abdominal surgery before primary LT (GIB) or not (GIA). Wilcoxon signed-ranks test was used to compare GI and GII, and GIA and GIB. A p value less than 0.05 was regarded as significant. Data were given as mean ± standard deviation. RESULTS Blood loss was significantly increased from 48.9 ± 106 mL/kg in GI to 251.5 ± 242 mL/kg in GII. Consequently more blood products, crystalloids, sodium bicarbonate, calcium chloride, and neosynephrine were required to support the hemodynamics in GII. In GI, GIB tended to bleed more and required more blood transfusions than GIA. CONCLUSION More bleeding is expected in Re-LT than primary LT. Additional anesthetic personnel, more intravenous lines, and blood and blood products should be readily available to deal with the emergent fluid and hemodynamic resuscitations in anesthesia for Re-LT.

Use of Spectral Entropy Monitoring in Reducing the Quantity of Sevoflurane as Sole Inhalational Anesthetic and in Decreasing the Need for Antihypertensive Drugs in Total Knee Replacement Surgery

BACKGROUND The use of spectral entropy for monitoring the depth of anesthesia or level of hypnosis in surgery or painful procedures can reduce the consumption of drugs and shorten the recovery time of total intravenous anesthesia such as by propofol. The aim of this study was to investigate: (1) the consumption of sevoflurane as the sole anesthetic; and (2) hemodynamic stability in orthopedic surgery with tourniquet inflation under the guidance of spectral entropy, in contrast with the conventional method. METHODS Sixty-five patients, ASA I or II, scheduled to undergo total knee replacement were enrolled and randomized into an entropy-guided group or a conventionally-monitored group. In the conventional group, the depth of anesthesia was judged by the clinical experience of the anesthesia provider based on the hemodynamic response. In the entropy group, state entropy (SE) and response entropy (RE) were kept within the range of 35-45 and an adequate gradient of 5-10 intraoperatively. The overall consumption of sevoflurane (mL) was monitored by the GE Datex-Ohemda S/5 Anesthetic Delivery Unit System. The physiologic changes during five major events in sequence in total knee replacement surgery, i.e., intubation, tourniquet inflation, skin incision, deflation and extubation, were observed closely over the first 5 minutes after each individual event. Within the first 5 minutes of each event, antihypertensive drugs were prohibited. The rest of the time, changes were recorded at 5-minute intervals and the use of rescue medication was allowed in case of need. We compared the heart rate, mean arterial pressure, SE, RE, sevoflurane concentration and rescue drugs in both groups. RESULTS The sevoflurane consumption was significantly lower in the entropy group than in the conventional group (27.79 +/- 7.4 mL vs. 31.42 +/- 6.9 mL; p < 0.05). During the first 5 minutes of each major event, there were no significant differences in hemodynamics between the two groups. In the ensuing time, entropy-guided anesthesia was associated with significantly less frequent need of antihypertensive drugs (0.94 vs. 1.48 times; p = 0.043), especially in the 45-60 minutes after tourniquet inflation (p = 0.012). CONCLUSION Using spectral entropy monitoring for guiding the depth of sevoflurane anesthesia in total knee replacement surgery can reduce its consumption and the frequency of use of antihypertensive drugs.

Bicycle-related hospitalizations at a Taiwanese level I Trauma Center

BackgroundThis study aimed to investigate differences in injury severity and mortality between patients who met with bicycle or motorcycle accidents and were hospitalized at a Level I trauma center in Taiwan.MethodsWe performed a retrospective analysis of bicycle-related injuries that have been reported in the Trauma Registry System in order to identify and compare 699 bicyclists to 7,300 motorcyclists who were hospitalized for treatment between January 1, 2009 and December 31, 2013. Statistical analyses of the injury severity, associated complications, and length of stay in the hospital and intensive care unit (ICU) were performed to compare the risk of injury of bicyclists to that of motorcyclists with the corresponding unadjusted odds ratios and 95 % confidence intervals (CIs). Adjusted odds ratios (AORs) and 95 % CIs for mortality were calculated by controlling for confounding variables that included age, and an Injury Severity Score (ISS) was calculated.ResultsMore of the cyclists were under 19 years of age or over 70 than were the motorcyclists. In contrast, fewer bicyclists than motorcyclists wore helmets, arrived at the emergency department between 11 p.m. and 7 a.m., and had a positive blood alcohol concentration test. The bicyclists sustained significantly higher rates of injuries to the extremities, while motorcyclists sustained significantly higher rates of injuries to the head and neck, face, and thorax. Compared to motorcyclists, the bicyclists had significantly lower ISSs and New Injury Severity Scores, shorter length hospital stays, and a smaller proportion of admittance into the ICU. However, the bicyclists had higher AORs for in-hospital mortality (AOR: 1.2, 95 % CI: 1.16–1.20). In terms of critical injury severity (ISS ≥ 25), the bicyclists had 4.4 times (95 % CI: 1.95–9.82) the odds of mortality than motorcyclists with the same ISSs.ConclusionsData analysis indicated that the bicyclists had unique injury characteristics including bodily injury patterns and lower ISSs, but had higher in-hospital mortality compared to motorcycle riders. In this study, given that only 9 % of bicyclists reported wearing helmets and considering the high mortality associated with head injury, it is possible that some bicycle riders underestimated the gravity of cycling accidents.