Predicting factors for major trauma patient mortality analyzed from trauma registry system.

OBJECTIVE: We investigated the predictors of mortality in major trauma patients using a trauma registry system database. METHODS: Data were obtained from the trauma registry of a level I trauma center for all patients aged ≥18 years admitted to an intensive care unit (ICU) between January 1, 2006 and December 31, 2013. Models were adjusted for patient demographics, injury mechanism, preexisting comorbidity, Glasgow coma scale (GCS), injury severity score (ISS), emergency department (ED) and ICU procedures, surgical procedures, and complications. Multivariate logistic regression analysis was used to determine predictors of mortality and odds ratios of its associated factors. RESULTS: In total, 1561 patients met the inclusion criteria. The overall mortality rate was 13.4%. After controlling for all variables in a logistic regression model, the factors associated with increased mortality risk (P < 0.05) were age ≥ 45 years; ISS > 24; GCS score < 8 and 8-12; fall accident; preexisting comorbidity of renal insufficiency; ED cardiopulmonary resuscitation (CPR) procedures; ICU blood transfusion; and cardiovascular, respiratory, digestive system and infection complications. CONCLUSION: Our data showed some predictors of patient mortality after major trauma, most of which were determined during the trauma event. Only those treatment complications may be improved when performing the treatment procedures.

Role of gender in the survival outcome of acute phase of major trauma: A nationwide, population-based study.

BACKGROUND: Animal models of trauma have shown that females have better posttraumatic survival; however, results of previous studies on the influence of gender on major trauma patients have been controversial. This study aimed to evaluate the association between gender and survival in major trauma patients. METHODS: We retrospectively analyzed patients registered in Taiwan's National Health Insurance Research Database between 2008 and 2012 with the diagnosis codes 800-939 and 950-957 (International Classification of Diseases, ninth revision, clinical modification). Data on gender, age, catastrophic illness, and new injury severity score (NISS) ≥16 were collected for comparing patients' mortality after trauma. Propensity score matching (PSM) was performed to eliminate dissimilarities in age, comorbidities, NISS, and primary traumatic regions between the genders. RESULTS: Among 10 012 major trauma patients included in the study cohort, 28.8% (n = 2880) were women. The PSM patient group consisted of 50% (2876 of 5752) women. Women had a higher 30-day (15.4% of women vs 13.8% of men; p < 0.05) and hospital (16.1% of women vs 14.5% of men; p < 0.05) mortality and lower incidence rates of acute respiratory dysfunction (62.5% of women vs 65.9% of men; p < 0.005) and acute hepatic dysfunction (0.8% of women vs 2.1% of men; p < 0.001). However, the analysis of PSM patient groups showed lower mortality rates in women with moderate trauma (NISS 16-24) in the acute phase within three days (1.4% of women vs 2.7% of men, p = 0.03). Analysis of patients with an NISS of 16-24 who died within three days showed a higher NISS in women than in men (19.7 ± 2.3 vs 18.0 ±1.9, respectively, p <0.05). CONCLUSION: There is no gender difference in 30-day or hospital mortality among major trauma patients. However, women admitted for moderate major trauma had higher survival within three days of major trauma.

N-acetylcysteine and atorvastatin alleviates lung injury due to ischemia-reperfusion injury in rats.

BACKGROUND: Acute lung injury is a major cause of death following severe injury and ischemia-reperfusion (IR). We investigated the protective effect of pretreatment with N-acetylcysteine (NAC) and atorvastatin (ATOR) in a mesenteric IR rat model. METHODS: Male rats were randomly divided into five experimental groups: sham; mesenteric IR; and ATOR, NAC, ATOR + NAC (A + N) pretreatment followed by IR. Blood gas and cytokine levels, biochemistry, and cell count were analyzed. Lung injury was evaluated through histopathology and by using the wet-to-dry lung weight (W/D) ratio. RESULTS: Following IR, significant changes were noted in biochemistry, cytokine, and lung injury. Compared with those in the IR group, neutrophil-to-lymphocyte ratio, lactate and alanine aminotransferase (ALT) levels were lower in all pretreatment groups, and creatinine and alkaline phosphatase (ALKP) levels were lower only in the A + N group. Blood pH and base excess (BE) were higher, and partial pressure of carbon dioxide in venous blood (PvCO2) lowered significantly in the ATOR and A + N groups than those in the IR group, and bicarbonate (HCO3-) levels increased only in the A + N group. Lung injury scores and W/D indicated significant attenuation in the A + N group. Compared with those in the IR group, tissue tumor necrosis factor-α levels were significantly lower in all the pretreatment groups and interleukin-1ß levels were lower in the A + N group. CONCLUSION: NAC and ATOR decreased inflammation and lung injury following mesenteric IR in rats. NAC and ATOR may alleviate lung injury more efficiently in combination than individually.

Impact of Age-Adjusted Charlson Comorbidity on Hospital Survival and Short-Term Outcome of Patients with Extracorporeal Cardiopulmonary Resuscitation.

Extracorporeal cardiopulmonary resuscitation (ECPR) has gradually come to be regarded as an effective therapy, but the hospital mortality rate after ECPR is still high and unpredictable. The present study tested whether age-adjusted Charlson comorbidity index (ACCI) can be used as an objective selection criterion to ensure the most efficient utilization of medical resources. Adult patients (age ≥ 18 years) receiving ECPR at our institution between 2006 and 2015 were included. Data regarding ECPR events and ACCI characteristics were collected immediately after the extracorporeal membrane oxygenation (ECMO) setup. Adverse events during hospitalization were also prospectively collected. The primary endpoint was survival to hospital discharge. The second endpoint was the short-term (2-year) follow-up outcome. A total of 461 patients included in the study were grouped into low ACCI (ACCI 0⁻3) (240, 52.1%) and high ACCI (ACCI 4⁻13) (221, 47.9%) groups. The median ACCI was 2 (interquartile range (IQR): 1⁻3) and 5 (IQR: 4⁻7) for the low and high ACCI groups, respectively. Cardiopulmonary resuscitation (CPR)-to-ECMO duration was comparable between the groups (42.1 ± 25.6 and 41.3 ± 20.7 min in the low and high ACCI groups, respectively; p = 0.754). Regarding the hospital survival rate, 256 patients (55.5%) died on ECMO support. A total of 205 patients (44.5%) were successfully weaned off ECMO, but only 138 patients (29.9%) survived to hospital discharge (32.1% and 27.6% in low and high ACCI group, p = 0.291). Multivariate logistic regression analysis revealed CPR duration before ECMO run (CPR-to-ECMO duration) and a CPR cause of septic shock to be significant risk factors for hospital survival after ECPR (p = 0.043 and 0.014, respectively), whereas age and ACCI were not (p = 0.334 and 0.164, respectively). The 2-year survival rate after hospital discharge for the 138 hospital survivors was 96% and 74% in the low and high ACCI groups, respectively (p = 0.002). High ACCI before ECPR does not predict a poor outcome of hospital survival. Therefore, ECPR should not be rejected solely due to high ACCI. However, high ACCI in hospital survivors is associated with a higher 2-year mortality rate than low ACCI, and patients with high ACCI should be closely followed up.

The Benefit of Ultrasound in Deciding Between Tube Thoracostomy and Observative Management in Hemothorax Resulting from Blunt Chest Trauma.

BACKGROUND: Hemothorax is most commonly resulted from a closed chest trauma, while a tube thoracostomy (TT) is usually the first procedure attempted to treat it. However, TT may lead to unexpected results and complications in some cases. The advantage of thoracic ultrasound (TUS) over a physical examination combined with chest radiograph (CXR) for diagnosing hemothorax1 has been proposed previously. However, its benefits in terms of avoiding non-therapeutic TT have not yet been confirmed. Therefore, this study is aimed to evaluate the severity of hemothorax in blunt chest trauma patients by using TUS in order to avoid non-therapeutic TT in stable cases. METHODS: The data from 46,036 consecutive patient visits to our trauma center over a four-year period were collected, and those with blunt chest trauma were identified. Patients who met any of the following criteria were excluded: transferred from another facility, with an abbreviated injury scale (AIS) score ≥ 2 for any region except the chest region, with a documented finding of tension pneumothorax or pneumothorax >10%, younger than 16 years old and with indications requiring any non-thoracic major operation. The decision to perform TT for those patients in the non-TUS group was made on the basis of CXR findings and clinical symptoms. The continuous data were analyzed by using the two-tailed Student's t test, and the discrete data were analyzed by Chi-square test. RESULTS: A total of 84 patients met the criteria for inclusion in the final analysis, with TT having been performed on 42 (50%) of those patients. The mean volume of the drainage amount was 860 ml after TT. The TT drainage was less than 500 ml in 12 patients in the non-TUS group (40%), while none was less than 500 ml in the TUS group (p = 0.036, Fisher's exact test). In terms of the positive rate of subsequent effective TT, the sensitivity of TUS was 90% and the specificity was 100%. There were 3 patients with delayed hemothorax: 2 of the 58 (3.6%) in the non-TUS group and 1 of 26 (4.5%) in the TUS group (p > 0.05, Fisher's exact test). The hospital length of stay in the non-TUS group with non-therapeutic TT was significantly longer than in the TUS group without TT (8.2 vs. 5.4 days, p = 0.018). There were no other major complications or deaths in either group during the 90-day follow-up period. CONCLUSION: In the case of blunt trauma, TUS can rapidly and accurately evaluate hemothorax to avoid TT in patients who may not benefit much from it. As a result, the rate of non-therapeutic TT can be decreased, and the influence on shortening hospital length of stay may be further evaluated with prospective controlled study.

The impact of open to collaborative care model in cardiovascular surgical unit.

BACKGROUND: When compared with open care model, a closed one improves patient care in intensive care units (ICUs), mixed ICUs, surgical ICUs and trauma centers. We wanted to evaluate the benefit of a collaborative care model in highly specialized cardiovascular care unit. METHODS: This study was a retrospective, observational study conducted in the cardiovascular care unit of a teaching hospital. All patients who were above 20 years old and had received cardiovascular operation were enrolled for data collection and analysis. RESULTS: A total of 270 subjects were enrolled for analysis during the 2-year study period. In the collaborative care model, the CVSU length of stay (p = 0.001) and CVSU-free days (p = 0.0008) were significantly better than those in an open care model. DISCUSSION: The collaborative care model improved postoperative outcome in the cardiovascular surgical unit for those needing prolonged ICU care.

Increased flow resistance and decreased flow rate in patients with acute respiratory distress syndrome: The role of autonomic nervous modulation.

BACKGROUND: The aim of this study was to investigate the flow resistance and flow rate in patients with acute respiratory distress syndrome (ARDS) in the surgical intensive care unit and their relation with autonomic nervous modulation. METHODS: Postoperative patients of lung or esophageal cancer surgery without ARDS were included as the control group (n = 11). Patients who developed ARDS after lung or esophageal cancer surgery were included as the ARDS group (n = 21). The ARDS patients were further divided into survivor and nonsurvivor subgroups according to their outcomes. All patients required intubation and mechanical ventilation. RESULTS: The flow rate was significantly decreased, while the flow resistance was significantly increased, in ARDS patients. The flow rate correlated significantly and negatively with positive end-expiratory pressure (PEEP), while the flow resistance correlated significantly and positively with PEEP in ARDS patients. Furthermore, the flow rate correlated significantly and negatively with the tidal volume-corrected normalized high-frequency power but correlated significantly and positively with the tidal volume-corrected low-/high-frequency power ratio. In contrast, the flow resistance correlated significantly and negatively with normalized very low-frequency power and tidal volume-corrected low-/high-frequency power ratio, but correlated significantly and positively with tidal volume-corrected normalized high-frequency power. CONCLUSION: The flow rate is decreased and the flow resistance increased in patients with ARDS. PEEP is one of the causes of increased flow resistance and decreased flow rate in patients with ARDS. Another cause of decreased flow rate and increased flow resistance in ARDS patients is the increased vagal activity and decreased sympathetic activity. The monitoring of flow rate and flow resistance during mechanical ventilation might be useful for the proper management of ARDS patients.

Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion.

BACKGROUND: Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cell-based therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model. METHODS: C57BL/6 mice were randomly divided into the following groups: sham/no treatment, vehicle treatment with phosphate-buffered saline, treatment with iPSCs, and treatment with iPSC-conditioned medium. The mice were subjected to mesenteric ischemia for 45 minutes followed by reperfusion for 24 hours. After I/R, the lungs and the ileum of the mice were harvested. Lung injury was evaluated by histology, immunohistochemistry, and analyses of the levels of inflammatory cytokines, cleaved caspase 3, and 4-hydroxynonenal. RESULTS: The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered saline-treated group, the iPSC-treated group displayed a decreased intensity of acute lung injury 24 hours after mesenteric I/R. iPSC transplantation significantly reduced the expression of proinflammatory cytokines, oxidative stress markers, and apoptotic factors in injured lung tissue and remarkably enhanced endogenous alveolar cell proliferation. iPSC-conditioned medium treatment exerted a partial effect compared with iPSC treatment. CONCLUSION: When considering the anti-inflammatory, antioxidant, and antiapoptotic properties of iPSCs, the transplantation of iPSCs may represent an effective treatment option for mesenteric I/R-induced acute lung injury.

Appendectomy timing: Will delayed surgery increase the complications?

BACKGROUND: This study investigated whether the time from emergency room registration to appendectomy (ETA) would affect the incidence of perforation and postoperative complications in patients with acute appendicitis. METHODS: Patients who underwent an appendectomy at the Ren-Ai branch of Taipei City Hospital between January 2010 and October 2012 were retrospectively reviewed. Their demographics, white blood cell count, C-reactive protein, body temperature, computed tomography scan usage, operation method, pathology report, postoperative complication, length of hospital stay, and ETA were abstracted. Multivariate analysis was performed to search the predictors, including ETA, of outcomes for the perforation and postoperative complication rates. RESULTS: A total of 236 patients were included in the study. Perforation occurred in 12.7% (30/236) and postoperative complications developed in 24.1% (57/236) of these patients. There were 121 patients with ETA <8 hours, 88 patients with ETA of 8-24 hours, and 27 patients with ETA >24 hours; patients with ETA >24 hours had significantly longer hospital stay. Univariate analysis showed that perforated patients were significantly older, and had higher C-reactive protein level, longer hospital stay, and higher complication rate. Patients who developed postoperative complications were significantly older, and had higher neutrophil count, less use of computed tomography, and higher open appendectomy rate. After multivariate analysis, age ≥55 years was the only predictor for perforation [odds ratio (OR) = 3.65; 95% confidence interval (CI), 1.54-8.68]; for postoperative complications, age ≥55 years (OR = 1.65; 95% CI, 1.84-3.25), perforated appendicitis (OR = 3.17; 95% CI, 1.28-7.85), and open appendectomy (OR = 3.21; 95% CI, 1.36-7.58) were associated. ETA was not a significant predictor in both analyses. CONCLUSION: In our study, it was observed that although longer ETA was associated with longer hospitalization, ETA was not correlated with postoperative complications. Our results inclined toward the position that appendectomy can be performed as a semielective surgery.

Expression profile of MicroRNAs in gram-negative bacterial sepsis.

Bacterial lipopolysaccharide (LPS) is an effective trigger of the inflammatory response during infection with gram-negative bacilli (GNB), which implicates the pathogenesis of sepsis and septic shock. MicroRNAs (miRNAs) are shown to have a significant role in the fine-tuning of toll-like receptor (TLR)-mediated inflammatory response. We profiled miRNA expression levels in peripheral leukocytes of GNB urosepsis patients and compared them with those of healthy controls. We further explored the regulatory mechanism of endotoxin-responsive miRNAs in TLR and cytokine signaling by using human monocytic cell line (THP-1 cells) treated with LPS antigen stimulation. The expression of two miRNAs, that is, let-7a (P < 0.001) and miR-150 (P < 0.001), were confirmed to be significantly downregulated in GNB urosepsis patients compared with healthy controls. The expression of let-7a is first to be identified as a biomarker of GNB sepsis. By using an in vitro model with the human monocytic cell line, we demonstrated that LPS stimulation downregulated the THP-1 cell expression of let-7a. The downregulation of let-7a is correlated with the induced expression of cytokine-inducible Src homology 2-containing protein without change in cytokine-inducible Src homology 2-containing protein mRNA levels in THP-1 cells via TLR signaling pathway activation. Moreover, gain of function by overexpression of let-7a revealed that let-7a significantly decreased tumor necrosis factor-α and interleukin-1ß production in response to LPS. Reduced let-7a and miR-150 levels in peripheral leukocytes correlate with GNB urosepsis patients. Furthermore, let-7a is relevant to the regulation of TLR-mediated innate immune response.

Induced pluripotent stem cells mediate the release of interferon gamma-induced protein 10 and alleviate bleomycin-induced lung inflammation and fibrosis.

Chronic lung diseases cause serious morbidity and mortality, and effective treatments are limited. Induced pluripotent stem cells (iPSCs) lacking the reprogramming factor c-Myc (3-gene iPSCs) can be used as ideal tools for cell-based therapy because of their low level of tumorigenicity. In this study, we investigated whether 3-gene iPSC transplantation could rescue bleomycin-induced pulmonary fibrosis. After the induction of pulmonary inflammation and fibrosis via intratracheal delivery of bleomycin sulfate, mice were i.v. injected with 3-gene iPSCs or conditioned medium (iPSC-CM) at 24 h after bleomycin treatment. Administration of either 3-gene iPSCs or iPSC-CM significantly attenuated collagen content and myeloperoxidase activity, diminished neutrophil accumulation, and rescued pulmonary function and recipient survival after bleomycin treatment. Notably, both treatments reduced the levels of inflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-2, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein 1 yet increased the production of the antifibrotic chemokine interferon-γ-induced protein 10 (IP-10) in bleomycin-injured lungs. Furthermore, IP-10 neutralization via treatment with IP-10-neutralizing antibodies ameliorated the reparative effect of either 3-gene iPSCs or iPSC-CM on collagen content, neutrophil and monocyte accumulation, pulmonary fibrosis, and recipient survival. Intravenous delivery of 3-gene iPSCs/iPSC-CM alleviated the severity of histopathologic and physiologic impairment in bleomycin-induced lung fibrosis. The protective mechanism was partially mediated by the early moderation of inflammation, reduced levels of cytokines and chemokines that mediate inflammation and fibrosis, and an increased production of antifibrotic IP-10 in the injured lungs.

Drug abuse-related accidents leading to emergency department visits at two medical centers.

BACKGROUND: Drug abuse is becoming more prevalent in Taiwan, as evidenced by increasing reports of drug trafficking and drug abuse-related criminal activity, and the wide use of more contemporary illicit drugs. Consequently, drug abuse-related accidents are also expected to occur with greater frequency. However, no study has yet specifically evaluated the prevalence, pattern, and outcomes of drug abuse-related accidents among patients visiting emergency departments (EDs) in Taiwan. METHODS: We conducted an ambidirectional study with patients who visited the EDs of Taipei Veterans General Hospital (TVGH) and China Medical University Hospital (CMUH) due to drug abuse-related accidents from January 2007 through September 2009. Information on the patients' baseline characteristics and clinical outcomes was collected and analyzed. RESULTS: During the study period, a total of 166 patients visited the EDs of one of the two study hospitals due to drug abuse-related accidents. This yielded a prevalence of drug abuse of 0.1% among all patients visiting the ED due to accident and/or trauma. Fifty-six out of the 166 patients visited the ED at TVGH, most patients being between 21 and 40 years old. Opioids (41.1%) were the drugs most commonly abused by the patients, followed by benzodiazepines (32.1%). More than two-thirds of the patients (n=38, 67.9%) required hospitalization, and three patients died (5.4%). In contrast, 110 patients with drug abuse-related accidents visited the ED at CMUH during the study period. Most of these subjects had abused benzodiazepines (69.1%), were between 21 and 40 years old, and were female. Fewer than one-fifth of the patients (n=19, 17.3%) required hospitalization, with no deaths reported. There were significant between-hospital differences in terms of patient gender, drugs of choice, injury mechanisms, method and time of the ED visit, triage levels, and need for hospitalization. CONCLUSION: Although the prevalence of drug abuse-related accidents was low, and only three patient deaths were reported in this study, many patients presented to the EDs with severe effects and later required hospitalization. Better and timely management of such patients will help to minimize the adverse health impacts associated with drug abuse. Governmental agencies and all healthcare professionals should also work together to fight against the surging trend of drug abuse in Taiwan.

Predictive indications of operation and mortality following renal trauma.

BACKGROUND: This study is a review of our experiences related to managing patients with renal injuries and identifying the predictive indicators of surgery and mortality. METHODS: A retrospective review study was performed in our university hospital. Patients with renal injuries were enrolled. Data comparisons were performed between four patient groups (operation vs. nonoperation groups and mortality vs. survival groups, respectively). RESULTS: Seventy-three patients were enrolled in this study, 55 of whom (75.34%) were male. Nine patients (12.33%) were severely injured (Injury severity score (ISS) ≥ 16), and nine (12.33%) had high renal injury scores (Renal injury scale (RIS) ≥ 4). Seven patients (9.59%) had received operations, and four (5.48%) died of hemorrhagic shock and multiple organ failure. After performing multivariate analysis, patients who received operations had significantly higher ISS (≥16) and RIS (≥4) scores compared with patients who did not undergo operations. ISS ≥ 16 and Glasgow coma scale (GCS) < 8 were significantly correlated with mortality. CONCLUSION: In conclusion, ISS ≥ 16 and RIS ≥ 4 are predictive factors for necessitating an operation, and higher injury severity (ISS ≥ 16) and lower consciousness level (GCS < 8) scores are significantly associated with mortality after renal trauma.

Relation of signal in mononuclear cell with endotoxin response and clinical outcome after trauma.

BACKGROUND: We investigated the correlation of proinflammatory transcript nuclear factor κB (NF-κB) and antioxidative gene transcript nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in peripheral blood mononuclear cells (PBMCs) with the tumor necrosis factor α (TNF-α) response after endotoxin stimulation and the clinical outcome of severely injured patients. METHODS: Thirty-two severe blunt trauma patients (injury severity score>16) with systemic inflammatory response syndrome were enrolled. Age- and sex-matched healthy persons were the controls. Patients' blood samples were obtained at 24 and 72 hours after injury. Peripheral blood mononuclear cells were isolated, and measurements for NF-κB p65 translocation, Nrf2 and phosphorylated inhibitory κB-α expressions, and TNF-α levels were assayed after endotoxin stimulation. RESULTS: In the trauma patients, TNF-α hyporesponse, depressed NF-κB p65 translocation, and phosphorylated inhibitory κB-α expression in PBMCs were found at 24 and 72 hours after injury; the Nrf2 expressions in PBMCs were not significantly different between patients and controls. The TNF-α levels had significant correlation with the NF-κB translocation and the trend of negative correlation with Nrf2 expression. Fifteen patients had critical injury (injury severity score≥25). Patients with critical injury had a lower NF-κB signal and a lower TNF-α response than did the counter group. Twelve patients developed organ failure; their Nrf2 expressions were significantly lower than those of patients without organ failure. CONCLUSIONS: The endotoxin hyporesponse associated with NF-κB and Nrf2 signal alternations in PBMCs of injured patients develops early after injury. The hyporesponse of PBMCs with a lower TNF-α level correlates with a lower NF-κB signal and is associated with critical injury, whereas a depressed Nrf2 expression in PBMCs is associated with later organ failure in trauma patients.

Magnolol attenuates the lung injury in hypertonic saline treatment from mesenteric ischemia reperfusion through diminishing iNOS.

BACKGROUND: Hypertonic saline (HTS) administration can decrease the inflammation following ischemia reperfusion. Magnolol is a potent antioxidant. The present study investigated whether combined treatment of magnolol and HTS could provide further protection in mesenteric ischemia reperfusion injury. METHODS: Male C3H/HeOuJ mice were randomly segregated into the following groups: sham-operated (sham), vehicle treatment and mesenteric ischemia reperfusion (MSIR) (vehicle-treated), magnolol treatment and MSIR (magnolol-treated), HTS treatment and MSIR (HTS-treated), as well as co-administration of magnolol plus HTS and MSIR (combined-treated). In MSIR, mice were subjected to mesenteric ischemia for 60 min followed by reperfusion for 30 min. Lung injury was evaluated by lung edema (water ratio) and myeloperoxide (MPO) activity; RNA expression of inducible nitric oxide synthetase (iNOS), TNF-α, and IL-6 were assayed by real time RT-PCR. The formation of peroxynitrite in plasma was assayed by the peroxynitrite-dependent oxidation of dihydrorhodamine 123 (DHR 123) to rhodamine. RESULTS: Compared with those in the sham-treated group, lung edema and MPO activity, expressions of iNOS, TNF-α and IL-6, and plasma peroxynitrite were significantly increased in the vehicle-treated group. Significant attenuations of these parameters were found in the magnolol-treated or HTS-treated animals. Combined treatment of magnolol and HTS further suppressed the lung edema, iNOS, and TNF-α expressions, and plasma peroxynitrite, compared with the results of a single treatment of magnolol or HTS. CONCLUSIONS: Compared with single-agent use, co-administration of magnolol and HTS further decreases iNOS expression and plasma peroxynitrite as well as the degree of lung injury from MISR. These results may provide another treatment measure for post-injury immunomodulation.

IV delivery of induced pluripotent stem cells attenuates endotoxin-induced acute lung injury in mice.

BACKGROUND: Induced pluripotent stem (iPS) cells are novel stem cell populations, but the role of iPS cells in acute lung injury (ALI) is not currently known. We investigated the effect of iPS cells in modifying the pathophysiology of endotoxin-induced ALI. METHODS: Male C57BL/6 8- to 12-week-old mice were enrolled in this study. Mouse iPS cells were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathologic findings, the pulmonary levels of cytokines, and functional parameters were analyzed after either 24 h or 48 h. RESULTS: More iPS cells integrated into the lungs of mice with ALI than those of the control mice, as demonstrated by in vivo radionuclide imaging and in vitro Hoechst-labeled fluorescent staining. iPS cells significantly diminished the histopathologic changes of ALI and the lung injury score. There was also a significant reduction in the activity of nuclear factor-κB (NF-κB) and neutrophil accumulation in the lung, confirmed by immunostaining, electrophoretic mobility shift assays, and the decrease of myeloperoxidase activity, in the iPS-cell-treated mice with ALI. These protective effects were not replicated by the control cell therapy with fibroblasts. iPS cells mediated a downregulation of the proinflammatory response to endotoxin (reducing tumor necrosis factor-α, IL-6, and macrophage inflammatory peptide-2). In addition, iPS cells rescued the hypoxemia and pulmonary function of ALI. Treatment with a conditioned medium of iPS cells showed effects similar to those of iPS cells, which may suggest the therapeutic benefits of iPS mediated by paracrine factors. CONCLUSIONS: IV delivery of iPS cells provides a beneficial effect to attenuate the severity of endotoxin-induced ALI and improve physiologic impairment, which is partly mediated by a reduction in NF-κB activity and neutrophils accumulation. The conditioned medium of iPS cells demonstrated effects equal to those of iPS cells.

Spleen artery embolization increases the success of nonoperative management following blunt splenic injury.

BACKGROUND: Spleen artery embolization (SAE) may increase the success rate of nonoperative management (NOM). The present study investigated the clinical outcome after the installation of SAE in the management of blunt splenic injury. METHODS: A retrospective review of hospital records was performed to enroll patients with blunt injury of the spleen. Demographic data and information about the injury severity score, organ injury scale, hospitalization days, management and final outcomes were evaluated. Patients were separated into early and late groups according to the year that SAE was selectively used (2003-2004 and 2005-2008). RESULTS: Six of eleven (55%) patients in the early group were successfully managed without surgery for blunt splenic injury, whereas all of the 38 patients (100%) in the late group were successfully managed without surgery. Eleven patients (11 of 38; 28.9%) received SAE in the late group. The rate of NOM increased from 55% in the early group to 100% in the late group (p < 0.001). Both early and late groups had similar injury severity score, length of hospitalization, blood transfusion, and complications, and there was no mortality. CONCLUSION: Performance of SAE for the patients with blunt splenic injury could increase the successful rate of NOM significantly and safely. An algorithm including the angioembolization might be beneficial in the management of patients with blunt spleen trauma.

Randomized, double blind, placebo-controlled trial of fish-oil-based lipid emulsion infusion for treatment of critically ill patients with severe sepsis.

OBJECTIVE: The present study aimed to determine the clinical benefits to critically ill patients with severe sepsis of receiving parenteral fish-oil-based lipid emulsion as adjuvant treatment. METHODS: This was a prospective, randomized, double-blind, placebo-controlled clinical trial of 28 patients with severe sepsis in the intensive care unit of a primary and referral teaching hospital. RESULTS: Fourteen patients were randomly assigned to the study group and a similar number were placed in the control group. The study group showed a significant score reduction for Acute Physiology and Chronic Health Evaluation (APACHE) II on day 3 (p = 0.004), day 5 (p = 0.032) and day 7 (p = 0.03), together with APACHE III (p = 0.028) and Simplified Acute Physiology Score II (p = 0.019) on day 7. The serum procalcitonin level was significantly decreased in the study group on day 3 (p = 0.018), day 5 (p = 0.011) and day 7 (p = 0.028). However, the serum tumour necrosis factor-α level, length of intensive care unit and hospital stay showed no significant difference when the groups were compared. CONCLUSION: Adjuvant treatment with fish-oil-based lipid emulsion of 10% Omegaven for critically ill patients with severe sepsis is probably safe and helpful for rapid reduction of clinical severity of the disease.

Severe bleeding after antithrombotic therapy in urosepsis masquerading as myocardial infarction.

Cardiac dysfunction is common in patients with severe sepsis and septic shock. We present a 71-year-old woman with Escherichia coli urosepsis and sepsis-induced myocardial injury masquerading as non-ST elevated myocardial ischemia. Spontaneous psoas hematoma requiring blood transfusion and intracranial hemorrhage developed after antiplatelet and anticoagulant therapies, even in therapeutic doses. The patient was managed conservatively and recovered well with minor residual hemiparesis. Bleeding complications are a common risk of antithrombotic therapy. It is therefore crucial to weigh the impact of efficacy against safety. Old age, female gender, renal insufficiency and sepsis character increased the risk of bleeding in this patient. A misinterpretation of elevated cardiac troponin I may give rise to a diagnostic dilemma and cause unnecessary morbidity.