LPS priming-induced immune tolerance mitigates LPS-stimulated microglial activation and social avoidance behaviors in mice.

In this study, we investigated the regulatory mechanisms underlying the effects of LPS tolerance on the inflammatory homeostasis of immune cells. LPS priming-induced immune tolerance downregulated cyclooxygenase-2, and lowered the production of prostaglandin-E2 in microglial cells. In addition, LPS tolerance downregulated the expression of suppressor of cytokine signaling 3, and inducible nitric oxide synthase/nitric oxide; suppressed the LPS-mediated induction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1; and reduced reactive oxygen species production in microglial cells. LPS stimulation increased the levels of the adaptive response-related proteins heme oxygenase-1 and superoxide dismutase 2, and the levels of heme oxygenase-1 (HO-1) enhanced after LPS priming. Systemic administration of low-dose LPS (0.5 mg/kg) to mice for 4 consecutive days attenuated high-dose LPS (5 mg/kg)-induced inflammatory response, microglial activation, and proinflammatory cytokine expression. Moreover, repeated exposure to low-dose LPS suppressed the recruitment of peripheral monocytes or macrophages to brain regions and downregulated the expression of proinflammatory cytokines. Notably, LPS-induced social avoidance behaviors in mice were mitigated by immune tolerance. In conclusion, immune tolerance may reduce proinflammatory cytokine expression and reactive oxygen species production. Our findings provide insights into the effects of endotoxin tolerance on innate immune cells and social behaviors.

Value of monocyte distribution width for predicting severe cholecystitis: a retrospective cohort study.

OBJECTIVES: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity. METHODS: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade. RESULTS: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay. CONCLUSIONS: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early.

Lipid-Free Parenteral Nutrition Is Associated with an Increased Risk of Hepatic Dysfunction in Surgical Critically Ill Patients: A Retrospective Observational Study.

To evaluate the effects of lipid-free parenteral nutrition (PN) and various intravenous fat emulsions (IVFEs) on hepatic function in surgical critically ill trauma/acute care surgery patients. We retrospectively reviewed trauma/acute care surgery patients without admission hepatic disorder that received PN. The PN groups include lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish-oil contained PN. We excluded patients with (1) age <18 years, (2) without surgery, (3) preexisting liver injury/diseases, (4) hyperbilirubinemia at admission, (5) received more than one type of PN, and (6) repeated ICU episodes in the same hospitalization. Hepatic dysfunction was considered as serum total-bilirubin >6.0 mg/dL. The demographics, severity score, comorbidities, blood stream infection, and mortality were collected for analyses. The major outcome is hepatic function. We also performed analyses stratified by separated lipid doses (g/kg/day). A total of 249 patients were enrolled. There were no demographic differences among groups. The lipid-free PN group had a higher incidence of hepatic dysfunction and mortality. Compared to the lipid-free group, the other three IVFEs had significantly lower risks of hepatic dysfunction, while the olive oil-based group had a significantly lower risk of 30 and 90-day mortality. After being stratified by separating lipid doses, the soybean oils showed a decreasing trend of hepatic dysfunction and mortality with increased dosage. Fish oil >0.05 g/kg/day was associated with lower hepatic dysfunction incidences. Our findings suggest that, when compared to IVFEs, surgical critically ill patients with trauma/acute care surgery that received lipid-free PN are associated with an increased risk of hepatic dysfunction. In addition, the olive oil-based group had a significantly lower risk of mortality, while fish oil >0.05 g/kg/day was associated with lower incidences of hepatic dysfunction; however, further studies are warranted.

Lipid-Free PN is Associated with an Increased Risk of Hyperbilirubinemia in Surgical Critically Ill Patients with Admission Hepatic Disorder: A Retrospective Observational Study.

BACKGROUND: To evaluate the effect of different PN types on surgical critically ill trauma/acute care surgery patients with hepatic disorders at admission. METHODS: This is a retrospective study. The PN types included lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish oil-containing PNs. Patients admitted with liver injury or liver surgery, elevated serum AST/ALT level, and elevated serum total bilirubin level were included. The exclusion criteria are as follows: 1) age <18 years, 2) severe liver disease/cirrhosis, 3) received more than one type of PN and 4) serum total bilirubin >4.9 mg/dl at admission. Demographics, severity, comorbidities, blood stream infection, hyperbilirubinemia (total bilirubin > 6.0 mg/dl), and mortality were collected for analysis. We also performed analysis stratified by separated lipid doses (g/kg/day). RESULTS: A total of 156 patients were enrolled. There were no demographic differences among groups. The lipid-free group was associated with the highest mortality rate and incidence of hyperbilirubinemia. Compared to the lipid-free group, the olive oil-based group had the lowest risk of hyperbilirubinemia. After being stratified by separated lipid doses, the incidence of hyperbilirubinemia decreased when the lipid dosage increased. Regarding different types of lipids, patients who received more than the median dosage of lipids showed a significantly lower risk of hyperbilirubinemia, except in the fish oil-containing group. CONCLUSION: Our result suggested that lipid-free PN is associated with an increased risk of hyperbilirubinemia in surgical critically ill patients with admission hepatic disorder. Further studies are warranted.

Decreased risk of liver and intrahepatic cancer in non-H. pylori-infected perforated peptic ulcer patients with truncal vagotomy: a nationwide study.

The vagal nervous system is central to the physiological responses and systemic diseases of the liver. We evaluated the subsequent risk of liver and intrahepatic cancer (HCC/ICC) in non-H. pylori (HP)-infected perforated peptic ulcer (PPU) patients with and without vagotomy. Hospitalized PPU patients who underwent simple closure or truncal vagotomy/pyloroplasty (TVP) in the National Health Insurance Research Database from 2000 to 2008 were enrolled. The exclusion criteria included: (1) Multiple surgeries for PPU were received at the same admission; (2) Any cancer history; (3) Previous peptic ulcer-associated surgery; (4) HP infection history; (5) Viral hepatitis infection history; (6) Follow-up duration < 1 year; and (7) Age < 18 years. The risks of developing HCC/ICC in PPU patients with and without vagotomy were assessed at the end of 2013. To balance the baseline condition between groups, we used the propensity score matched method to select study subjects. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence interval (CI) of HCC/ICC. Before propensity score matching, 675 simple suture patients and 54 TVP patients had HCC/ICC, which corresponded to incidences of 2.11 and 0.88 per 1000 person-years, respectively. After propensity score matching, 145 simple suture patients and 54 TVP patients experienced HCC/ICC, which corresponded to incidences of 1.45 and 0.88 per 1000 person-years, respectively. The TVP patients had a 0.71 (95% CI 0.54-0.95)- and 0.69 (95% CI 0.49-0.97)-fold risk of developing HCC/ICC compared to simple suture patients before and after propensity score matching. Our findings reported that, in the Asian population, TVP decreases the risk of HCC/ICC in non-HP-infected PPU patients compared to simple closure patients. However, further studies are warranted.

SUMO E3 ligase PIAS1 is a potential biomarker indicating stress susceptibility.

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS. Local overexpression of PIAS1 in the hippocampus followed by CSDS exposure promoted stress resilience by attenuating social avoidance and improving anxiety-like behaviors. Viral-mediated gene transfer to generate a conditional knockdown of PIAS1 in the hippocampus promoted social avoidance and stress vulnerability after subthreshold microdefeat. HS mice displayed decreased levels of glucocorticoid receptor (GR) expression, and GR SUMOylation in the hippocampus was associated with stress vulnerability. Furthermore, cytokine/chemokine levels were changed predominantly in the hippocampus of HS mice. These results suggest that hippocampal PIAS1 plays a role in the regulation of stress susceptibility by post-translational modification of GRs.

A comparative study of risk of pneumonia and mortalities between nasogastric and jejunostomy feeding routes in surgical critically ill patients with perforated peptic ulcer.

INTRODUCTION: Enteral nutrition (EN) is important in the management of critically illness. Yet, the best route (e.g. pre-pyloric or post-pyloric) for EN in critically ill patients remains to be investigated, especially in specific surgical patients group. In addition, EN could be associated with a higher risk of aspiration pneumonia. Therefore, we evaluate the effect of various EN routes in surgical critically ill perforated peptic ulcer (PPU) patients who underwent surgery and required mechanical ventilation. METHOD: We collected data of surgical critically ill PPU patients admitted to intensive care unit. The patients were managed with appropriate care bundle and program. To reduce the impact of surgery types, we excluded those who had received other surgical procedures and included patients that only received simple closure. Patients were classified into nasogastric and jejunostomy feeding groups. The demographics, severity scores (e.g.: APACHE II, SOFA, and POSSUM), body mass index (BMI), comorbidities, ventilator days, use of proton pump inhibitors (PPIs), pneumonia occurrence, mortality and complications were collected for analysis. RESULTS: A total of 136 critically ill PPU patients that received surgery and mechanical ventilation were enrolled. There were 53 patients in NG group and 83 patients in FJ group. There were no differences in demographics, severity scores, BMI, comorbidities, ventilator days, use of PPIs, pneumonia occurrence, mortalities and complications between groups. CONCLUSION: Our study indicates that there are no differences in mortalities and pneumonia occurrence using nasogastric or feeding jejunostomy in surgical critically ill PPU patients underwent surgery. However, further studies are required.

Use of extracorporeal membrane oxygenation in severe traumatic lung injury with respiratory failure.

OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) in managing acute respiratory distress syndrome had been accepted. Severe lung injury with respiratory failure is often encountered in trauma patients. We report our experience with the use of ECMO in severe traumatic lung injury. METHODS: Patients with severe traumatic lung injury that met the following criteria were candidates for ECMO: (1) severe hypoxemia, Pao2/fraction of inspired oxygen (1.0) less than 60, and positive end-expiratory pressure greater than 10 cm H2O in spite of vigorous ventilation strategy; (2) irreversible CO2 retention with unstable hemodynamics; and (3) an initial arterial Pao2/fraction of inspired oxygen (1.0) less than 60, where the pulmonary condition and hemodynamics rapidly deteriorated despite vigorous mechanical ventilation strategy. RESULTS: Over 60 months, a total of 19 patients with severe traumatic lung injury who received ECMO management were retrospectively reviewed. The median age was 38 years (25-58 years), the median injury severity score was 29 (25-34), the median admission Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 25 (21-36), and the median blood transfusion volume was 5500 mL (3500-13 000). There were 9 venovenous and 10 venoarterial types. The survival rate was 68.4% (13/19). The survivors were younger (30 vs 53 years; 21-39 vs 48-63). There were 6 mortalities (3 pneumonia, 2 coagulopathy, and 1 cardiac rupture with cardiac tamponade). There were 5 of 19 patients with pre-ECMO traumatic brain hemorrhage (3 survived and 2 mortalities). A total of 16 patients received heparinization with 5 mortalities. CONCLUSIONS: The use of ECMO may offer an additional treatment modality in severe traumatic lung injury with respiratory failure that is unresponsive to optimal conventional ventilator support. Timely ECMO intervention is of value.

Laparoscopic appendectomy versus open appendectomy in pregnancy: a population-based analysis of maternal outcome.

BACKGROUND: Laparoscopic appendectomy (LA) is the standard treatment of acute appendicitis for the general population; however, there is still some doubt regarding its safety for pregnant patients. Therefore, the purpose of this study is to investigate and compare the maternal outcome of pregnant patients with acute appendicitis following either an open appendectomy (OA) or LA from a population-based database. METHODS: This study is based on the National Health Insurance Research Database. Patients with both ICD-9-CM codes for appendicitis (540.9, 540.0, and 540.1) and pregnancy (V22) in the same admission were considered to have acute appendicitis during pregnancy. These patients were divided into three groups according to the type of treatment: LA, OA, and non-operative treatment. Outcome measures that were compared between the groups included maternal complications such as preterm labor, abortion, and the need of cesarean section. Besides, the differences of medical expenditure and length of hospital stay between the groups were also analyzed. RESULTS: From 2005 to 2010, a total of 859 pregnant women who had acute appendicitis were identified. They had increased risks for preterm labor, abortion, and increased requirement of cesarean section compared to the control group (i.e., those without acute appendicitis). Among the three groups, the non-operated group has the highest risk of preterm labor. Patients who underwent LA did not have any increased risk of maternal complications compared to the OA group. Furthermore, LA patients had shorter hospital stay than OA. CONCLUSION: Compared to non-operative treatment, appendectomy is the preferred treatment for pregnant patients who have acute appendicitis. LA can be performed safely in pregnant patients without bringing additional maternal complications compared to OA.

Early predictors for tissue healing deficit and leakage in geriatric critically ill patients receiving emergent abdominal surgery: a case control study.

BACKGROUND: As our world ages and the elderly population grows. Surgery on the aged critically ill tend to result in additional morbidity and mortality. We sought to determine early predicting factors that were associated with postoperative leakage and tissue healing deficiency after emergent abdominal surgery in geriatric critically ill patients. MATERIAL AND METHOD: Retrospectively, geriatric critically ill patients received anticipated, single-stage emergent abdominal surgery via emergency room were enrolled. Patients who received only one definitive surgery during their hospital course were labeled as group A, patients received anticipated one-stage surgery and eventually with postoperative leakage and tissue healing deficiency were labeled as group B. The demographics and parameters were obtained for comparison. RESULT: There were 45 patients in group A, and 34 patients in group B. The mean age is 77.4 ± 6.1 years in Group A and 76.9 ± 8.5 years in Group B, the mean APACHE score was 20.3 ± 7.5 vs. 21.6 ± 7.7. There were no significances in age, gender, comorbidities, and physiological scores. There were significances in the persistent post-operative use of vasopressors and hypoalbuminemia. The 30-day mortality rate was 0% in group A and 38.2% in group B. CONCLUSION: Persistent post operative vasopressor use and hypoalbuminemia are associated with higher rate of morbidity and mortality after emergent abdominal surgery in geriatric critically ill patients. Early recognition is essential for proper management. Further studies are required for a better understanding in identifying risk factors.

Trauma during pregnancy: a population-based analysis of maternal outcome.

BACKGROUND: Serious injury during pregnancy is known to cause adverse maternal outcomes. However, the significance of minor injuries in adverse maternal outcomes requires clarification because most injuries sustained during pregnancy are minor ones. METHODS: Two population-based databases (inpatient and ambulatory care) were used to identify pregnant women who had severe (required hospitalization) or minor injuries (required ambulatory care only) prenatally. ICD-9-CM coding was used to categorize the types of prenatal injury and complications during delivery. The patient demographics, types and timing of the injuries, and their association with adverse maternal outcomes were compared among the uninjured, those with minor injury, and those with severe injury. Odds ratios were calculated to estimate the risks of having adverse outcomes in injured pregnant women compared with those who are uninjured. RESULTS: The severely injured women tended to be younger (<20 years old), lived in less urbanized regions, and had lower income levels than those who were uninjured or had minor injury. Motor vehicle crash was the most common mechanism of injury. While minor injuries were associated with preterm labor [odds ratio (OR)=1.25], a severe injury was strongly associated with increased risks of preterm labor, placental abruption, uterine rupture, and maternal death, especially during the third trimester (OR=2.71, 6.12, 7.79, and 20.15, respectively). Injuries away from the trunk could also lead to adverse maternal outcomes. CONCLUSIONS: Trauma during pregnancy, whether minor or severe, is associated with unfavorable maternal outcomes. Injuries considered minor for the general population are not minor for pregnant women. Therefore, these patients should be monitored carefully.

Relationship between pressure fluctuations and generation of organic pollutants with different particle size distributions in a fluidized bed incinerator.

The hydrodynamic behaviors of fluidization perhaps significantly influence the uniformity of fluidization in fluidized bed incinerator. Good uniformity of fluidization expressed the air across uniformly through the bed and the particles being distributed well in the fluid stream. The aggregates, flocs and channels of particles do not happen during fluidization. The Good uniformity will maintain high heat and mass distribution to improve reaction efficiency. These parameters include the height of static bed, gas velocity, mixing and distribution of bed particle, which have rarely been studied in previous investigations. Consequently, this study examines how the hydrodynamic parameters affect the generation of organic pollutants (BTEXs and PAHs) during incineration. The statistical and power spectral analysis of the measured pressure fluctuation during incineration are used to elucidate the relationship between behaviors of fluidization and generation of pollutants during incineration. Experimental results show the organic concentration does not increase with uniformity of fluidization decreasing. The reason may be the explosion of the gas and the consequent thermal shock destroy the coalescent bubbles to form small bubbles again and enhance the efficiency of transfer of oxygen to increase combustion efficiency. Additionally, the mean amplitude and fluidized index of pressure fluctuation similarly vary with the concentration of organic pollutants. These two indices can be used to assess the efficiency of combustion. The four particle size distributions could be divided into two groups by statistical analysis. The Gaussian and narrow distributions belong to one group and the binary and flat the other. The organic concentration of the Gaussian and narrow distributions are lower than that of the other distributions. Consequently, the bed materials should maintain narrow or Gaussian distributions to maintain a good combustion efficiency during incineration.