Association of longitudinal changes in skeletal muscle mass with prognosis and nutritional intake in acutely hospitalized patients with abdominal trauma: a retrospective observational study.

Background: The objective of this study was to explore whether longitudinal changes in skeletal muscle mass, from hospital admission to 3 weeks post-trauma, are associated with poor prognosis and nutritional intake in acutely hospitalized patients with abdominal trauma. Methods: A single-center retrospective observational review was conducted on 103 patients with abdominal trauma admitted to the Affiliated Jinling Hospital, Medical School of Nanjing University between January 2010 and April 2020. Skeletal muscle mass was assessed by abdominal computed tomography (CT) performed within 14 days before surgery and on post-trauma days 1-3 (week 0), 7-10 (week 1), 14-17 (week 2), and 21-24 (week 3). The skeletal muscle index (SMI) at L3, change in SMI per day (ΔSMI/day), and percent change in SMI per day (ΔSMI/day [%]) were calculated. The receiver-operating characteristic (ROC) curve was used to evaluate the discriminatory performance of ΔSMI/day (%) for mortality. Linear correlation analysis was used to evaluate the associations between ΔSMI/day (%) and daily caloric or protein intake. Results: Among the included patients, there were 91 males and 12 females (mean age ± standard deviation 43.74 ± 15.53 years). ΔSMI4-1/d (%) had a ROC-area under the curve of 0.747 (p = 0.048) and a cut-off value of -0.032 for overall mortality. There were significant positive correlations between ΔSMI4-1/d (%) and daily caloric intake and protein intake (Y = 0.0007501*X - 1.397, R2 = 0.282, R = 0.531, p < 0.001; Y = 0.008183*X - 0.9228, R2 = 0.194, R = 0.440, p < 0.001). Δ SMI/day (%) was positively correlated with daily caloric intake ≥80% of resting energy expenditure in weeks 2, 3, and 1-3 post-trauma and with protein intake >1.2 g/kg/d in weeks 3 and 1-3 post-trauma. Conclusion: Loss of skeletal muscle mass is associated with poor prognosis and nutritional intake in patients admitted to hospital with abdominal trauma.

Subcutaneous Adipose Tissue Is Associated with Acute Kidney Injury after Abdominal Trauma Based on the Generalized Propensity Score Approach: A Retrospective Cohort Study.

INTRODUCTION: Obesity is associated with an increased risk of acute kidney injury (AKI) after trauma. However, the associations between different adipose tissue depots and AKI remain unknown. Our study aimed to quantify the effect of abdominal adiposity on AKI in trauma patients. METHODS: We performed a retrospective cohort study of abdominal trauma patients who were admitted to our hospital from January 2010 to March 2020. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured at the level of the third lumbar vertebra using computed tomography. Causal modeling based on the generalized propensity score was used to quantify the effects of body mass index (BMI), VAT, and SAT on AKI. RESULTS: Among 324 abdominal trauma patients, 67 (20.68%) patients developed AKI. Patients with AKI had higher BMI (22.46 kg/m2 vs. 22.04 kg/m2, p = 0.014), higher SAT areas (89.06 cm2 vs. 83.39 cm2, p = 0.151), and higher VAT areas (140.02 cm2 vs. 91.48 cm2, p = 0.001) than those without AKI. By using causal modeling, we found that the risk of developing AKI increased by 8.3% (p = 0.001) and 4.8% (p = 0.022) with one unit increase in BMI (per 1 kg/m2) and ten units increase in SAT (per 10 cm2), respectively. However, VAT did not show a significant association with AKI (p = 0.327). CONCLUSION: SAT, but not VAT, increased the risk of AKI among abdominal trauma patients. Measurement of SAT might help identify patients at higher risk of AKI.

Real-Time Prediction of Sepsis in Critical Trauma Patients: Machine Learning-Based Modeling Study.

BACKGROUND: Sepsis is a leading cause of death in patients with trauma, and the risk of mortality increases significantly for each hour of delay in treatment. A hypermetabolic baseline and explosive inflammatory immune response mask clinical signs and symptoms of sepsis in trauma patients, making early diagnosis of sepsis more challenging. Machine learning-based predictive modeling has shown great promise in evaluating and predicting sepsis risk in the general intensive care unit (ICU) setting, but there has been no sepsis prediction model specifically developed for trauma patients so far. OBJECTIVE: To develop a machine learning model to predict the risk of sepsis at an hourly scale among ICU-admitted trauma patients. METHODS: We extracted data from adult trauma patients admitted to the ICU at Beth Israel Deaconess Medical Center between 2008 and 2019. A total of 42 raw variables were collected, including demographics, vital signs, arterial blood gas, and laboratory tests. We further derived a total of 485 features, including measurement pattern features, scoring features, and time-series variables, from the raw variables by feature engineering. The data set was randomly split into 70% for model development with stratified 5-fold cross-validation, 15% for calibration, and 15% for testing. An Extreme Gradient Boosting (XGBoost) model was developed to predict the hourly risk of sepsis at prediction windows of 4, 6, 8, 12, and 24 hours. We evaluated model performance for discrimination and calibration both at time-step and outcome levels. Clinical applicability of the model was evaluated with varying levels of precision, and the potential clinical net benefit was assessed with decision curve analysis (DCA). A Shapley additive explanation algorithm was applied to show the effect of features on the prediction model. In addition, we trained an L2-regularized logistic regression model to compare its performance with XGBoost. RESULTS: We included 4603 trauma patients in the study, 1196 (26%) of whom developed sepsis. The XGBoost model achieved an area under the receiver operating characteristics curve (AUROC) ranging from 0.83 to 0.88 at the 4-to-24-hour prediction window in the test set. With a ratio of 9 false alerts for every true alert, it predicted 73% (386/529) of sepsis-positive timesteps and 91% (163/179) of sepsis events in the subsequent 6 hours. The DCA showed our model had a positive net benefit in the threshold probability range of 0 to 0.6. In comparison, the logistic regression model achieved lower performance, with AUROC ranging from 0.76 to 0.84 at the 4-to-24-hour prediction window. CONCLUSIONS: The machine learning-based model had good discrimination and calibration performance for sepsis prediction in critical trauma patients. Using the model in clinical practice might help to identify patients at risk of sepsis in a time window that enables personalized intervention and early treatment.

Longitudinal D-Dimer Trajectories and the Risk of Mortality in Abdominal Trauma Patients: A Group-Based Trajectory Modeling Analysis.

This study aimed to identify the long-term D-dimer trajectory patterns and their associations with in-hospital all-cause mortality in abdominal trauma patients. This is a retrospective cohort study of general adult abdominal trauma patients admitted to Jinling Hospital (Nanjing, China) between January 2010 and April 2020. Group-based trajectory modeling was applied to model D-dimer trajectories over the first 50 days post-trauma. A multivariable logistic regression was performed to estimate the associations between D-dimer trajectories and in-hospital all-cause mortality. A total of 309 patients were included. We identified four distinct D-dimer trajectories: group 1 (57.61%; "stable low"), group 2 (28.16%; "moderate-decline"), group 3 (8.41%; "high-rapid decline"), and group 4 (5.83%; "high-gradual decline"). The SOFA score (p = 0.005) and ISS (p = 0.001) were statistically higher in groups 3 and 4 than in groups 1 and 2. The LMWH and UFH did not differ between groups 3 and 4. Compared with the patients in group 1, only the patients in group 4 were at a higher risk of in-hospital all-cause mortality (OR = 6.94, 95% CI: 1.20-40.25). The long-term D-dimer trajectories post-trauma were heterogeneous and associated with mortality. An initially high and slowly-resolved D-dimer might function as the marker of disease deterioration, and specific interventions are needed.

High Fat-to-Muscle Ratio Was Associated with Increased Clinical Severity in Patients with Abdominal Trauma.

Overweight and moderate obesity confer a survival benefit in chronic diseases such as coronary artery disease and chronic kidney disease, which has been termed the "obesity paradox". However, whether this phenomenon exists in trauma patients remains controversial. We performed a retrospective cohort study in abdominal trauma patients admitted to a Level I trauma center in Nanjing, China between 2010 and 2020. In addition to the traditional body mass index (BMI) based measures, we further examined the association between body composition-based indices with clinical severity in trauma populations. Body composition indices including skeletal muscle index (SMI), fat tissue index (FTI), and total fat-to-muscle ratio (FTI/SMI) were measured using computed tomography. Our study found that overweight was associated with a four-fold risk of mortality (OR, 4.47 [95% CI, 1.40-14.97], p = 0.012) and obesity was associated with a seven-fold risk of mortality (OR, 6.56 [95% CI, 1.07-36.57], p = 0.032) compared to normal weight. Patients with high FTI/SMI had a three-fold risk of mortality (OR, 3.06 [95% CI, 1.08-10.16], p = 0.046) and double the risk of an intensive care unit length of stay ≥ 5 d (OR, 1.75 [95% CI, 1.06-2.91], p = 0.031) compared to patients with low FTI/SMI. The obesity paradox was not observed in abdominal trauma patients, and high FTI/SMI ratio was independently associated with increased clinical severity.

Early parenteral nutrition comparing to enteral nutrition cannot reduce 28-day mortality in critically ill patients: a retrospective comparative cohort study based on the MIMIC­IV database.

Background: Enteral nutrition (EN) is recommended as the first choice by guidelines for critical ill patients. But the timing of safe and effective delivery of parenteral nutrition (PN) is unclear and the results of previous studies are controversial. There is insufficient evidence for the use of early PN, so we designed this cohort study to compared the clinical outcomes of critical ill patients who received early PN with those who did not. Methods: This retrospective study conducted using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients who received nutrition therapy within 3 days of ICU admission were included and we categorized them as patients who received any kind of PN (PN group) or only enteral nutrition (EN group). Confounding factors were adjusted by propensity-score matching (PSM). The primary outcome was the 28-day mortality rate, and secondary outcomes included length of stay (LOS) in the hospital and ICU, hospital infection, and mechanical ventilation time. Results: A total of 5,019 patients (PN group, 357; EN group, 4,662) were included in the analyses. The 28-day mortality rates showed no significant intergroup difference (EN, 22.3% vs. PN, 20.2%; P=0.378). The PN group showed a shorter median ICU LOS (EN, 8.14 vs. PN, 6.89 days, P=0.00955), and a longer median hospital LOS (PN, 21.55 vs. EN, 15.1 days, P<0.001). After PSM, each group included 355 patients, with no significant intergroup difference in the 28-day mortality rate (EN, 18.9% vs. PN, 20.3%; P=0.705). The PN group still showed a longer hospital LOS (median LOS: PN, 21.45 vs. EN, 14.81 days, P<0.001), but the other outcomes showed no differences. Conclusions: PN within 3 days of ICU admission did not reduce the 28-day mortality rate and could extend hospital LOS. This study supports further fundamental and clinical research to ascertain the effect of PN for ICU patients.

Novel fast pathogen diagnosis method for severe pneumonia patients in the intensive care unit: randomized clinical trial.

Background: Severe pneumonia is one of the common acute diseases caused by pathogenic microorganism infection, especially by pathogenic bacteria, leading to sepsis with a high morbidity and mortality rate. However, the existing bacteria cultivation method cannot satisfy current clinical needs requiring rapid identification of bacteria strain for antibiotic selection. Therefore, developing a sensitive liquid biopsy system demonstrates the enormous value of detecting pathogenic bacterium species in pneumonia patients. Methods: In this study, we developed a tool named Species-Specific Bacterial Detector (SSBD, pronounce as 'speed') for detecting selected bacterium. Newly designed diagnostic tools combining specific DNA-tag screened by our algorithm and CRISPR/Cas12a, which were first tested in the lab to confirm the accuracy, followed by validating its specificity and sensitivity via applying on bronchoalveolar lavage fluid (BALF) from pneumonia patients. In the validation I stage, we compared the SSBD results with traditional cultivation results. In the validation II stage, a randomized and controlled clinical trial was completed at the ICU of Nanjing Drum Tower Hospital to evaluate the benefit SSBD brought to the treatment. Results: In the validation stage I, 77 BALF samples were tested, and SSBD could identify designated organisms in 4 hr with almost 100% sensitivity and over 87% specific rate. In validation stage II, the SSBD results were obtained in 4 hr, leading to better APACHE II scores (p=0.0035, ANOVA test). Based on the results acquired by SSBD, cultivation results could deviate from the real pathogenic situation with polymicrobial infections. In addition, nosocomial infections were found widely in ICU, which should deserve more attention. Conclusions: SSBD was confirmed to be a powerful tool for severe pneumonia diagnosis in ICU with high accuracy. Funding: National Natural Science Foundation of China. The National Key Scientific Instrument and Equipment Development Project. Project number: 81927808. Clinical trial number: This study was registered at https://clinicaltrials.gov/ (NCT04178382).

Low skeletal muscle mass predicts poor clinical outcomes in patients with abdominal trauma.

OBJECTIVE: The aim of this study was to investigate whether low skeletal muscle mass is associated with clinical outcomes in patients with abdominal trauma. METHODS: Patients presenting to our institution with abdominal trauma from January 2010 to April 2020 were retrospectively included. Low skeletal muscle mass was defined, using computed tomography, as skeletal muscle index (SMI) at the third lumbar vertebra below the lowest sex-specific quartile within 1 wk of admission. Clinical outcomes such as complications, hospital stay, and hospital cost were recorded, and univariate and multivariate analyses were performed. RESULTS: Among 684 patients, 451 were eligible. Of these, 112 (24.8%) were classified as having low skeletal muscle mass, based on SMI diagnostic cutoff values (42.08 cm2/m2 for men and 37.35 cm2/m2 for women). Low skeletal muscle mass was significantly associated with longer hospital length of stay, longer intensive care length of stay, higher cost, higher frequency of mechanical ventilation, longer duration of vasopressor use, and higher incidence of massive transfusion and overall complications (P < 0.05). Subgroup analysis showed that pneumonia, acute gastrointestinal dysfunction, cholecystitis, digestive tract fistula, gastric fistula, and intestinal fistula were significantly associated with low skeletal muscle mass (P < 0.05). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for overall complications (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.33-4.49; P = 0.004), hospital length of stay (OR, 3.49; 95% CI, 1.96-6.20; P < 0.001), and hospital cost (OR, 2.67; 95% CI, 1.48-4.80; P = 0.001). CONCLUSIONS: Low skeletal muscle mass could be an independent predictor of poor clinical outcomes in patients with abdominal trauma.

Sarcopenia associated with 90-day readmission and overall survival after abdominal trauma.

BACKGROUND AND OBJECTIVES: It is widely recognized that sarcopenia increases postoperative complications in trauma patients. However, the effects on prognosis remain unclear. This study aimed to evaluate the impact of sarcopenia on 90-day readmission and overall survival (OS) in abdominal trauma patients. METHODS AND STUDY DESIGN: 485 consecutive patients who underwent abdominal surgery after trauma in our institution were enrolled. Sarcopenia was diagnosed with low muscle mass and low muscle strength-handgrip. Multivariate logistic regression analysis was performed to identify factors that contributed to 90-day readmission and OS. Cox logistic regression analysis was used to assess the relationship between sarcopenia and OS. RESULTS: Sarcopenia was present in 120 of 485 patients (24.7%) with abdominal trauma within one week after admission based on the diagnostic cut-off values (40.9 cm2/m2 for men and 36.8 cm2/m2 for women). 90-day readmission was significantly higher in the sarcopenia group (p=0.019), and OS lower in the sarcopenia group (p=0.025). Sarcopenia was an independent predictor of 90-day readmission [odds ratio (OR): 5.34, 95% confidence interval (CI): 2.52-11.3]. CONCLUSIONS: Sarcopenia was associated with high 90-day readmission and low OS in abdominal trauma patients, and it was an independent risk factor for 90-day readmission.

A Comparison of Gastric and Jejunal Feeding in Hypercatabolism Associated With Hypothalamic AMPK-Autophagy-POMC in Endotoxemic Rats.

BACKGROUND: Hypercatabolism is associated with increased infectious rates and mortality in critically ill patients. Enteral nutrition (EN) is usually used to counteract hypercatabolism. However, the impact of different routes of EN on hypercatabolism remains unknown. Here, we compared the impact of gastric feeding (GF) and jejunal feeding (JF) on gastrointestinal hormones and hypercatabolism, which is associated with hypothalamic adenosine 5'-monophosphate-activated protein kinase (AMPK)-autophagy-proopiomelanocortin (POMC). METHODS: Sixty adult male Sprague-Dawley rats were divided into 5 groups: Sham and lipopolysaccharide (LPS) groups fed a standard chow diet, a pair-fed group that was a subset of saline-treated rats pair-fed with the LPS group, and LPS + JF and LPS + GF groups (received EN via jejunal and gastric tube, respectively, for 3 days [100 kcal/kg/d]). Hypercatabolism was measured by insulin resistance, muscle protein synthesis, and atrophy. Serum gastrointestinal hormones, hypothalamic ghrelin, growth hormone secretagogue receptor-1α (GHS-R1α), and AMPK-autophagy-POMC markers were also detected. RESULTS: GF increased serum total, acylated, desacylated, and hypothalamic ghrelin and decreased glucagon-like peptide-1 (GLP-1). But no effect on pancreatic polypeptide (PYY) and hypothalamic GHS-R1α was observed. JF showed no effect on hypothalamic ghrelin, GHS-R1α, and serum total, acylated, and desacylated ghrelin and even further aggravated GLP-1 and PYY. GF could effectively augment hypothalamic AMPK-autophagy-POMC and hypercatabolism. However, JF showed no effect on hypothalamic AMPK-autophagy-POMC and hypercatabolism. CONCLUSIONS: GF could activate hypothalamic AMPK-autophagy and suppress POMC expression via gastrointestinal hormones to ameliorate hypercatabolism compared with JF, which suggested that GF may be the preferred route of EN in endotoxemic rats.

Predictive value of transabdominal intestinal sonography in critically ill patients: a prospective observational study.

BACKGROUND: This study examined the feasibility of transabdominal intestinal ultrasonography in evaluating acute gastrointestinal injury (AGI). METHODS: A total of 116 patients were included. Intestinal ultrasonography was conducted daily within 1 week after admission to the intensive care unit. Ultrasonography indicators including intestinal diameter, changes in the intestinal folds, thickness of the intestinal wall, stratification of the intestinal wall, and intestinal peristalsis (movement of the intestinal contents) were observed to determine the acute gastrointestinal injury ultrasonography (AGIUS) score. The gastrointestinal and urinary tract sonography ultrasound (GUTS) protocol score was also calculated. During the first week of the study, the gastrointestinal failure (GIF) score was determined daily. The correlations between transabdominal intestinal scores (AGIUS and GUTS) and the GIF score were analyzed to clarify the feasibility of evaluating AGI through observation of the intestine. The utility of intestinal ultrasonography indicators in predicting feeding intolerance was investigated to improve the ability of clinicians to manage AGI. RESULTS: A total of 751 ultrasonic examinations were performed with 511 images (68%) considered to be of "good quality." AGIUS and GUTS scores differed significantly between AGI patients (GIF score 0-2) and non-AGI patients (GIF score 3-4) (p < 0.001). Both scores correlated positively with GIF score (r = 0.54, p < 0.001; r = 0.66, p < 0.001). These ultrasonography indicators could predict feeding intolerance, with an area under the receiver operating characteristic curve of 0.60 (0.48-0.71; intestinal diameter), 0.76 (0.67-0.85; intestinal folds), 0.71 (0.62-0.80; wall thickness), 0.77 (0.69-0.86; wall stratification), and 0.78 (0.68-0.88; intestinal peristalsis). Compared to patients with a normal rate of peristalsis (5-10/min), patients with abnormal peristalsis rates (< 5/min or > 10/min) have increased risk for feeding intolerance (16/83 vs. 25/33, p < 0.001). CONCLUSIONS: The transabdominal intestinal ultrasonography represents an effective means for assessing gastrointestinal injury in critically ill patients. Intestinal ultrasonography indicators, especially the degree of intestinal peristalsis, may be used to predict feeding intolerance. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03589248. Registered 04 July 2018-retrospectively registered.

Hypothalamic AMPK-induced autophagy ameliorates hypercatabolism in septic rats by regulating POMC expression.

Hypercatabolism plays a critical role in the pathogenesis of post-critical care debility in critical patients. Central nervous system may exerte a critical role in the regulation of hypercatabolism. However, little is known about the exact mechanisms of the central role. Here, we reported that actived hypothalamic AMP-activated protein kinase (AMPK)-induced autophagy modulated the expression of POMC to ameliorate hypercatabolism in septic rats. Firstly, rats were i.c.v. injected with the lentiviral vector containing shRNA against POMC. Two weeks after injections, rats were intraperitoneally injected with LPS or saline. Twenty-four hours later, blood, skeletal muscle and hypothalamus tissues were obtained. Hypercatabolism markers and neuropeptides expression were detected. Then, rats were injected with AICAR or saline into third ventricle and promptly intraperitoneally injected with LPS or saline. Twenty-four hours after infection, blood, skeletal muscle and hypothalamus tissues were obtained. Hypercatabolism, hypothalamic AMPK-induced autophagy markers and neuropeptides expression were also detected. Results showed that sepsis would decrease the level of hypothalamic autophagy accompany with the alterations of POMC expression and hypercatabolism. Knocking out hypothalamus POMC expression could significantly ameliorate hypercatabolism. Moreover, Central activation of AMPK-induced autophagy pathway via third ventricle injection of AICAR, an AMPK activator, could efficiently ameliorate hypercatabolism as well as attenuate the elevated POMC expression rather than other neuropeptides. Taken together, these results suggested that hypothalamic AMPK-autophagy pathway as a regulatory pathway for POMC expression was essential for hypercatabolism during sepsis. And hypothalamic AMPK-autophagy activation could attenuate the POMC expression to ameliorate hypercatabolism. Pharmaceuticals with the ability of activating hypothalamic AMPK-autophagy pathway may be a therapeutic potential for hypercatabolism in septic patients.

Efficacy and safety of pectin-supplemented enteral nutrition in intensive care: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Enteral nutrition (EN) can improve clinical outcomes as an important treatment in critically ill patients. However, when patients suffer from gastrointestinal function disorders, intestinal intolerance occurs and EN administration may be delayed and even fails to perform. Pectin, a structural heteropolysaccharide, could protect gastrointestinal function from disorders in many gastrointestianl diseases. The present study aimed to determine whether pectin-supplemented EN was safe and improved clinical outcomes in intensive care unit (ICU) patients. METHODS AND STUDY DESIGN: Patients enrolled in ICU from August 2014 to January 2015 were randomized to EN group and pectin-supplemented EN group (PEC/EN group). Both group received isonitrogenous, isocaloric EN support within 36 hours after ICU admission, and last for 6 days. The primary endpoints were 30-day mortality and gastrointestinal intolerance. RESULTS: There were 125 patients included in this study (63 in EN group, and 62 in PEC/EN group). The results showed that the 30-day mortality was 4.8% in EN group and 1.61% in PEC/EN group (p=0.317). PEC/EN group had a smaller gastrointestinal intolerance rate than EN group (41.3% vs 27.4%, p=0.04). Furthermore, there were shorter times to reach full EN (13.0±5.12 vs 9.99±1.91, p=0.05), length of ICU stay (17.9±9.72 vs 13.8±8.59, p<0.001), and length of hospital stay (32.9±19.0 vs 23.4±13.2, p<0.001) in EN group than those in PEC/EN group. CONCLUSIONS: These results revealed that pectin- supplemented EN was safe, and could improve clinical outcomes in ICU patients.

Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides.

Sepsis, always developing muscle wasting, contributes to serious complications and mortality. Mild hypothermia has been reported to have protective effects on the prognosis of septic patients. However, the underlying mechanisms remain unclear. We therefore hypothesized that mild hypothermia could ameliorate muscle wasting during sepsis and whether it was associated with hypothalamus AMPK-induced autophagy and neuropeptides. Adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline. Mild hypothermia was instantly induced at 33 °C for 3h after LPS injected. Meanwhile, the control and sepsis groups were simultaneously placed on the thermal mattress to maintain the a normal temperature in control group whatever the changes induced by anesthesia. Twenty-four hours after injection, skeletal muscle and hypothalamus tissues were obtained. Muscle wasting was measured by the mRNA expression of two muscle atrophic genes, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic AMPK-induced autophagy markers and neuropeptides expression were also detected. Results showed that LPS administration significantly decreased hypothalamic AMPK-induced autophagy together with muscle wasting. Also, increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuro-peptides Y (NPY) and decreased agouti-related protein (AgRP) were observed. Mild hypothermia significantly increased hypothalamic AMPK-induced autophagy and ameliorated LPS-induced muscle wasting, and attenuated the alteration of neuropeptides, POMC, CART and NPY. In conclusion, mild hypothermia could alleviate muscle wasting by LPS injection, which was associated with reversing the level of hypothalamic AMPK-induced autophagy and the alteration of neuropeptides. These results suggested that mild hypothermia could be a potential treatment concept and a novel mechanism in management of muscle wasting in critically ill patients.

Acute Colonic Pseudo-Obstruction with Feeding Intolerance in Critically Ill Patients: A Study according to Gut Wall Analysis.

Objective. To compare the differences between acute colonic pseudo-obstruction (ACPO) with and without acute gut wall thickening. Methods. ACPO patients with feeding tolerance were divided into ACPO with no obvious gut wall thickening (ACPO-NT) group and ACPO with obvious acute gut wall thickening (ACPO-T) group according to computed tomography and abdominal radiographs. Patients' condition, responses to supportive measures, pharmacologic therapy, endoscopic decompression, and surgeries and outcomes were compared. Results. Patients in ACPO-T group had a significantly higher APACHE II (11.82 versus 8.25, p = 0.008) and SOFA scores (6.47 versus 3.54, p < 0.001) and a significantly higher 28-day mortality (17.78% versus 4.16%, p = 0.032) and longer intensive care unit stage (4 versus 16 d, p < 0.001). Patients in ACPO-NT group were more likely to be responsive to supportive treatment (62.50% versus 24.44%, p < 0.001), neostigmine (77.78% versus 17.64%, p < 0.001), and colonoscopic decompression (75% versus 42.86%, p = 0.318) than those in ACPO-T group. Of the patients who underwent ileostomy, 81.25% gained benefits. Conclusions. ACPO patients with gut wall thickening are more severe and are less likely to be responsive to nonsurgical treatment. Ileostomy may be a good option for ACPO patients with gut wall thickening who are irresponsive to nonsurgical treatment.

Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats.

Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 µg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 µg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation.

Estrogen Maintains Skeletal Muscle in Septic Rats Associated with Altering Hypothalamic Inflammation and Neuropeptides.

Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17ß-estradiol (1 mg/kg) or saline. Twenty-four hours later, all animals were killed and their hypothalamus and skeletal muscles were harvested for analysis. Muscle wasting markers, hypothalamic neuropeptides, and hypothalamic inflammatory markers were measured. As a result, lipopolysaccharide administration caused a significant increase in muscle wasting, hypothalamic inflammation, and anorexigenic neuropeptides (POMC and CART) gene expression, and a significant decrease in orexigenic neuropeptides (AgRP and NPY) gene expression. Administration of estrogen signifcantl attenuated lipopolysaccharide-induced muscle wasting (body weight and extensor digitorum longus loss [52 and 62 %], tyrosine and 3-methylhistidine release [17 and 22 %], muscle ring fnger 1 [MuRF-1; 65 %], and muscle atrophy F-box [MAFbx] gene expression), hypothalamic inflammation (Tumor necrosis factor-α and interlukin-1ß [69 and 70%]) as well as alteration of POMC, CART and AgRP (61, 37, and 1008 %) expression.In conclusion, estrogen could alleviate sepsis-induced muscle wasting and it was associated with reducing hypothalamic inflammation and alteration of hypothalamic neuropeptides.

The Addition of Dexmedetomidine to Analgesia for Patients After Abdominal Operations: A Prospective Randomized Clinical Trial.

BACKGROUND: Postoperative pain and anxiety are two common factors influencing patient's recovery. Benefits and safety in the use of sedative agents after abdominal operations to improve recovery are not well known. The present study is to evaluate the efficacy and safety of dexmedetomidine use in this population. METHODS: A prospective randomized controlled trial of 145 patients undergoing abdominal operations was conducted in the Surgical Intensive Care Unit of Jinling Hospital between October and December 2015. Thirty-two patients were excluded, and 113 were included and divided into the experimental group (59 patients) receiving dexmedetomidine and analgesics for 72 h after abdominal operations, and the control group (54 patients) receiving only analgesics. Postoperative pain, inflammatory response, recovery of gastrointestinal function, adverse events, and sedation level were analyzed. RESULTS: Pain scores, assessed by Prince Henry Pain Scale (PHPS), in the experimental group were significantly lower than in the control group on the first (1.53 vs. 2.07, p ≤ 0.01), second (1.07 vs. 1.63, p ≤ 0.01), and third day (1.08 vs. 1.82, p = 0.01). Time to defecation was 0.60 days shorter in the experimental group than the control group (2.51 vs. 3.11, p = 0.01). There was no significant difference between inflammatory responses in the two groups (p > 0.05). Both groups had similar blood pressure, heart rate, prevalence of bradycardia, and hypotension requiring interventions (p > 0.05). CONCLUSIONS: The addition of dexmedetomidine to analgesia after abdominal operations is safe and could enhance gastrointestinal function recovery and pain control when monitored carefully. The capacity of dexmedetomidine to attenuate inflammatory responses requires further investigation.

Evaluation of Transversus Abdominis Plane (TAP) Block in Hernia Surgery: A Meta-analysis.

BACKGROUND: Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery. METHODS: A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications. RESULTS: The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] -11.40 mg, -22.41 to -0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P<0.001), the pain scores on rest 24 hours after surgery (WMD: -0.29, -0.55 to -0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: -0.70, -1.33 to -0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group. CONCLUSIONS: Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.