Acute muscle wasting rate assessment and long-term mortality in critically ill trauma.

BACKGROUND AND OBJECTIVES: To evaluate the relationship between acute muscle wasting rate and long-term mortality in critically ill trauma. METHODS AND STUDY DESIGN: A single-center, retrospective study was conducted in critically ill trauma. Patients with Computed Tomography scans including the L3 vertebra within 24 hours and at 1 week after trauma were recruited. Acute muscle wasting rate was defined as the mean percent variation per day of skeletal muscle index in the first week after trauma. Multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed to determine whether acute muscle wasting rate could help predict hospital malnutrition and 1-year mortality. RESULTS: Skeletal muscle index was 49.3±10.7 cm2/m2 at baseline and decreased to 45.1±9.6 cm2/m2 (p<0.001) at 1 week and 39.8±10.8cm2/m2 (p<0.001) at 1 month after trauma. A sustained decrease of skeletal muscle index was observed from baseline up to 6 months (33.7±8.4cm2/m2, p<0.001) post trauma, and lasted for 1 year (37.7±5.6cm2/m2, p=0.004). Logistic regression analysis showed that acute muscle wasting rate was an independent risk factor for hospital malnutrition and 1-year mortality. Every 1% absolute increase of acute muscle wasting rate was associated with 1.82-fold higher odds of 1-year mortality in critically ill trauma. The area under curve of acute muscle wasting rate was 0.813 for hospital malnutrition prediction and 0.715 for 1-year mortality prediction. CONCLUSIONS: Acute muscle wasting rate was independently associated with higher 1-year mortality and hospital malnutrition in critically ill trauma.

[Experimental study on high-frequency subharmonic scattering characteristics of ultrasound contrast agent microbubbles under low ambient pressure].

Correlation between nonlinear subharmonic scattering of ultrasound contrast agent microbubbles and ambient pressure is expected to be used for local brain tissue pressure monitoring. Although high-frequency ultrasound has achieved high-resolution imaging of intracranial microvessels, the research on high-frequency subharmonic scattering characteristics of microbubbles is insufficient at present, which restricts the research progress of estimating local brain tissue pressure based on high-frequency subharmonic scattering of microbubbles. Therefore, under the excitation of 10 MHz high-frequency ultrasound, the effects of different acoustic pressures and ambient pressures on the high-frequency subharmonic scattering characteristics of three different ultrasound contrast agents including SonoVue, Sonazoid and Huashengxian were investigated in this in vitro study. Results showed that the subharmonic scattering amplitudes of the three microbubbles increased with the increase of ambient pressure at the peak negative acoustic pressures of 696, 766 and 817 kPa, and there was a favorable linear correlation between subharmonic amplitude and ambient pressure. Under the above three acoustic pressures, the highest correlation coefficient of SonoVue was 0.948 ( P = 0.03), the highest sensitivity of pressure measurement was 0.248 dB/mm Hg and the minimum root mean square error (RMSE) was 2.64 mm Hg. Sonazoid's highest correlation coefficient was 0.982 ( P < 0.01), the highest sensitivity of pressure measurement was 0.052 dB/mm Hg and the minimum RMSE was 1.51 mm Hg. The highest correlation coefficient of Huashengxian was 0.969 ( P = 0.02), the highest sensitivity of pressure measurement was 0.098 dB/mm Hg and the minimum RMSE was 2.00 mm Hg. The above in vitro experimental results indicate that by selecting ultrasound contrast agent microbubbles and optimizing acoustic pressure, the correlation between high-frequency subharmonic scattering of microbubbles and ambient pressure can be improved, the sensitivity of pressure measurement can be upgraded, and the measurement error can be reduced to meet the clinical demand for local brain tissue pressure measurement, which provided an important experimental basis for subsequent research in vivo.

Exogenous Melatonin Alleviates Skeletal Muscle Wasting by Regulating Hypothalamic Neuropeptides Expression in Endotoxemia Rats.

To investigate whether exogenous melatonin (MLT) could alleviate skeletal muscle wasting by regulating hypothalamic neuropeptides expression. Adult male Sprague Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg), followed by MLT (30 mg/kg/day) or saline for 3 days. Hypothalamic tissues and skeletal muscle were obtained on day 3. Skeletal muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box and muscle ring finger 1 as well as 3-methylhistidine (3-MH) and tyrosine release. Three hypothalamic neuropeptides (POMC, AgRP, CART) expression were detected in all groups. POMC expression knockdown was achieved by ARC injection of lentiviruses containing shRNA against POMC. Two weeks after ARC viruses injection, rats were i.p. injected with LPS (10 mg/kg) followed by MLT (30 mg/kg/day) or saline for 3 days. Brain tissues were harvested for immunostaining. In septic rats, 3-MH, tyrosine release and muscle atrophic gene expression were significantly decreased in MLT treated group. POMC and CART expression were lower while AgRP expression was higher in MLT treated group. Furthermore, in septic rats treated with MLT, muscle wasting in those with lower expression of neuropeptide POMC did not differ from those with normal POMC expression. Exogenous MLT could alleviate skeletal muscle wasting in septic rats by regulating hypothalamic neuropeptides.

Diaphragm thickness on computed tomography for nutritional assessment and hospital stay prediction in critical COVID-19.

BACKGROUND AND OBJECTIVES: To evaluate the significance of diaphragm thickness (DT) in assessing the nutritional status and predicting the length of hospital stay (LOS) of patients with COVID-19. METHODS AND STUDY DESIGN: The data of 212 patients with severe and critical COVID-19 in Wuhan, China, were retrospectively analyzed. Computed tomography (CT)-obtained DT was measured in cross-sectional images of the mediastinal window at the level of the outlet of the celiac trunk at admission and at 2 weeks, then the rate of change in DT(RCDT) at 2 weeks was calculated. Nutritional risk and malnutrition were evaluated at admission. RESULTS: A total of 91 patients were involved in the study. The mean DT was 3.06±0.58 mm (3.15±0.63 mm in male and 2.93±0.50 mm in female). DT was significantly negatively correlated with malnutrition based on Global Leadership Initiative on Malnutrition (GLIM) criteria (r=-0.324, p=0.002), Nutritional Risk Screening 2002 (NRS-2002) score (r=-0.364, p=0.000) and the Malnutrition Universal Screening Tool (MUST) score (r=-0.326, p=0.002) at admission. For the prediction of LOS ≥4 weeks in patients with COVID-19, the area under the ROC curve (AUC) of the RCDT at 2 weeks was 0.772, while the AUCs of DT, NRS-2002, MUST and Nutrition Risk in Critically Ill scores at admission were 0.751, 0.676, 0.638 and 0.699 respectively. According to the model of multiple linear regression analysis, the DT at admission (ß=-0.377, p=0.000), RCDT at 2 weeks (ß =-0.323, p=0.001), and mechanical ventilation (ß=0.192, p=0.031) were independent risk factors contributed to LOS. CONCLUSIONS: CT-obtained DT can be used as a dynamic assessment tool for evaluating the nutritional status of patients in isolation wards for COVID-19.

Application of a novel artificial perfusate based on oxygen-carrying nanoparticles in normothermic machine perfusion for porcine liver preservation after cardiac death.

OBJECTIVE: To investigate the efficacy of a novel artificial perfusate based on oxygen-carrying perfluoronaphthalene-albumin nanoparticles in normothermic machine perfusion (NMP) for preservation of porcine liver donation after cardiac death. METHODS: Artificial perfusate with perfluoronaphthalene-albumin nanoparticles was prepared at 5% albumin (w/v) and its oxygen carrying capacity was calculated. The livers of 16 Landrace pigs were isolated after 1 h of warm ischemia, and then they were divided into 4 groups and preserved continuously for 24 h with different preservation methods: cold preservation with UW solution (SCS group), NMP preservation by whole blood (blood NMP group), NMP preservation by artificial perfusate without nanoparticles (non-nanoparticles NMP group) and NMP preservation by artificial perfusate containing nanoparticles (nanoparticles NMP group). Hemodynamics, tissue metabolism, biochemical indices of perfusate and bile were monitored every 4 h after the beginning of NMP. Liver tissue samples were collected for histological examination (HE and TUNEL staining) before preservation, 12 h and 24 h after preservation. RESULTS: The oxygen carrying capacity of nanoparticles in 100 mL artificial perfusate was 6.94 µL/mmHg (1 mmHg=0.133 kPa). The hepatic artery and portal vein resistance of nanoparticles NMP group and blood NMP group remained stable during perfusion, and the vascular resistance of nanoparticles NMP group was lower than that of blood NMP group. The concentration of lactic acid in the perfusate decreased to the normal range within 8 h in both nanoparticles NMP group and blood NMP group. There were no significant differences in accumulated bile production, alanine aminotransferase and aspartate aminotransferase in perfusate between nanoparticles NMP group and blood NMP group (all P>0.05). After 24 h perfusion, the histological Suzuki score in blood NMP group and nanoparticles NMP group was lower than that in SCS group and non-nanoparticles NMP group (all P<0.05), and the quantities of TUNEL staining positive cells in blood NMP group and non-nanoparticles NMP group was higher than those in nanoparticles NMP group and SCS group 12 h and 24 h after preservation (all P<0.05). CONCLUSION: Artificial perfusate based on oxygen-carrying nanoparticles can meet the oxygen supply requirements of porcine livers donation after cardiac death during NMP preservation, and it may has superiorities in improving tissue microcirculation and alleviating ischemia-reperfusion injury.

Association of Monocyte-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios With Persistent Critical Illness in Patients With Severe Trauma.

BACKGROUND: Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio are reported to reflect the inflammation and immune status in critically ill patients, but their role in severe trauma patients with persistent critical illness remains to be elucidated. OBJECTIVE: We aimed to evaluate the relationship of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio with persistent critical illness in severe trauma patients. METHODS: In a single-center retrospective cohort study, persistent critical illness was defined as intensive care unit length of stay of more than 10 days. Monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were computed individually and categorized into 3 tertiles. Logistic regression analysis was used to assess the relationship of monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with persistent critical illness. Receiver operating characteristic curves and the Youden index were used to evaluate the discriminatory threshold of persistent critical illness. RESULTS: A total of 851 eligible patients were enrolled in the study: 328 patients with persistent critical illness and 523 without. The median levels of maximum neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio during intensive care unit stay were all higher in patients with persistent critical illness than in those without (11.46 vs. 9.13, p < .001 and 0.62 vs. 0.46, p < .001). Multivariate analysis revealed that the second (≥0.385, <0.693) and third (≥0.693) maximum monocyte-to-lymphocyte ratio tertiles were significantly associated with persistent critical illness after adjusting for confounding factors (odds ratio: 1.89, 95% confidence interval: 1.10-3.26, p = .021 and odds ratio 2.69, 95% confidence interval: 1.44-5.02, p = .002, respectively), whereas maximum neutrophil-to-lymphocyte ratio was not significantly correlated with persistent critical illness. The area under the curve for the maximum monocyte-to-lymphocyte ratio was 0.63 (95% confidence interval: 0.59-0.67), and the optimal cutoff was 0.65 for persistent critical illness. CONCLUSION: A high maximum monocyte-to-lymphocyte ratio during intensive care unit stay was independently related to persistent critical illness following severe trauma, although with limited sensitivity and specificity.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Temperature Variability Does Not Attenuate the Beneficial Effects of Therapeutic Hypothermia on Cellular Apoptosis and Endoplasmic Reticulum Stress in the Cerebral Cortex of a Swine Cardiac Arrest Model.

BACKGROUND: Endoplasmic reticulum stress (ERS) plays a vital role in mediating apoptosis in the brain following cardiac arrest (CA). Studies have shown that therapeutic hypothermia (TH) provides neuroprotection through anti-apoptosis; however, the effects of temperature variability in TH on the brain remain unclear. In this study, we investigated the different effects of temperature variability through extracorporeal membrane oxygenation on apoptosis and ERS in the brain following CA. METHODS: Eighteen male domestic pigs underwent 6-min duration of no-flow induced by ventricular fibrillation. Extracorporeal cardiopulmonary resuscitation was then performed, and the return of spontaneous circulation (ROSC) was achieved. The animals were randomly assigned to the following groups: normothermia, non-temperature variability, and temperature variability. TH (core temperature, 33-35 °C) was maintained for 24 h post-ROSC, and the animals were rewarmed for 8 h. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry for Bax and Bcl-2 transcripts and proteins, respectively, were used to investigate apoptosis in the cerebral cortex. Expression levels of the ERS molecules, GRP78 and CHOP, were also detected by qRT-PCR, and cellular morphology was evaluated using transmission electron microscopy. RESULTS: qRT-PCR and immunohistochemistry results revealed that TH significantly increased the expression levels of Bcl-2 and GRP78 and decreased that of Bax and CHOP than under normothermia conditions. Compared to the non-temperature variability group, temperature variability did not decrease the expression levels of Bcl-2 and GRP78 and not increase the levels of Bax and CHOP. Endoplasmic reticulum ultrastructural changes were significantly improved under TH. No statistical difference was observed between the temperature variability and non-temperature variability groups. CONCLUSION: TH can reduce neuronal apoptosis by ERS, while temperature variability does not attenuate this beneficial effect.

Nutritional practice in critically ill COVID-19 patients: A multicenter ambidirectional cohort study in Wuhan and Jingzhou.

BACKGROUND AND OBJECTIVES: The novel coronavirus disease (COVID-19) epidemic is spreading all over the world. With the number of cases increasing rapidly, the epidemiological data on the nutritional practice is scarce. In this study, we aim to describe the clinical characteristics and nutritional practice in a cohort of critically ill COVID-19 patients. METHODS AND STUDY DESIGN: This is a multicenter, ambidirectional cohort study conducted at 11 hospitals in Hubei Province, China. All eligible critical COVID-19 patients in the study hospital intensive care units at 00:00, March 6th, 2020, were included. Data collection was performed via written case report forms. RESULTS: A total of 44 patients were identified and enrolled, of whom eight died during the 28-day outcome follow- up period. The median interval between hospital admission and the study day was 24 (interquartile range, 13- 26) days and 52.2% (23 of 44) of patients were on invasive mechanical ventilation. The median nutrition risk in critically ill (mNUTRIC) score was 3 (interquartile range, 2-5) on the study day. During the enrolment day, 68.2% (30 of 44) of patients received enteral nutrition (EN), while 6.8% (3 of 44) received parenteral nutrition (PN) alone. Nausea and aspiration were uncommon, with a prevalence of 11.4% (5 of 44) and 6.8% (3 of 44), respectively. As for energy delivery, 69.7% (23 of 33) of patients receiving EN and/or PN were achieving their prescribed targets. CONCLUSIONS: The study showed that EN was frequently applied in critical COVID-19 patients. Energy delivery may be suboptimal in this study requiring more attention.

Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling.

BACKGROUND: In the central nervous system (CNS), connexin 43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Similar to Cx43 overexpression, abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies. However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear. METHODS: Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH models in vitro and in vivo. After ICH injury, the Cx43 mimetic peptide Gap19 was used for treatment. Ethidium bromide (EtBr) uptake assays were used to measure the opening of Cx43Hcs. Western blotting and immunofluorescence were used to measure protein expression. qRT-PCR and ELISA were used to determine the levels of cytokines. Coimmunoprecipitation (Co-IP) and the Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins. RESULTS: In this study, Cx43 expression upregulation and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19 significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition, Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture. However, Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased Yes-associated protein (YAP) nuclear translocation. This subsequently upregulated SOCS1 and SOCS3 expression and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor, verteporfin (VP), reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury. CONCLUSIONS: This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs. Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 has anti-inflammatory and neuroprotective effects after ICH injury.

Imaging of the ex vivo transglutaminase activity in liver macrophages of sepsis mice.

Sepsis is the leading cause of death in hospitalized patients and is characterized by a dysregulated inflammatory response to infection and multiple organ failure, including the liver. Transglutaminase 2 (TG2) is a multifunctional enzyme that exhibits transamidase, GTPase, and integrin-binding activities and has opposing roles in the regulation of cell growth, differentiation, and apoptosis. TG2 plays both pathogenic and protective roles in liver diseases, revealing the need to examine the activities of TG2. Here, we introduced an ex vivo imaging approach to examine the in vivo transamidase activity of TG2 based on the combination of intraperitoneal injection of 5-biotinamidopentylamine (5BAPA), a biotinylated substrate for TG2, and fluorescent streptavidin staining in frozen liver sections. Increased 5BAPA signals was observed in the livers of lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-induced sepsis mice. Pharmacological inhibition of TG2 activity ameliorated LPS-induced liver injury. 5BAPA signals were observed in TG2-expressing and F4/80-positive midzonal macrophages, providing direct evidence that activated macrophages are the major cellular source of active TG2 in the livers of sepsis mice. Further studies focusing on the activation of 5BAPA-stained midzonal macrophages may improve understanding of the molecular pathophysiology and the development of therapeutic strategies for sepsis.

Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

PURPOSE: Chlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia. METHODS: Nine cases of severe psittacosis pneumonia were diagnosed using mNGS. Retrospective analysis of the data on disease progression, new diagnosis tool, treatments, and outcomes, and the findings were summarised. RESULTS: Frequent symptoms included chills and remittent fever (100%), cough and hypodynamia (100%), and headache and myalgia (77.8%). All patients were severe psittacosis pneumonia developed respiratory failure, accompanied by sepsis in 6/9 patients. mNGS takes 48-72 h to provide the results, and help to identify diagnosis of psittacosis. Laboratory data showed normal or slightly increased leucocytes, neutrophils, and procalcitonin but high C-reactive protein levels. Computed tomography revealed air-space consolidation and ground-glass opacity, which began in the upper lobe of one lung, and spread to both lungs, along with miliary, nodular, or consolidated shadows. One patient died because of secondary infection with Klebsiella pneumoniae, while the other eight patients experienced complete recoveries. CONCLUSIONS: The use of mNGS can improve accuracy and reduce the delay in diagnosis of psittacosis. Severe psittacosis pneumonia responds well to the timely use of appropriate antibiotics.

Clinical Features of Fatal Pandemic Influenza A/H1N1 Infection Complicated by Invasive Pulmonary Fungal Infection.

BACKGROUND: Severe pneumonia caused by influenza virus infection can be secondary to invasive pulmonary fungal (IPF) infection. OBJECTIVES: This study aimed to summarize the incidence of IPF infection secondary to influenza virus infection and further explore its etiologic mechanism and high-risk factors. METHODS: All adult patients with confirmed influenza A (H1N1) virus infection admitted to the intensive care units (ICUs) of Nanjing Drum Hospital from November 2017 to March 2018 were retrospectively selected. The differences in baseline factors, risk factors, immune function and outcome parameters were studied between patients with and without IPF. RESULTS: Of the 19 critically ill patients with H1N1 infection, 11 (57.9%) developed IPF infection after 7 days of ICU admission. Two patients had proven and nine probable IPF infection. A difference in human leukocyte antigen-DR isotype (△HLA-DR; day 7-day 1) was found between the two groups. △HLA-DR (day 7-day 1) was higher in patients with no IPF infection than in those with IPF infection [(14.52 ± 14.21)% vs ( - 11.74 ± 20.22)%, P = 0.019]. The decline in HLA-DR indicated impaired immune function secondary to fungal infection in patients with H1N1 infection. CONCLUSIONS: IPF infection was diagnosed in 57.9% of critically ill patients with H1N1 virus infection after a median of 7 days following ICU admission. A continuous decline in immune function could lead to the development of IPF infections. Dynamic monitoring of immune function may help in the early detection of IPF infection.

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.

Constant light exposure aggravates POMC-mediated muscle wasting associated with hypothalamic alteration of circadian clock and SIRT1 in endotoxemia rats.

Constant light exposure is widespread in the intensive care unit (ICU) and could increase the rate of brain dysfunction as delirium and sleep disorders in critical patients. And the activation of hypothalamic neuropeptides is proved to play a crucial role in regulating hypercatabolism, especially skeletal muscle wasting in critical patients, which could lead to serious complications and poor prognosis. Here we investigated the hypothesis that constant light exposure could aggravate skeletal muscle wasting in endotoxemia rats and whether it was associated with alterations of circadian clock and hypothalamic proopiomelanocortin(POMC) expression. Fifty-four adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide(LPS) or saline, subjected to constant light or a 12:12 h light-dark cycle for 7 days. On day 8, rats were sacrificed across six time points in 24 h and hypothalamus tissues and skeletal muscle were obtained. Rates of muscle wasting were measured by 3-methylhistidine(3-MH) and tyrosine release as well as expression of two muscle atrophic genes, muscle ring finger 1(MuRF-1) and muscle atrophy F-box(MAFbx). The expression of circadian clock genes, silent information regulator 1(SIRT1), POMC and hypothalamic inflammatory cytokines were also detected. Results showed that LPS administration significantly increased hypothalamic POMC expression, inflammatory cytokine levels and muscle wasting rates. Meanwhile constant light exposure disrupted the circadian rhythm, declined the expression of SIRT1 as well as aggravated hypothalamic POMC overexpression and skeletal muscle wasting in rats with endotoxemia. Taken together, the results demonstrated that constant light exposure could aggravate POMC-mediated skeletal muscle wasting in endotoxemia rats, which is associated with alteration of circadian clocks and SIRT1 in the hypothalamus.

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.

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.

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.

Severity-specific alterations in CBF, OEF and CMRO2 in cirrhotic patients with hepatic encephalopathy.

OBJECTIVES: To assess how the severity of hepatic encephalopathy (HE) affects perfusion and metabolic changes in cirrhotic patients and the association between severity and liver disease and anemia. METHODS: The study groups comprised 31 healthy subjects and 33 cirrhotic patients who underwent MR examinations, and blood and neuropsychological tests. Of the cirrhotic patients, 14 were unaffected, and 11 had covert HE (CHE) and 8 overt HE (OHE). Global cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2) were noninvasively measured by phase-contrast and T2-relaxation-under-spin-tagging MRI. Correlations were performed between MR measurements, hematocrits, ammonia levels, Child-Pugh scores and neuropsychological test scores. RESULTS: Compared with the values in healthy subjects, CBF was higher in unaffected patients, the same in CHE patients and lower in OHE patients, OEF was higher in all patients, and CMRO2 was the same in unaffected and CHE patients and lower in OHE patients. Hematocrit was negatively correlated with CBF and OEF, but not with CMRO2. Ammonia level was negatively correlated with CBF and CMRO2, and Child-Pugh score was negatively correlated with CMRO2. CONCLUSIONS: The severity-associated alterations in cirrhotic patients indicate that homeostasis of oxygen delivery and oxidative metabolism in HE is regulated by multiple mechanisms. These physiological alterations appeared to be associated with the degree of anemia, ammonia level, and liver function. KEY POINTS: • CBF, OEF and CMRO2 did not change monotonically with HE progression. • Anemia possibly contributed to CBF and OEF changes in cirrhotic patients. • Liver dysfunction mainly contributed to changes in CMRO2 in cirrhotic patients.