[Expert consensus on late stage of critical care management].

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

[Clinical efficacy of damage control orthopaedics in treatment of patients with severe traumatic brain injury combined with limb fracture].

Objective: To explore the clinical efficacy of damage control orthopaedics in treatment of patients with severe traumatic brain injury combined with limb fracture. Methods: Total 149 patients with sTBI combined with limb fracture treated in Emergency Surgery Department of Shandong University Qilu Hospital from January, 2011 to December, 2018 were collected. Patients that were treated with immediate definitive fixation before March 31st, 2013 were included into the routine treatment group (group A, 47 cases), and that were treated with damage control orthopaedics (DCO) after April 1st, 2013 were included into the DCO group (group B, 102 cases). The clinical data during hospitalization and prognosis 3 months after injury was analyzed retrospectively. Then according to the risk of postoperative ICP increase, the two groups were divided into low risk subgroup and high risk subgroup. The postoperative ICP, length of stay and GOS score were statistically analyzed. Results: There were no statistically significant differences in sex, age, preoperative GCS score, imaging type of lesion and initial intraoperative ICP between the two groups. The postoperative ICP and incidence of coagulation dysfunction were significantly higher in group A [(17.1±4.6) mmHg, 29.8%] than that in group B[(15.0±4.3) mmHg, 13.7%] separately(P<0.05), and there was no significant difference of length of stay and GOS score between the two groups (P=0.475 and 0.097, respectively). As for the subgroup with low risk of postoperative ICP increase, there was no significant difference in postoperative ICP and GOS score between group A and B, and the length of stay of group B was significantly longer than that of group A (P<0.05). As for the subgroup with high risk of postoperative ICP increase, there was no significant difference in the length of stay between group A and B (P=0.667), and for group A the postoperative ICP was higher and GOS score was lower than that of group B (P<0.05). Conclusions: For patients with sTBI combined with limb fracture, the application of DCO should be based on the severity of traumatic brain injury. For patients with high risk of postoperative ICP increase, DCO can significantly improve the prognosis of patients.

[Changes of sex hormones and sex hormone-binding globulin levels in male adults with hyperthyroidism before and after antithyroid drug treatment].

Objective: To observe the changes of sex hormone and sex hormone-binding globulin (SHBG) levels in young male patients with hyperthyroidism before and after antithyroid drug (ATD) treatment. Methods: Between January 2015 and July 2016, forty male patients with hyperthyroidism aged 19-52 years (with an median age of 33.1 years) were enrolled in the Department of Endocrinology of Peking Union Medical College Hospital. Blood samples were taken before treatment and at 1 month, 2 months, 3 months and 5 months after treatment to evaluate thyroid function, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone(T), free testosterone(FT), estradiol(E2), prolactin and SHBG. Results: A total of 40 patients were enrolled but only 35 patients completed the follow-up. The patients had high levels of thyroid function, SHBG and sex hormones before treatment. Before treatment, free thyroxine (FT(4)), free triiodothyronine (FT(3)), SHBG, LH, estradiol, testosterone and free testosterone was (0.30±0.12) pmol/L, (9.68±4.73) pmol/L, (146±111) nmol/L, (8.41±3.61) U/L, (19.9±7.7) pmol/L, (29.9±9.5) nmol/L and (0.24±0.08) nmol/L, respectively. After treatment, the level of triiodothyronine, thyroxine, FT(3) and FT(4) gradually decreased to normal (all P<0.001). Thyroid stimulating hormone (TSH) gradually increased to normal (P<0.001). LH and estradiol levels gradually decreased (all P<0.001). FSH decreased but the difference was not statistically significant. Prolactin did not change significantly. Testosterone and SHBG levels decreased significantly while the levels of free testosterone, free testosterone percentage (FT%), bio-available testosterone (BAT), bio-available testosterone percentage (BAT%), free androgen index (FAI) gradually increased and stabilized (all P<0.001). The difference was not statistically significant between T/LH and E2/LH before and after treatment (all P>0.05). However FT/LH gradually increased and its difference was statistically significant (P<0.001). Conclusion: The levels of LH, estradiol, testosterone and SHBG in male patients with hyperthyroidism significantly increased, while the free testosterone level decreased, but they all gradually returned to normal with the lowering of thyroid hormone levels during ATD treatment.

[Application of multimode MRI in prediction of nuclear grade of clear cell renal cell carcinoma].

Objective: To investigate the predictive value of multimode MRI features for nuclear grade of clear cell renal cell carcinoma (ccRCC). Methods: From January 2016 to October 2017, 381 patients (387 tumors) with ccRCC proven by pathology in Chinese PLA General Hospital First Medical Center were enrolled (male 293, female 88, age 24-87 years old). The clinical and imaging data of these patients were retrospectively analyzed, including clinical information (gender, age, BMI, smoke, hypertension) and preoperative renal MRI. Pre-and post-contrast MRI features were subjectively scored. The largest diameter of each lesion was measured. Two-sample t-test,Chi-squared test and binuary Logistic regression analysis were used to evaluate the predictive efficacy of clinical and MRI data. Results: According to WHO/ISUP nuclear grade system,all ccRCCs (n=387) were divided into low grade (n=322) and high grade group (n=65). Between two groups, there were significant differences in age and diameter((54±12) vs (59±10) years old, P=0.001; (4.1±2.2) vs (6.2±3.0) cm, P<0.01). In MRI scores,there were significant differences in scores of pseudocapsule, shape and margin,hemorrhage,enhancement degree,cystic-solid,intratumoral vessel,peritumoral vessel, renal sinus invasion, vein thrombosis, lymphadenopathy, necrosis, perinephric invasion and metastasis, DWI signal intensity between high grade group and low grade group (all P<0.01). Binuary Logistic regression analysis showed that shape and margin, enhancement degree and DWI signal intensity were independent predictors for high grade ccRCC (OR=0.181, 95%CI 0.049-0.666; OR=0.393, 95%CI 0.182-0.846; OR=0.336, 95%CI 0.155-0.728). A nomogram model for predicting the risk of high grade ccRCC was constructed. Conclusions: Multimode MRI features can differentiate low grade and high grade ccRCC. The nomogram developed in this study might aid urologist in the pre-operative prediction of nuclear grade of ccRCC,which might contribute to developing treatment strategy.

[Experts consensus on the management of delirium in critically ill patients].

To establish the experts consensus on the management of delirium in critically ill patients. A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group. Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 36 experts to reassess all the statements. (1) Delirium is not only a mental change, but also a clinical syndrome with multiple pathophysiological changes. (2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function. (3) Pain is a common cause of delirium in critically ill patients. Analgesia can reduce the occurrence and development of delirium. (4) Anxiety or depression are important factors for delirium in critically ill patients. (5) The correlation between sedative and analgesic drugs and delirium is uncertain. (6) Pay attention to the relationship between delirium and withdrawal reactions. (7) Pay attention to the relationship between delirium and drug dependence/withdrawal reactions. (8) Sleep disruption can induce delirium. (9) We should be vigilant against potential risk factors for persistent or recurrent delirium. (10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases, and can also be alleviated with the improvement of primary diseases. (11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis. (12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium, especially subclinical delirium. (13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium. (14) Daily assessment is helpful for early detection of delirium. (15) Hopoactive delirium and mixed delirium are common and should be emphasized. (16) Delirium may be accompanied by changes in electroencephalogram. Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant. (17) Pay attention to differential diagnosis of delirium and dementia/depression. (18) Pay attention to the role of rapid delirium screening method in delirium management. (19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium. (20) The key to the management of delirium is etiological treatment. (21) Improving environmental factors and making patient comfort can help reduce delirium. (22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium. (23) Communication with patients should be emphasized and strengthened. Family members participation can help reduce the incidence of delirium and promote the recovery of delirium. (24) Pay attention to the role of sleep management in the prevention and treatment of delirium. (25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium. (26) When using antipsychotics to treat delirium, we should be alert to its effect on the heart rhythm. (27) Delirium management should pay attention to brain functional exercise. (28) Compared with non-critically illness related delirium, the relief of critically illness related delirium will not accomplished at one stroke. (29) Multiple management strategies such as ABCDEF, eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients. (30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment. (31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management. Consensus can promote delirium management in critically ill patients, optimize analgesia and sedation therapy, and even affect prognosis.

[Clinical efficacy of rivaroxaban in prevention and treatment of postoperative deep vein thrombosis for severe traumatic brain injury].

Objective: To explore the clinical efficacy of rivaroxaban in the prevention and treatment of postoperative deep vein thrombosis (DVT) for severe traumatic brain injury (sTBI). Methods: Patients with sTBI who met the inclusion criteria were enrolled in this study, including 119 males (75.8%) and 38 females (24.2%), aged (38.75 ± 11.98) years old. DVT was prevented and treated according to the DVT screening and anticoagulation regimen. Intermittent venous compression was used on all of the patients to prevent DVT, and D-dimer dynamic monitoring and regular ultrasound were performed to screen for DVT. For patients with stable intracranial hemorrhage, rivaroxaban was used when the D-dimer was declining continuously and high risks exist at the same time, or the DVT was diagnosed. Drug withdrawal was performed according to the regimen. The clinical information, D-dimer dynamic changes, rivaroxaban application, DVT, and bleeding complications were analyzed retrospectively. Results: None of the patients with continuously declining D-dimer was diagnosed with DVT according to the ultrasound examination. Of the 45 patients without progressively declining D-dimer, 43 cases were diagnosed with DVT. Rivaroxaban was used in 47 cases (29.9%) to prevent DVT and 43 cases (27.4%) to treat DVT, and the medication time was (16.3±6.5) and (49.3 ± 9.9) days, respectively. None was diagnosed with DVT after prophylactic administration, and 1 case relapsed after therapeutic administration. During the 6-months follow-up after injury, hematuria occurred in 3 cases, tracheotomy errhysis in 1 case and hemorrhoids bleeding in 1 case. Symptomatic pulmonary embolism, intracranial hemorrhage and fatal bleeding did not occur in any of the cases. Conclusions: The application of rivaroxaban is safe and effective in preventing and treating the postoperative DVT.

[Clinical efficacy of acute intraoperative encephalocele prevention strategy for severe traumatic brain injury].

Objective: To explore the clinical efficacy of prevention strategy for acute intraoperative encephalocele of patients with severe traumatic brain injury (sTBI). Methods: A total of 173 patients with sTBI, who treated in Emergency Neurosurgery Department of Shandong University Qilu Hospital from January, 2011 to September, 2015 were collected and divided into research group and control group, according to their therapeutic strategy.The clinical data during hospitalization and prognosis 1 year after injury was analyzed retrospectively to clarify the effect of acute encephalocele prevention strategy. Results: There were no statistically significant differences in sex, age, preoperative Glasgow coma scale score and imaging type of lesion between patients from the two groups.The highest intraoperative intracranial pressure in the research group and control group were (35.71±4.13) mmHg and(34.85±3.81) mmHg, respectively.The acute encephalocele incidence of the research group (7 cases, 6.5%) was significantly lower than that of the control group (13 cases, 19.7%) (P<0.01). Subgroup analysis showed that the incidence of acute encephalocele in patients with only unilateral lesions was low (1.3%), while higher (19.4%) in patients with both unilateral lesions and other secondary lesions or diffuse brain swelling.The prognosis of the patients was evaluated by Glasgow Outcome Scale according to the follow-up 1 year after injury, and it was suggested that the percentage of patients with good outcome in the research group (62 cases, 57.9%) was remarkably higher than that in the control group (26 cases, 39.4%) (P=0.018). Conclusions: For sTBI patients with high risk of acute encephalocele, prevention strategy was found to be able to retard the progression of delayed hematoma and diffuse brain swelling, prevent the acute encephalocele during operation, and then significantly improve the prognosis.

Detection of cancer stem cells from the C6 glioma cell line.

Various malignant cancers have been found to contain a sub-population of stem cell-like tumour cells, or cancer stem cells (CSCs), however, culture methods for CSCs and the size of the fraction of CSCs in C6, which is a commonly used glioma cell line, remain controversial. In this study, we demonstrated that the C6 cell line contains a fraction of tumour cells that can form tumour spheres in a simplified serum-free neural stem cell medium and express CD133 and nestin, which are widely-used markers for brain CSCs. Immunohistochemistry and immunofluorescence confirmed the existence of CSCs both in the C6 cell line and C6 xenografts. Flow cytometry demonstrated that 4.02% of cells in the C6 cell line and 4.21% in the C6 xenografts presented as CSCs. These results confirm the fraction of CSCs in the C6 cell line and provide a simple and effective method for isolation of CSCs to study the initiation and progression of human glioma and, possibly, other malignant tumours.

[Pharmacological intervention in experimental multiple organ failure in rats].

This paper presents a primary study of the treatment of experimental multiple system organ failure (MSOF) in rats. The rats were pretreated with xanthine oxidase inhibitor allopurinol, the energy metabolism regulator fructose-1,6-diphosphate (FDP) and purified Chinese herbal medicine polydatin. The incidence of MSOF decreased from 71.4% in the untreated group to 35.7%, 47.1% and 16.7% in treated groups, respectively, while the mean survival time was prolonged to 38.5h, 30.2h and 41.7h in treated groups, respectively, as compared with 26.4h in the untreated group. In addition to the known antioxidant effect of the allopurinol, this study also suggests that FDP and polydatin enhance the capacity of antioxidtion.