[Expert consensus on the application of critical care ultrasonography in invasive procedures].

The evolution of critical care medicine is inextricably linked to the development of critical care procedures. These procedures not only facilitate diagnosis and treatment of critically ill patients, but also provide valuable insights into disease pathophysiology. While critical care interventions offer undeniable benefits, the potential for iatrogenic complications necessitates careful consideration. The recent surge in critical care ultrasound (US) utilization is a testament to its unique advantages: non-invasiveness, real-time bedside availability, direct visualization of internal structures, elimination of ionizing radiation exposure, repeatability, and relative ease of learning. Recognizing the need to optimize procedures and minimize complications, critical care utrasound study group of Beijing critical care ultrasound research assocition convened a panel of critical care experts to generate this consensus statement. This document serves as a guide for healthcare providers, aiming to ensure patient safety and best practices in critical care.

[Immunotherapy advances for lung cancer combined with chronic obstructive pulmonary disease].

Lung cancer is a major public health problem worldwide, with high rates of morbidity and mortality. It often coexists with chronic obstructive pulmonary disease (COPD), the diagnosis and management of which often receives insufficient attention. In particular, the presence of COPD has significant implications for the clinical management of lung cancer patients. This review systematically assesses the influence of COPD on the efficacy of immunotherapy and the occurrence of immune-related adverse events in patients with lung cancer, identifies existing challenges and proposes avenues for future research in this field.

Olfactory stimulation may modulate the sensation of nasal patency.

BACKGROUND: The sensation of nasal patency can be induced by inhaling menthol, which predominantly produces trigeminal stimulation. It remains unclear whether olfactory stimulation can also induce or modulate the sensation of nasal patency. METHODOLOGY: A total of 118 participants (normosmia: n=67, olfactory dysfunction: n=51) were exposed to four odors in a randomized order: 1) phenylethanol (PEA), 2) menthol, 3) a mixture of PEA and menthol, 4) nearly odorless propylene glycol. The odors were presented by nasal clips. After the nasal clip had been removed, the participants rated relative nasal patency (RNP) from - 50 to +50, and their peak nasal inspiratory flow (PNIF) was measured. Repeated measures analysis of variance was used to examine the difference of RNP and PNIF among the four conditions and the influence of olfactory function. RESULTS: The RNPs, other than PNIFs, differed between the four conditions. Menthol induced the highest RNP, followed by the mixed solution, PEA and the odorless condition. Normosmic participants, but not those with olfactory dysfunction, responded to PEA significantly higher than odorless condition with regard to RNP. The correlation analysis showed that the better the subjective or measured olfactory performance, the greater the PEA-induced sensation of nasal patency. CONCLUSIONS: A specific olfactory stimulant that selectively induces olfactory perception can also evoke and modulate the sensation of nasal patency. Hence, patients might benefit from exposing themselves to odors in order to relieve the annoying nasal obstruction.

Menstrual cycle-modulated intrinsic connectivity enhances olfactory performance during periovulatory period.

BACKGROUND: Olfactory capacity increases during the period of ovulation, perhaps as an adjunct to mate selection; however, researchers have yet to elucidate the neural underpinning of menstrual cycle-dependent variations in olfactory performance. METHODOLOGY: A cohort of healthy volunteers (n = 88, grand cohort) underwent testing for gonadal hormone levels and resting-state functional magnetic resonance imaging with a focus on intrinsic functional connectivity (FC) in the olfactory network based on a priori seeds (piriform cortex and orbitofrontal cortex) during the periovulatory (POV) and menstrual (MEN) phases. A subcohort (n = 20, olfaction cohort) returned to the lab to undergo testing of olfactory performance during the POV and MEN phases of a subsequent menstrual cycle. RESULTS: Olfactory performance and FC were both stronger in the periovulatory phase than in the menstrual phase. Enhanced FC was observed in the network targeting the cerebellum in both the grand and olfaction cohorts, while enhanced FC was observed in the middle temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex, and postcentral gyrus in the grand cohort. Periovulatory progesterone levels in the grand cohort were positively correlated with FC in the network targeting the insula and paracentral lobule. CONCLUSIONS: Our analysis revealed that superior olfactory function in the periovulatory period is associated with enhanced intrinsic connectivity in the olfactory network. These findings can be appreciated in the context of evolutionary biology.

[Analysis and treatment workflow of modified seven-step approach for acute respiratory and circulatory disorders].

Acute respiratory and circulatory disorders are the most common critical syndromes, the essence of which is damage to the organs/systems of the heart and lungs. These comprise the essential manifestation of disease and injury progression to the severe stage. Its development involves the following components: individual specificity, primary disease strike, dysregulation of the host's response, and systemic disorders. Admission for acute respiratory and circulatory disorders is a clinical challenge. Based on a previously proposed flow, a critical care ultrasound-based stepwise approach (PIEPEAR) as a standard procedure to manage patients with acute cardiorespiratory compromise and practical experience in recent years, a modified seven-step analysis and treatment process has been developed to help guide clinicians with rational thinking and standardized treatment when faced with acute respiratory and circulatory disorders. The process consists of seven steps: problem-based clinical analysis, intentional information acquisition, evaluation of core disorder based on critical care ultrasound, pathophysiology and host response phenotype identification, etiology diagnosis, act treatment through pathophysiology-host response and etiology, and re-check. The modified seven-step approach is guided by a "modular analysis" style of thinking and visual monitoring. This approach can strengthen the identification of clinical problems and facilitate a three-in-one analysis. It focuses on pathophysiological disorders, body reactions, and primary causes to more accurately understand the condition's key points, and make treatment more straight forward, to finally achieve the aim of "comprehensive cognition and refined treatment".

[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.

A Novel Tumor Staging System Incorporating Tumor Regression Grade (TRG) With Lymph Node Status (ypN-Category) Results in Better Prognostication Than ypTNM Stage Groups After Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aims at constructing a staging system incorporating tumor regression grade and ypN-category (TRG-N) in patients with neoadjuvant therapy before esophagectomy. It is hypothesized that this would prognosticate better than the current American Joint Committee on Cancer (AJCC) postneoadjuvant therapy (ypTNM) stage groups. BACKGROUND: Conventional pathological T-category is defined by the depth of invasion, and may lose prognostic relevance after neoadjuvant therapy. TRG defines treatment response by the degree of tumor regression, and when combined with ypN-category may be more prognostic than AJCC postneoadjuvant therapy (ypTNM) stage groups. METHODS: A training cohort of 210 patients with esophageal squamous cell carcinoma and who had had neoadjuvant therapy before esophagectomy were studied. A validation cohort comprised 107 patients from another hospital. Resected esophagi were assessed by ypT-category and TRG, the latter assigned according to the Becker 4-tier system. These categories were grouped with ypN-category into a TRG-N system. Patients' survival was compared between the current AJCC postneoadjuvant therapy (ypTNM) stage groups and this TRG-N system. RESULTS: In the training cohort, 5-year survival rates according to ypTNM stage I, II, IIIA, IIIB, and IVA were 53%, 39.4%, 47%, 18.3%, and 0%, respectively. For TRG-N stages I, II, III, and IV, the respective figures were 59.6%, 43.5%, 23.8%, and 15.6%. TRG-N stage showed better fit in survival than ypTNM stage groups, indicated by lower Akaike Information Criteria (AIC) and Bayesian Information Criterion values. Similar results were found in the validation cohort. Multivariate analysis showed that TRG-N stage ( P =0.02), age ( P =0.006), and sex ( P =0.005) were independent prognostic factors. CONCLUSION: TRG-N stage shows better prognostication than the AJCC postneoadjuvant therapy (ypTNM) stage groups.

Profiled polyethylene terephthalate filaments that incorporate collagen and calcium phosphate enhance ligamentisation and bone formation.

Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.

[The quality control standards and principles of the application and training of critical ultrasonography].

Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians' heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.

Toll-like receptor signalling associated with immunomodulation of umbilical cord-derived mesenchymal stem cells in mice with systemic lupus erythematosus.

With potent immunomodulatory activities, mesenchymal stem cells (MSCs) have the potential to be a beneficial treatment option for diseases with aberrant immune responses such as systemic lupus erythematosus (SLE). However, the underlying mechanisms remain largely unknown. Here, we used NZBWF1 mice as a SLE animal model to examine immunomodulation of MSCs as well as to assess the role of Toll-like receptor signalling in this circumstance. We found that mice receiving MSCs had a significant decrease in severity of proteinuria at 20 and 22 weeks of age (p = 0.009 and p = 0.022, respectively). Serum anti-dsDNA levels were significantly lower compared with the control group (p = 0.016 and p = 0.036, respectively). C3 and C4 levels were significantly higher at 22 weeks of age (p = 0.046 and p = 0.016, respectively). Altered expression of inflammation-associated cytokine profiles in the serum was also noted in mice receiving MSCs. Down-regulation of myeloid differentiation factor 88 (MyD88)-nuclear factor-κB (NF-κB) signalling in the liver was demonstrated by quantitative polymerase chain reaction, ELISA and Western blotting. In addition to demonstrating the beneficial effects of MSC treatment in NZBWF1 mice, our study provided the first evidence for the association of MyD88-NF-κB signalling and MSC-mediated immunomodulation in this disease.

MicroRNA-142-3p suppresses cell proliferation and migration in bladder cancer via Rac1.

Expression of microRNA(miR)-142-3p has been implicated to be associated with several cancers, whereas its function in bladder cancer (BC) remains unknown. The present study aimed to explore the correlation between the expression of miR-142-3p and the proliferation, migration and invasion of bladder cancer cells by activating Rac1. qRT-PCR was used to measure the expression of miR-142- 3p in bladder cancer tissues and cell lines. RNA transfection was used to silence and accelerate the expression of miR-142-3p in bladder cancer cells. CCK-8 and trans-well assays were used to detect the proliferation, migration and invasion of cells before and after RNA transfection. The direct interaction between Rac1 and miR-142-3p was demonstrated by a dual luciferase reporter assay. qRT-PCR and Western blot assays were used to detect the expression changes in Rac1 before and after transfection. The results showed that miR-142-3p in bladder cancer tissues was significantly lower than that in adjacent tissues and lower than that in HT1376 and T-24 cells but higher than that in T5637 and BIU- 87 cells. Additionally, upregulating miR-142-3p expression not only inhibits the proliferation of SV-HUC-1 and BIU-87 cells but also inhibits migration and invasion, and downregulating miR-142-3p expression showed the opposite results. The expression of Rac1 was promoted after stimulating miR- 142-3p expression, but was inhibited after silencing miR-142-3p expression. In conclusion, miR-142-3p affects the proliferation, migration and invasion of bladder cancer cells by regulating Rac1.

A standardized approach for the thoracic dissection in robotic-assisted minimally invasive esophagectomy (RAMIE).

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being adopted as the preferred surgical treatment for esophageal cancer, as it is superior to open esophagectomy and a good alternative to conventional minimally invasive esophagectomy. This paper addresses the technical details of the thoracoscopic phase of RAMIE, including the operating room set-up, patient positioning, port placement, and surgical steps.

A three-generation family cluster with COVID-19 infection: should quarantine be prolonged?

OBJECTIVES: Families are a transmission route for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of the close contact. Monitoring of the viral load will be a valuable method to reduce the optimal number of quarantine days, especially in presymptomatic and symptomatic carriers of their households. The traditional three-generation families living together are seen frequently in East Asia, including in Taiwan. STUDY DESIGN: We report on a family cluster with six individuals infected with coronavirus disease in Taiwan. METHODS: The current public policy in Taiwan is quarantine for at least 14 days, based on the incubation period, or until the patient has tested negative three days in a row using the SARS-CoV-2 reverse transcription polymerase chain reaction. Details on the onset date of clinical symptoms, throat swab conversion, and course of disease were collected from medical records retrospectively. RESULTS: In the household of this three-generation Taiwanese family, the infection rate was 60%. The ratio of males to females was 4:2, and the age range was 11-85 years. The prevalence of asymptomatic disease was 33.3% (2/6). The longest throat swab conversion time was 37 days, and the estimated course of disease from symptoms to first conversion of throat swab was 59 days. CONCLUSIONS: Large families, including three-generation families in a single dwelling, should be monitored when the index case is found. Presymptomatic and symptomatic family members could be quarantined for an appropriate duration which, in our experience, is 2 months.

[Recommendations for the treatment of severe coronavirus disease 2019 based on critical care ultrasound].

Severe patients with coronaviras disease 2019 (COVID-19) are characterized by persistent lung damage, causing respiratory failure, secondary circulatory changes and multiple organ dysfunction after virus invasion. Because of its dynamic, real-time, non-invasive, repeatable and other advantages, critical ultrasonography can be widely used in the diagnosis, assessment and guidance of treatment for severe patients. Based on the recommendations of critical care experts from all over the country who fight against the epidemic in Wuhan, this article summarizes the guidelines for the treatment of COVID-19 based on critical ultrasonography, hoping to provide help for the treatment of severe patients. The recommendations mainly cover the following aspects: (1) lung ultrasound in patients with COVID-19 is mainly manifested by thickened and irregular pleural lines, different types of B-lines, shred signs, and other consolidation like dynamic air bronchogram; (2) Echocardiography may show right heart dysfunction, diffuse cardiac function enhancement, stress cardiomyopathy, diffuse cardiac depression and other multiple abnormalities; (3) Critical ultrasonography helps with initiating early treatment in the suspect patient, screening confirmed patients after intensive care unit admission, early assessment of sudden critical events, rapid grading assessment and treatment based on it; (4) Critical ultrasonography helps to quickly screen for the etiology of respiratory failure in patients with COVID-19, make oxygen therapeutic strategy, guide the implementation of lung protective ventilation, graded management and precise off-ventilator; (5) Critical ultrasonography is helpful for assessing the circulatory status of patients with COVID-19, finding chronic cardiopulmonary diseases and guiding extracorporeal membrane oxygenation management; (6) Critical ultrasonography contributes to the management of organs besides based on cardiopulmonary oxygen transport; (7) Critical ultrasonography can help to improve the success of operation; (8) Critical ultrasonography can help to improve the safety and quality of nursing; (9) When performing critical ultrasonography for patients with COVID-19, it needs to implement three-level protection standard, pay attention to disinfect the machine and strictly obey the rules from nosocomial infection. (10) Telemedicine and artificial intelligence centered on critical ultrasonography may help to improve the efficiency of treatment for the patients with COVID-19. In the face of the global spread of the epidemic, all we can do is to share experience, build a defense line, We hope this recommendations can help COVID-19 patients therapy.

Do dysplastic proximal resection margins predict the risk of anastomotic recurrence and overall survival in patients with esophageal squamous cell carcinoma?

Positive proximal resection margins are strongly associated with anastomotic recurrence in esophageal cancer. However, the prognostic significance of dysplastic proximal resection margins remains unclear. The aim of this study is to investigate whether the dysplastic proximal resection margin can predict anastomotic recurrence and overall survival in patients with esophageal squamous cell carcinoma. Between 2000 and 2014, patients with esophageal squamous cell carcinoma who received a nonpalliative resection and survived the perioperative period were included. Two expert pathologists independently reviewed the proximal resection margin status, which was classified as negative, dysplastic, or positive. The kappa statistic was used to test interobserver reliability. Anastomotic recurrence and overall survival served as the main outcome measures. The study cohort consisted of 469 patients (445 males and 27 females). There was an excellent interobserver agreement for negative (kappa = 0.88), dysplastic (kappa = 0.88), and positive (kappa = 1) proximal resection margins-which were identified in 418 (89.1%), 37 (7.9%), and 14 (3.0%) patients, respectively. After a median follow-up of 21.6 months, 30 (6.4%) patients developed an anastomotic recurrence. Compared with patients with negative proximal resection margins (24/418, 5.7%), the occurrence of anastomotic recurrence was more commonly observed in those with positive proximal resection margins (3/14, 21.4%, P = 0.017) but not in those with dysplastic proximal resection margins (3/37, 8.1%, P = 0.56). Multivariable Cox regression analysis identified positive proximal resection margins (hazard ratio: 5.93, P = 0.010) and advanced clinical stage (hazard ratio: 12.04, P = 0.023) as independent risk factors for anastomotic recurrence. Dysplastic proximal resection margins were not retained in the model as an independent predictor (hazard ratio: 1.38, P = 0.602). The 5-year overall survival rates of patients with negative (38.2%) and dysplastic margins (27.0%) were similar (P = 0.814), and significantly higher than that observed in those with positive proximal resection margins (9.5%, P = 0.015). In conclusion, dysplastic proximal resection margins can be identified in at least 7.9% of patients with esophageal squamous cell carcinoma, but neither they are associated with an increased risk of anastomotic recurrence nor they portend a poor overall survival.

[A Chinese consensus statement on the clinical application of transesophageal echocardiography for critical care (2019)].

Transesophageal echocardiography(TEE) is valuable in intensive care unit (ICU) because its application meets the requirements of diagnosis and treatment of critically ill patients.However, the current application has not fully adapted to the specialty of critical care. TEE could be more valuablein ICU when used with a new way that under the guidance of the theory of critical care and embedded into the treatment workflow. We have expanded and improved the application of traditional TEE and integrated the concept of critical care, established the concept of transesophageal echocardiography for critical care (TEECC). Chinese Critical Ultrasound Study Group (CCUSG) organized experts in the area to form the consensus based the previous studiesand the long term practice of critical care ultrasound and TEE, aiming at clarifying the nature and characteristics of TEECC, promoting the rational and standardized clinical application and the coming researches.The consensus of Chinese experts on clinical application of TEECC (2019) were 33 in total, of whichthe main items were as follows: (1) TEECC is a significant means, which is expanded and improved from the traditional transesophageal echocardiography according to characteristics of critically ill patients and is applied in ICU based on critically clinical scenarios and requirements by the critical care physician, to promote visualized, refined and precisely management of critically ill patients.(2) TEE possesses distinctive superiority in implementation in ICU. It has characteristics of images with good quality, operations with good stability and low-dependent of operators, monitoring with continuity, and visualization with all-dimensional and detail of heart and blood vessels.(3)As a means of refined monitoring that could resulted in precise diagnosis and treatment, TEECC expands the dimension of intensive monitoring and improves the performance of critical care. (4) Indications of TEECC application include clinical etiological searching and invasive procedures guiding when it acted as a traditional role; and also refined hemodynamic monitoring based on critical care rationale and over-all management under specific critical clinical scenarios. (5) TEE and TTE assessments are complementary; they are not alternative. Integrated assessment of TTE and TEE is required under many critical clinical scenarios.(6) TEE should be a necessary configuration in ICU. (7) All-round and significant information regarding to the mechanism of acute circulatory disorders can be provided by TEECC; it is a non-substitutable means of identifying the causes of shock under some special clinical scenarios. (8) Focal extracardiac hematoma can be accurately and rapidly detected by TEE in patients with open-thoracic cardiac surgery or severe chest trauma when highly suspected pericardial tamponade.(9) The priority of pathophysiologic mechanism of septic shock can be rapidly and accurately identified by TEE; even if its pathophysiological changes are complex, including hypovolemia and/or vasospasm and/or left and right heart dysfunction. (10) Causes of hemodynamic disorders can be rapidly and qualitatively evaluated so that the orientation of treatment can be clarified by TEECC. (11) A full range of quantitative indicators for refined hemodynamic management in critically ill patients can be provided by TEECC. (12) TEECC helps to accurately assess volume status and predict fluid responsiveness.(13) TEECC is specially suitable for accurate quantitative assessment of cardiac function.(14) Mini TEE provides long-term continuous hemodynamic monitoring. (15) Standard views are easy to be acquired by TEECC, which is a premise for accurate and repeatable measurements, and a guarantee for assessment of effect and risk of therapy. (16) Compared with invasive hemodynamic monitoring, TEECC is minimally invasive, with low infection risk and high safety.(17) In patients with acute cor pulmonale (ACP) under condition of right ventricular dysfunction and low cardiac output, TEECC is a key tool for assessment. (18) TEECC should be implemented actively when suspicious of left to right shunt in critically ill patients who occurred hypotension that hard to explain the cause. (19) TEECC should be implemented actively when suspicious of right to left shunt in critically ill patients who occurred hypoxemia that hard to explain the cause. (20) TEECC is preferred in hemodynamics monitoring under prone position of ventilated patients.(21) TEECC is an imperative means to achieve over-all management of extracorporeal membrane oxygenation (ECMO) therapy, especially for all-round hemodynamic monitoring. (22) Three basic views is recommended to be used to simplify TEE assessment during cardiac arrest so that reversible causes could be identified, and resuscitation could be guided. (23) The flow related echodynamic evaluation (TEECC-FREE) workflow is preferred in refined hemodynamics monitoring and therapy. (24) Simple workflow of TEECC could be implemented in special critical clinical scenarios. (25) Application of TEECC is highly secure; however, impairments of procedure should also be alert by operators. (26) Pitfalls in application of TEE should be paid attention to by the critical care physician. (27) Timely and rationally application of TEECC is in favor of diagnosis and treatment of critically ill patients and may improve the prognosis.

[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.

Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.

Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. Results: A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials.gov (NCT 01287585).

[Technical specification for clinical application of critical ultrasonography].

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound, the examiner and interpreter of the image are critical care medicine physicians. The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes. With the idea of critical care medicine as the soul, it can integrate the above information and clinical information, bedside real-time diagnosis and titration treatment, and evaluate the therapeutic effect so as to improve the outcome. CUS is a traditional technique which is applied as a new application method. The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept, implementation and application of CUS. It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure. At the same time, the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications, and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS. Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group, based on the rich experience of clinical practice in critical care and research, combined with the essence of CUS, to learn the traditional ultrasonic essence, established the clinical application technical specifications of CUS, including in five parts: basic view and relevant indicators to obtain in CUS; basic norms for viscera organ assessment and special assessment; standardized processes and systematic inspection programs; examples of CUS applications; CUS training and the application of qualification certification. The establishment of applied technology standard is helpful for standardized training and clinical correct implementation. It is helpful for clinical evaluation and correct guidance treatment, and is also helpful for quality control and continuous improvement of CUS application.