[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.

[Clinicopathological features of primary mucosal CD30-positive T-cell lymphoproliferative disorders].

Objective: To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30+TLPD). Methods: Eight cases of pmCD30+TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results: There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed "kidney-shaped", "embryonic" and "horseshoe-shaped" cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia. Conclusions: pmCD30+TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30+TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.

[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.

[Current satus and future direction of neuromonitoring in patients on extracorporeal membrane oxygenation].

Neurological complications significantly affect the short-and long-term outcomes of patients with extracorporeal membrane oxygenation (ECMO). With the increasing application of ECMO, more and more attention has been paid to the neuromonitoring in ECMO patients. Although many neuromonitoring approaches have already been used clinically, the sensitivity and specificity utilizing one single neuromonitoring assessment to predict brain injury is still insufficient. Therefore, multidisciplinary experts in critical care medicine and extracorporeal life support organization advocate that multimodal monitoring (MMM) should be applied to improve the sensitivity and specificity of monitoring the occurrence of acute brain injury in patients with ECMO. With timely and appropriate intervention, the prognosis of patients with ECMO may be improved. However, there is still a lack of standardized implementation procedures for MMM, which needs further efforts. With continuous verification and improvement in multi-clinical centers, the standardized MMM procedures could be transformed into correct treatment decisions, thus to improve the outcomes of patients with ECMO.

[Prenatal diagnosis and clinical outcomes of 297 fetuses with conotruncal defects].

Objective: To analyze the prenatal diagnosis results and pregnancy outcomes of conotruncal defects (CTD) fetuses, and to explore the correlation between the CTD and chromosome diseases. Methods: A total of 297 cases of invasive prenatal diagnosis and chromosome analysis were collected at the Prenatal Diagnosis Center of Guangzhou Women and Children's Medical Center due to CTD from January 1st, 2011 to December 31th, 2019. According to ultrasonic diagnosis, CTD fetuses were divided into 6 subtypes: tetralogy of Fallot (109 cases), pulmonary atresia (30 cases), transposition of the great arteries (77 cases), double outlet right ventricle (53 cases), truncus arteriosus (14 cases) and interrupted aortic arch (14 cases). According to whether they were combined with intracardiac or extracardiac abnormalities, they were divided into simple group (134 cases), combined with other intracardiac abnormalities group (86 cases), combined with extracardiac abnormalities group (20 cases), combined with intracardiac and extracardiac abnormalities group (37 cases) and only combined with ultrasound soft marker group (20 cases), the last 4 groups were referred as non-simple types. The chromosome test results and pregnancy outcomes of each type and group were analyzed retrospectively. Results: Among the 297 CTD fetuses, the chromosome abnormality rate was 17.5% (52/297). There were 21 cases of abnormal chromosome number, 28 cases of pathogenetic copy number variantions and 3 cases of mosaics. All the 19 cases of micropathogenic fragments smaller than 5 Mb were detected by chromosomal microarray analysis (CMA). Among all the subtypes of CTD, the chromosomal abnormality rate of truncus arteriosus was the highest, at 7/14; while the rate of transposition of the great arteries was the lowest, at 5.2% (4/77). There were significant differences in the rate of chromosomal abnormalities between simple and non-simple types [10.4% (14/134) vs 23.3% (38/163); χ²=8.428, P=0.004]. In each group, the chromosomal abnormality rate was the highest in the combined with intracardiac and extracardiac abnormalities group, at 37.8% (14/37), and the lowest in the simple group, at 10.4% (14/134). There was no significant difference in the rate of chromosomal abnormalities in all subtypes of simple group (all P>0.05). Among 112 cases of live birth, 1 case was 22q11.2 microdeletion syndrome, 5 cases of postnatal clinical diagnosis and prenatal ultrasound diagnosis were not completely consistent, 5 cases died after birth. Conclusions: The incidence of chromosomal abnormalities is high in fetuses with CTD. CTD fetuses with concurrent extrapardiac malformations are more likely to incorporate chromosomal abnormalities. CMA technology could be used as a first-line genetic detection method for CTD. After excluding chromosomal abnormalities, most of the children with CTD have good prognosis.

[Clinicopathological features of angioimmunoblastic T-cell lymphoma pattern â ].

Objective: To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma pattern Ⅰ (AITL Pattern Ⅰ). Methods: The clinicopathological data of 11 AITL Pattern Ⅰ cases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University (10 cases) and Beijing Lu Daopei Hospital (1 cases) from January 2019 to October 2021 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of the tumor cells were tested, and clinicopathological features of cases were analyzed. Results: Among the 11 AITL Pattern Ⅰ cases, the male to female ratio was 1.2∶1.0. The median age was 59 years (range 47-78 years). Seven cases had B symptoms, while eleven cases presented with systemic lymphadenopathy. According to Ann Arbor system staging, two cases were classified as stage Ⅰ-Ⅱ, and 9 cases as stage Ⅲ-Ⅳ. Hepatosplenomegaly was present in two cases (2/11), three cases (3/11) had skin rash and pruritus, and two cases (2/11) had pleural effusion. Previously, 6 cases (6/11) were diagnosed as reactive hyperplasia, 1 case (1/11) as EBV-associated lymphoproliferative disorder, and 4 cases (4/11) as hyperplasia of lymphoid tissue, which was unable to exclude lymphoma. Histologically, all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers. The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases. Mantle zones completely disappeared in 4 cases. The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm. In 2 cases, the clear cells were located between the germinal centers and the thin residual mantle cell layers, showing a circular growth pattern. The cells were medium in size, with irregular karyotype, coarse chromatin and indistinct nucleoli. Immunohistochemically, CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles. There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders. The atypical cells surrounding the follicles expressed CD3 (11/11), CD4 (11/11), PD-1 (11/11), CXCL13 (6/11), ICOS (10/11) and CD10 (7/11). PD-1 staining showed a strong perifollicular pattern, and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region. CXCL13, ICOS and CD10 showed similar distribution patterns. EBV-encoded small RNA probe (EBER) in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region (5-20/HPF) in all cases. T cell receptor gene rearrangement was monoclonal in all cases. Conclusions: Diagnosing AITL Pattern Ⅰ may be challenging and requires comprehensive analysis of clinical manifestations, histological morphology, immunophenotype and gene rearrangement results.

[A preliminary study on the classification and prognosis of microcirculation alterations in patients with septic shock].

Objective: To explore the correlation between different types of microcirculation alterations and the prognosis in patients with septic shock. Methods: This research employed a prospective observational study methodology for selecting subjects with septic shock. Side-stream dark field(SDF) was used to monitor the sublingual microcirculation to determine the total vascular density (TVD), perfused vessel density (PVD), the proportion of perfused vessels (PPV), and the microvascular flow index (MFI), heterogeneity index (HI) indicators. At the bedside, patients with microcirculation disorders were divided into four types: stasis, dilution, heterogeneity, and hyperdynamic. The 30-day survival status after enrollment and hemodynamics parameters were recorded. Results: A total of 64 patients with septic shock were selected in the study, including 18 cases of stasis type, 11 of dilution type, 18 of heterogeneous type, and 17 of hyperdynamic type. There were statistical differences in the mean arterial pressure (MAP) [stasis:(77±9) mmHg (1 mmHg=0.133 kPa), dilution:(80±11) mmHg, heterogeneity: (78±12) mmHg, hyperdynamic:(88±12) mmHg], TVD [ stasis:(10.84±3.01) mm/mm2, dilution:(9.64±1.72) mm/mm2, heterogeneity:(11.39±2.18) mm/mm2, hyperdynamic: (11.87±2.67) mm/mm2 ], PVD [stasis:(5.93±1.94) mm/mm2, dilution:(6.86±1.48) mm/mm2, heterogeneity: (8.31±1.78) mm/mm2, hyperdynamic:(9.68±2.46) mm/mm2], PPV [stasis:52.45 (46.25, 63.33)%, dilution:73.70 (61.50, 75.20)%, heterogeneity: 71.25 (67.95, 77.00)%, hyperdynamic:80.70 (77.25, 86.45)%], MFI(stasis:1.34±0.45, dilution: 1.70±0.38, heterogeneity:1.82±0.28, hyperdynamic:2.25±0.33), and HI [stasis:0.68 (0.51, 1.87), dilution: 0.57 (0.49, 0.64), heterogeneity:0.70 (0.59, 0.91), hyperdynamic: 0.40 (0.37, 0.52)] of the four types of microcirculation alterations. The cumulative survival rates in stasis, dilution, heterogeneity and hyperdynamic types at 30 day were 7/18, 4/11, 10/18 and 14/17, respectively, which in stasis and dilution types was significantly lower than that of hyperdynamic type (χ²=7.221, P=0.007;χ2=6.764, P=0.009). Multivariate Cox regression analysis showed the type of microcirculation alterations (stasis:RR=4.551, 95%CI 1.228-16.864, P=0.023; dilution:RR=4.086, 95%CI 1.011-16.503, P=0.048), acute physiology and chronic health evaluation Ⅱ (RR=1.077, 95%CI 1.006-1.153, P=0.032) were independent prognostic risk factors. Conclusions: Microcirculation alterations are common in patients with septic shock, and it is hard to predict the types of microcirculation alterations with hemodynamics parameters. The prognosis of patients with septic shock is related to the types of microcirculation alterations, suggesting that routine monitoring of microcirculation might be helpful to guide hemodynamic therapy.

[Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury].

OBJECTIVE: To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection. METHODS: Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens. RESULTS: A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05). CONCLUSION: The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

[Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing].

Objective: To evaluate the value of whole exome sequencing (WES) in prenatal clinical application. Methods: A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed. Results: Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results. Conclusions: WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

Heterogeneity of enhancement kinetics in dynamic contrast-enhanced MRI and implication of distant metastasis in invasive breast cancer.

AIM: To investigate the heterogeneity of enhancement kinetics for breast tumour in order to demonstrate the predictive power of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) features for distant metastasis (DM) in invasive breast cancer. MATERIALS AND METHODS: Time-signal intensity curve (TIC) patterns from 128 patients with invasive breast cancer were analysed by a pixel-based DCE-MRI analysis. This MRI technique enabled pixels with varying TIC patterns (persistent, plateau, washout and non-enhancement) to be categorised semi-automatically and the percentage of different TIC patterns in each breast tumour to be calculated. The percentage of TIC patterns was compared between the DM and non-DM groups. DM-free survival was estimated using Kaplan-Meier survival analysis. RESULTS: This study demonstrated a larger percentage of persistent TIC and non-enhancement TIC was associated with DM in invasive breast cancer. The cut-off values of persistent TIC and non-enhancement TIC were 22.5% and 2.5%. Combining TIC patterns and traditional predictors (tumour size and axillary lymph node status) can improve the prediction efficiency. The multivariable model yielded an area under the receiver operating characteristic curve (AUC) of 0.87 with 0.70 sensitivity and 0.87 specificity in leave-one-out cross-validation (LOOCV). These predictors showed significant differences in DM-free survival by Kaplan-Meier analysis. CONCLUSION: This study shows that breast tumours with higher heterogeneity are more likely to metastasise, and pixel-based TIC analysis has utility in predicting distant metastasis of invasive breast cancer.

[A preliminary study on the evaluation of diaphragm function by ultrasound in patients with invasive mechanical ventilation].

Objectives: To study the feasibility of using ultrasound to evaluate diaphragm function in patients with invasive mechanical ventilation. Methods: From March to December 2017, 40 adult patients with acute respiratory distress syndrome who were admitted to the Department of Critical Care Medicine, Xiangya Hospital, Central South University for more than 48 hours were included. Diaphragmatic excursion and thickness of bilateral anterior, middle and posterior parts were measured by ultrasound for 5 consecutive days. Results: (1) Compared with the diaphragmatic excursion of the right [anterior: (11.05±3.04) mm; middle: (12.08±2.71) mm; posterior: (11.51±3.33) mm] and left [anterior: (13.63±7.52) mm; middle: (15.44±7.52) mm; posterior: (14.76±6.93) mm] sides on day 1, the diaphragmatic excursion of the right [anterior: (8.90±3.65) mm; middle: (10.02±4.24) mm; posterior: (10.25±4.38) mm] and left [anterior: (9.82±1.96) mm; middle: (11.60±1.13) mm; posterior: (11.52±1.98) mm] sides decreased significantly on day 3 (P<0.05). Bilateral anterior, middle and posterior diaphragmatic excursion recovered on day 5, and was higher than the baseline levels on day 1, with the left middle and posterior diaphragmatic excursion changing most significantly. (2) Compared with day 1, 2, 3, the thickening fraction of bilateral anterior, middle and posterior diaphragm were significantly decreased on day 4, with the left middle part [day 1: (33.87±14.34)%; day 2: (37.26±13.91)%; day 3: (30.56±14.27)%; day 4: (15.53±5.68)%] and the left posterior part [day 1: (35.50±15.69)%; day 2: (39.84±15.32)%; day 3: (29.06±14.96)%; day 4: (13.30±5.79)%] changing most significantly (P<0.05). The thickening fractions of left anterior, middle and posterior diaphragm recovered on day 5 compared with that on day 4, but still lower than those on day 1 (P<0.05). Conclusions: It is feasible to evaluate the diaphragm function in patients with invasive mechanical ventilation by ultrasound, which can provide guidance for preventing diaphragmatic atrophy and withdrawing from mechanical ventilation.

[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.

[Analysis of special ehealth service for corona virus disease 2019 (COVID-19) pneumonia].

OBJECTIVE: To analyze how governments, hospitals and information technology(IT) companies use Internet technology to provide online health services during the early stage of corona virus disease 2019 (COVID-19) epidemic in January 2020 in China, and then provide suggestions and coping strategies for the later stage and post-epidemic time. METHODS: We searched for information on ehealth services related to the outbreak of COVID-19 in China. The sources of information were mainstream search engines such as Baidu and the popular interactive social platforms such as Webchat. The keywords were "Internet+pneumonia", "Internet clinic", "pneumonia online clinic" and so on. The time of information was from January 20 to February 3, 2020. The key information was extracted and encoded by two persons back-to-back. The coding information included: name of organization provider, launching time, location of provider, service items, user, health workers engaging in the service, and so on. The coded information was entered and analyzed with SPSS 24.0 and Excel. RESULTS: There were totally 57 projects launched by local governments, hospitals and IT companies. Most of them were launched from January 24th to 27th, the hospital and government projects services regionally, especially in eastern provinces. In this study, 90.48% of the enterprises and 100.00% of the hospitals had online fever clinic and consultation services for COVID-19, 66.67% of the enterprises and 37.04% of the hospitals serviced derivative health problems. Only a few projects provided tele-medical consultation. There were individual projects that provided online health management for home quarantine people. Physicians were the main force of various projects. In some hospital projects, there were also nurses, pharmacists and professional technicians to provide featured consultation. CONCLUSION: Ehealth is useful and helpful for the health care system to rapidly cope with health demand during instantaneous and post epidemic time. Regional distribution of ehealth is unbalanced. There are institutional and technical feasibilities for the emergency application of Internet technology. However, community health centers seldom provide ehealth or connect with tertiary hospitals with Internet. Therefore, all kinds of providers within healthcare system should promote emergence ehealth. Tele-medical diagnosis and referral should be developed by local governments during COVID-19. The application of "Internet+medical treatment" in community medical institutions and synergy among various institutions should be promoted.

[Reevaluation of equivocal HER2 status detected by immunohistochemistry according to the 2019 guidelines for HER2 detection].

Objective To understand the effects and clinical significance of the 2019 guidelines for the human epidermal growth factor receptor 2 (HER2) detection. Methods: According to the 2014 guidelines, 548 cases of invasive breast cancer with equivocal HER2 (2+) detected by immunohistochemistry (IHC) in Taizhou Enze Medical Center, Zhejiang Province, China from 2013 to 2019 were selected. The results of IHC and HER2/CEPl7 double-probe were reevaluated and divided into groups according to the 2019 guidelines for the comparative analysis. Results: Among the 548 IHC HER2 (2+) invasive breast cancers, the number of positive, equivocal and negative cases for HER2 were 96 (17.52%), 81 (14.78%) and 371 (67.70%), respectively, according to the 2014 guidelines. However, according to the 2019 guidelines, 10 cases (1.82%) were reclassified as IHC 1+, 2 cases in the group 2 were reclassified as negative, and all the originally equivocal cases in group 4 were reclassified as negative. Finally, the total number of positive and negative cases for HER2 were 94 (17.15%) and 454 (82.85%), respectively. Conclusions: After applying the 2019 guidelines, the number of IHC 2+ cases decreases, and the positive rate for HER2 also decreases slightly due to the reevaluation change in groups 2 and 4, leading to reclassification of the cases that were deemed equivocal according to the 2014 guidelines. In general, the new 2019 guidelines are more reasonable and easier to use.

[The clinical significance of transcranial Doppler in early diagnosis of sepsis-associated encephalopathy].

Objective: To investigate the clinical significance of transcranial Doppler (TCD) in early diagnosis of sepsis-associated encephalopathy(SAE). Methods: Septic patients admitted to the intensive care unit(ICU) were recruited at Xiangya Hospital, Central South University from July 2015 to March 2016. Clinical data and TCD parameters during 24 hours after admission were collected. All patients were screened for delirium using the confusion assessment method for the intensive care unit (CAM-ICU) twice a day. The gold standard of the diagnosis of SAE was positive CAM-ICU evaluation. Patients were divided into SAE group and the non-SAE group. TCD data including systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), pulsatility index (PI) and resistant index (RI) were analyzed to determine the optimal diagnostic cut-off value. Results: A total of 43 patients were enrolled including 12 in SAE group and 31 in non-SAE group. Vm and Vd were lower in SAE group [Vm: (53.50±12.22) cm/s vs. (61.68±9.63) cm/s, P<0.05; Vd: (33.42±10.87) cm/s vs. (43.16±7.84) cm/s, P<0.01] but PI and RI were significant higher in SAE group[PI:(1.16±0.2) vs. (0.90±0.15), P<0.01;RI:(0.65±0.08) vs. (0.56±0.06), P<0.01] than in non-SAE group. The cut-off values of Vs, Vm, Vd, PI and RI for the diagnosis of SAE were 112cm/s, 55.50cm/s, 34.50cm/s, 1.16, 0.65, respectively, with the relevant sensitivities of 19.4%, 83.9%, 93.5%, 58.3%, 58.3% and the specificities of 100.0%, 50.0%, 58.3%, 96.8%, 96.8%, respectively. The diagnostic AUC of Vd, PI and RI were 0.741, 0.808 and 0.808 respectively. Conclusions: The parameter changes of TCD suggest that the pathogenesis of SAE is related to cerebral hypoperfusion, TCD is a helpful method for the early diagnosis of SAE.

[Combining relative alpha variability and electroencephalogram reactivity to predict the prognosis of hypoxic-ischemic encephalopathy in adult patients].

Objective: To evaluate the role of combining relative alpha variability and electroencephalogram (EEG) reactivity to predict the prognosis of hypoxic-ischemic encephalopathy(HIE) in adult patients. Methods: A total of 28 adult patients with HIE admitted to general intensive care unit at Xiangya Hospital in Central South University were enrolled in this observational study from January2016 to April 2017. These patients with body temperature over 35℃ after 72-hour admission could be continuously monitored at least 12 hours byEEG.At the same time,each patient was assessed for EEG reactivity.Then we analyzed the correlation between EEG reactivity, relative alpha variability and clinical prognosis. Results: EEG reactivity was elicited in 15/28 patients, among whom 12 patients had a good outcome. While in the other 13 patients, EEG reactivity was not elicited, among whom only 3 patients had a good outcome. As to the results ofrelative alpha variability,11/13 patients with degree 3-4were of good prognosis; while only 3/15 patients with degree 1-2 were of good prognosis. Glasgow coma scale(GCS), EEG reactivity, and relative alpha variability were correlated with clinical outcome(χ(2)=5.073,9.073,-3.626, respectively,all P<0.05). The sensitivity of GCS, EEG reactivity, and relative alpha variability to predict the poor prognosis were 69.2%, 76.9%, 84.6%, respectively. The specificity were 73.3%, 80.0%, 73.3%, respectively. The consistency rates were 71.4%, 78.6%, 78.6%, respectively. The positive predictive values were 69.2%, 76.9%, 73.3%, respectively. The negative predictive values were 73.3%, 80.0%, 84.6%, respectively. More importantly, the accuracy of the relative alpha variability combined with EEG reactivity for the prediction of poor prognosis was much higher with the positive predictive value of 90.0%,the specificity of 93.3%, the sensitivity of 69.2%, the consistency rate of 82.1%,and the negative predictive values of 77.8%. Conclusions: The combination of relative alpha variability and EEG reactivityis reliable to predict clinical outcome of patients with HIE.

[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.

[Long-term clinical outcome of children and adolescents with Burkitt's lymphoma treated with rituximab combined with modified NHL-BFM-90 regimen].

Objective: To evaluate the efficacy and safety of rituximab combined with the modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt's lymphoma (BL). Methods: A retrospective analysis of 67 untreated childhood and adolescence patients with BL was made. All patients were treated with the modified NHL-BFM-90 protocol with or without rituximab. Results: The 64 patients (95.52%) achieved complete remission (CR), 3 patients (4.48%) partial remission (PR), and the overall response rate (CR+PR) was 100%. 67 patients were followed up for a median of 44 (3-89) months. The 3 and 5-year overall survival (OS) were 92.54% and 88.98%, respectively. The 3 and 5-year progression-free survival (PFS) were all 90.34%. The 5-year OS were 100%,91.7% and 80.0% in low risk, moderate risk and high risk group, respectively, and the difference was statistically significant (P=0.048). Of the 67 patients, 55 patients (82.09%) were treated with rituximab plus chemotherapy. Compared with the 5-year OS and PFS of 74.3% and 78.6% in the chemotherapy group, the 5-year OS and PFS in the rituximab plus chemotherapy group were 95.2% and 95.5%, respectively, and the difference was statistically significant (P value was 0.021, and 0.036, respectively). Major toxicity was myelosuppression and mucositis. No treatment related death was found. Conclusions: Rituximab combined with the modified NHL-BFM-90 protocol was highly effective for children and adolescents with BL, and significantly improved long-term survival.

Polymorphism and Forensic Application Value of 71 Y-SNP Loci in Han Population of Northwest China.

OBJECTIVES: To analyze the polymorphism of 71 SNP loci on Y chromosome in Han population of Northwest China, to assess its forensic application value, and to screen out Y-SNP loci for forensic examination of Han population in East, South, and Northwest China based on the integration of previous research results. METHODS: Multiplex polymerase chain reaction （PCR） and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS） were performed on 71 Y-SNP loci of 202 unrelated Han male individuals in Northwest China. Gene diversity （GD） and haplotype diversity （HD） values were calculated, and then Y-SNP loci of Han population in East, South, and Northwest China were screened with the combination of data from previous research. RESULTS: Among the detected 71 loci, 67 loci were polymorphic in the Northwest Han male population, with GD values 0.010 0-0.502 2. There were 22 and 25 loci with a moderate （0.2≤GD<0.3） and high （GD≥0.3） amount of genetic information, respectively. There were 26 loci for the Han communities in Northwest, South, and East China. CONCLUSIONS: Y-SNP loci are potential in paternity testing and individual identification, as well as the judgement of population distribution and migration.