[Research of progress of mitochondria in the pathogenesis of sepsis].

Sepsis is an organ dysfunction caused by dysregulation of the body's response to infection, with high morbidity and mortality. The pathogenesis of sepsis is still unclear, and there are no specific treatment drugs. As a cell energy supply unit, the dynamic changes of mitochondria are closely related to various diseases. Studies have shown that structure and function of mitochondria are changed in different organs during sepsis. The energy shortage, oxidative stress change, imbalance of fusion and fission, autophagy reduce, biological functions of mitochondria play important roles in sepsis progress, which can provide a research target for the treatment of sepsis.

[Effect of enteral nutritional support on clinical outcomes of patients with sepsis].

OBJECTIVE: To research whether clinical outcomes of patients with sepsis can be improved by higher enteral nutritional support. METHODS: A retrospective cohort method was applied. 145 patients with sepsis who were hospitalized in intensive care unit (ICU) of Peking University Third Hospital from September, 2015 to August, 2021 and met inclusion criteria as well as exclusion criteria were selected, including 79 males and 66 females, the median age was 68 (61, 73). Researchers evaluated whether there was correlation between improved modified nutrition risk in critically ill score (mNUTRIC), daily energy intake and protein supplement of patients and their clinical outcomes through Poisson log-linear regression analysis and Cox regression analysis. RESULTS: The median of mNUTRIC score of 145 hospitalized patients was 6 (3, 10), wherein 70.3% of patients (102 cases) were in high-score group (≥ 5 scores) and 29.7% of patients (43 cases) were in low-score group (< 5 scores); the average of daily protein intake in ICU was about 0.62 (0.43, 0.79) g×kg-1×d-1, and the average of daily energy intake was about 64.4 (48.1, 86.2) kJ×kg-1×d-1. As shown by Cox regression analysis, increase of mNUTRIC score, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) were correlated to growth of in-hospital mortality [hazard ratio (HR) = 1.12, 95% confidence interval (95%CI) was 1.08-1.16, P = 0.006; HR = 1.04, 95%CI was 1.01-1.08, P = 0.030; HR = 1.08, 95%CI was 1.03-1.13, P = 0.023]. Higher average daily intake of protein and energy as well as lower mNUTRIC, SOFA, and APACHE II scores were also significantly correlated to lower 30-day mortality (HR = 0.45, 95%CI was 0.25-0.65, P < 0.001; HR = 0.77, 95%CI was 0.61-0.93, P < 0.001; HR = 1.10, 95%CI was 1.07-1.13, P < 0.001; HR = 1.07, 95%CI was 1.02-1.13, P = 0.041; HR = 1.15, 95%CI was 1.05-1.23, P = 0.014); however, there was no significant correlation between gender as well as number of complications and in-hospital mortality. Within 30 days of attack of sepsis, the average daily intake of protein and energy were not correlated to days of non-ventilator (HR = 0.66, 95%CI was 0.59-0.74, P = 0.066; HR = 0.78, 95%CI was 0.63-0.93, P = 0.073). Increase of patients' average daily intake of protein and energy were significantly correlated to a lower in-hospital mortality (HR = 0.41, 95%CI was 0.32-0.50, P < 0.001; HR = 0.87, 95%CI was 0.84-0.92, P < 0.001), shorter ICU stay (HR = 0.46, 95%CI was 0.39-0.53, P < 0.001; HR = 0.82, 95%CI was 0.78-0.86, P < 0.001), and hospital stay (HR = 0.51, 95%CI was 0.44-0.58, P < 0.001; HR = 0.77, 95%CI was 0.68-0.88, P < 0.001). According to correlation analysis, among patients with mNUTRIC score ≥ 5, increasing daily intake of protein and energy can reduce in-hospital mortality (HR = 0.44, 95%CI was 0.32-0.58, P < 0.001; HR = 0.73, 95%CI was 0.69-0.77, P < 0.001), and 30-day mortality (HR = 0.51, 95%CI was 0.37-0.65, P < 0.001; HR = 0.90, 95%CI was 0.85-0.96, P < 0.001); the receiver operator characteristic curve (ROC curve) further confirmed that higher protein intake had good predictive value for inpatient mortality area under the curve (AUC) = 0.96 and 30-day mortality (AUC = 0.94); higher emergy intake had good predictive value for inpatient mortality (AUC = 0.87) and 30-day mortality (AUC = 0.83). By contrast, among patients with mNUTRIC score < 5, it is only discovered that increasing daily intake of protein and energy can reduce 30-day mortality of patients (HR = 0.76, 95%CI was 0.69-0.83, P < 0.001). CONCLUSIONS: The increase of average daily intake of protein and energy for patients with sepsis is significantly correlated to reduction of in-hospital mortality and 30-day mortality, shorter ICU stay, and hospital stay. The correlation is more significant in patients with high mNUTRIC score, and higher intake of protein and energy can bring down in-hospital mortality and 30-day mortality. As for patients with low mNUTRIC score, nutritional support cannot improve prognosis of the patients significantly.

[Incidence of maternal sepsis in ICUs of hospitals in Beijing: a multicenter cohort study].

OBJECTIVE: To investigate the epidemiological data of maternal sepsis in intensive care unit (ICU), analyze the common causes, outcomes of maternal sepsis, and the risk factors of multi-drug resistant (MDR) bacteria. METHODS: A retrospective cohort study. Maternal sepsis cases admitted to ICUs of Peking University Third Hospital, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2008 to September 2022 were enrolled. The following data were recorded: demographic characteristics, sequential organ failure assessment (SOFA) during infection, infection time, infection sites, invasive intervention measures before infection, microbial culture results, blood routine test during infection, body temperature, and clinical outcomes caused by infection. According to the time of sepsis occurrence, the patients were divided into pre-ICU sepsis group and ICU sepsis group, and the causes of sepsis in the two groups were analyzed. According to whether MDR occurred, the patients were divided into MDR group and non-MDR group, and clinical outcomes were analyzed. Multivariate Logistic regression was used to analyze the risk factors of MDR bacteria infection in obstetrics with sepsis. RESULTS: 160 patients were enrolled, among which 104 cases of sepsis happened before ICU and 56 cases of sepsis happened during ICU, 53 cases were with MDR bacteria and 107 cases were without MDR bacteria. The median age of the patients was 30.5 (28.0, 34.0) years old, the median temperature was 38.8 (38.2, 39.5) centigrade, and the median white blood cell count (WBC) was 17.2 (13.2, 21.3)×109/L, the median SOFA score was 5.0 (3.0, 8.0), and 130 cases (81.2%) were referred from other hospitals. The main infection sites were uterine cavity in 64 cases (40.0%), lung in 48 cases (30.0%), abdominal and pelvic cavity in 30 cases (18.8%), urinary system in 27 cases (16.9%). Sepsis led to hysterectomy in 6 cases (3.8%), stillbirth in 8 cases (5.0%), and neonatal death in 2 cases (1.3%). The main surgical intervention measures were cesarean section (44 cases, accounting for 27.5%), followed by exploratory laparotomy (19 cases, 11.9%). The median length of ICU stay was 5.0 (3.0, 10.0) days, and the median hospital length was 14.0 (10.0, 20.8) days. Intrauterine infection was the primary cause of sepsis happened during ICU, accounting for 50.0% (28/56), of which postpartum hemorrhage accounted for 85.7% (24/28). The proportion of diabetes [28.3% (15/53) vs. 14.0% (15/107)], intrauterine operation [41.5% (22/53) vs. 23.4% (25/107)], intrauterine infection [50.9% (27/53) vs. 34.6% (37/107)] and bacteremia [18.9% (10/53) vs. 2.8% (3/107)] in the MDR group were significantly higher than those in the non-MDR group (all P < 0.05). Multivariate Logistic regression analysis showed that diabetes [odds ratio (OR) = 2.348, 95% confidence interval (95%CI) was 1.006-5.480, P = 0.048] and intrauterine operation (OR = 2.541, 95%CI was 1.137-5.678, P = 0.023) were independent risk factors for MDR bacterial infection in obstetrics with sepsis. CONCLUSIONS: Intrauterine infection is the common cause of maternal sepsis in ICU, and postpartum hemorrhage is the common cause of secondary intrauterine infection in ICU. MDR bacteria can lead to serious clinical outcomes. Diabetes and intrauterine operation are independent risk factors for MDR bacteria' infection.

[Analysis of risk factors of hyperpyrexia suffered by post neurosurgical patients after removal of drainage tube].

OBJECTIVE: To analyze the risk factors of hyperthermia after removal of drainage tubes in patients after neurosurgery. METHODS: The clinical data of 146 patients after neurosurgery with indwelling drainage tubes admitted to the department of critical care medicine of Pecking University Third Hospital from January 2019 to July 2021 were analyzed retrospectively. The patients were divided into hyperthermia group (body temperature ≥ 39 centigrade) and non-hyperthermia group (body temperature < 39 centigrade) according to whether their body temperatures within 24 hours after removal of drainage tubes. General clinical data and outcomes of the two groups were collected, and different tendentious scores were matched with the hyperthermia group and non-hyperthermia group based on Glasgow coma score (GCS), respectively. After such matching, the clinical baseline characteristics [age, gender, admission diagnosis, major complications, acute physiology and chronic health evaluation II (APACHE II) at admission, GCS], number of days of drainage tubes retention, location of drainage tubes, microbial culture results before removal of drainage tubes, white blood cell (WBC) and neutrophil ratio (NEU%) before and after removal of drainage tubes as well as clinical outcomes of the cohort patients were analyzed. The primarily outcome was in-hospital mortality, and then the length of intensive care unit (ICU) stay. RESULTS: A total of 146 patients after neurosurgery were included, 28 of which developed hyperthermia after removal of drainage tubes. The GCS scores at admission in the hyperthermia group were significantly lower than that in the non-hyperthermia group, while the proportion of hypertension and diabetes in the hyperthermia group was significantly higher than that in the non-hyperthermia group. Based on GCS scores, the two groups, each of which included 28 patients, were matched with tendentious scores, and there was no significant difference in gender, age, GCS scores and the proportion of hypertension and diabetes between the two groups. The main disease for patients upon admission was cerebral hemorrhage (53.6%, 30/56). The proportion of indwelling ventricular drainage tube retention in the hyperthermia group was significantly higher than that in the non-hyperthermia group [32.1% (9/28) vs. 7.1% (2/28), P < 0.05], but there was no significant difference in the location of other drainage tubes between the two groups. The proportion of lumbar puncture in the hyperthermia group was also significantly higher than that in the non-hyperthermia group [25.0% (7/28) vs. 0 (0/28), P < 0.05]. Compared with the non-hyperthermia group, WBC [×109/L: 13.0 (9.5, 15.2) vs. 11.5 (8.8, 13.3)] of 1 day before removal of drainage tubes, NEU% [0.892 (0.826, 0.922) vs. 0.843 (0.809, 0.909)] after removal of drainage tubes and positive rate of drainage-fluid culture or drainage-tube-tip culture [7.1% (2/28) vs. 0% (0/28)] in the hyperthermia group increased, but there were not significant differences. There was no significant difference in the proportion of pulmonary, urinary system and blood flow infection before removal of drainage tubes in the two groups. In terms of primary outcomes, compared with the non-hyperthermia group, the length of ICU stay [days: 17.0 (8.0, 32.3) vs. 8.5 (1.0, 16.8), P < 0.05] in the hyperthermia group was significantly prolonged, and the in-hospital mortality [35.7% (10/28) vs. 10.7% (3/28), P < 0.05] in the hyperthermia group was obviously increased. The positive rate of carbapenem-resistant bacteria culture [32.1% (9/28) vs. 3.6% (1/28), P < 0.05] in the hyperthermia group during hospitalization was significantly higher than that in the non-hyperthermia group. CONCLUSIONS: Hyperthermia after removal of drainage tubes for patients after neurosurgery can significantly prolong the length of ICU stay and increase the in-hospital mortality, which may be related to the secondary infection caused by indwelling intracranial drainage tubes and the intracranial spread of bacteria caused by removal of drainage tubes, as well as the intracranial multidrug-resistant bacterial infection caused by the drainage tubes.

Features of gut microbiota in patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a psychological disorder, which is characterized by the misunderstanding of body image, food restriction, and low body weight. An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota. The purpose of our study was to explore the features of gut microbiota in patients with AN, hoping to provide valuable information on its pathogenesis and treatment. METHODS: In this cross-sectional study, from August 2020 to June 2021, patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital ( n   =  30) were recruited as the AN group, and healthy controls (HC) were recruited from a middle school and a university in Beijing ( n   =  30). Demographic data, Hamilton Depression Scale (HAMD) scores of the two groups, and length of stay of the AN group were recorded. Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The weight (AN vs. HC, [39.31 ±â€Š7.90] kg vs. [56.47 ±â€Š8.88] kg, P  < 0.001) and body mass index (BMI, AN vs. HC, [14.92 ±â€Š2.54] kg/m 2vs. [20.89 ±â€Š2.14] kg/m 2 , P  < 0.001) of patients with AN were statistically significantly lower than those of HC, and HAMD scores in AN group were statistically significantly higher than those of HC. For alpha diversity, there were no statistically significant differences between the two groups; for beta diversity, the two groups differed obviously regarding community composition. Compared to HC, the proportion of Lachnospiraceae in patients with AN was statistically significantly higher (AN vs. HC, 40.50% vs. 31.21%, Z  = -1.981, P  = 0.048), while that of Ruminococcaceae was lower (AN vs. HC, 12.17% vs. 19.15%, Z  = -2.728, P  = 0.007); the proportion of Faecalibacterium (AN vs. HC, 3.97% vs. 9.40%, Z  = -3.638, P  < 0.001) and Subdoligranulum (AN vs. HC, 4.60% vs. 7.02%, Z  = -2.369, P  = 0.018) were statistically significantly lower, while that of Eubacterium_hallii_group was significantly higher (AN vs. HC, 7.63% vs. 3.43%, Z  = -2.115, P  = 0.035). Linear discriminant effect (LEfSe) analysis (LDA score >3.5) showed that o_Lachnospirales, f_Lachnospiraceae, and g_Eubacterium_hallii_group (o, f and g represents order, family and genus respectively) were enriched in patients with AN. Microbial function of nutrient transport and metabolism in AN group were more abundant ( P  > 0.05). In AN group, weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides , while positively correlated with Subdoligranulum . BMI was significantly positively correlated with Firmicutes; HAMD scores were significantly negatively correlated with Faecalibacterium. CONCLUSIONS: The composition of gut microbiota in patients with AN was different from that of healthy people. Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.

[Clinical characteristics of critically ill pregnant women with different admission methods to intensive care unit: data analysis from 2006 to 2019 in the university hospital].

OBJECTIVE: To compare the clinical characteristics of critically ill pregnant women admitted to the intensive care unit (ICU) with different admission methods, in order to make more effective and rational use of ICU resources. METHODS: A retrospective study was conducted. The clinical data of critically ill pregnant women admitted to ICU of Peking University Third Hospital from January 2006 to July 2019 were analyzed. According to the admission mode to ICU, the pregnant women were divided into emergency admission group (transferred to ICU on the same day or the next day due to critical illness) and planned admission group (transferred to ICU 2 days after admitting in obstetric ward). The clinical characteristics of ICU critical pregnant women, such as the incidence, causes of admission, severity of the disease, main treatment measures, mortality, and medical expenses were collected, and a comparative analysis between the two groups was performed. RESULTS: During the nearly 14 years, a total of 576 critical pregnant women in ICU were enrolled, accounting for 0.8% (576/71 790) of the total number of obstetric inpatients and 4.6% (576/12 412) of the total number of ICU inpatients. Seven maternal deaths accounted for 1.2% of all critically pregnant women transferred to ICU, and the overall mortality of pregnant women was 10/100 thousand. Of the 576 critically pregnant women, there were 327 patients (56.8%) in the emergency admission group and 249 patients (43.2%) in the planned admission group. Compared with the planned admission group, the proportion of elective cesarean section in the emergency admission group was significantly lower (17.7% vs. 94.0%, P < 0.01), and the proportion of emergency cesarean section was significantly higher (65.1% vs. 2.4%, P < 0.01), the acute physiology and chronic health evaluation (APACHE II, APACHE III) scores, simplified acute physiology score II (SAPS II) and Marshall score were significantly higher [APACHE II score: 6.0 (4.0, 9.8) vs. 4.0 (3.0, 7.0), APACHE III score: 14.0 (11.0, 20.3) vs. 12.0 (9.0, 16.0), SAPS II score: 8 (0, 12) vs. 3 (0, 8), Marshall score: 2 (1, 4) vs. 1 (1, 3), all P < 0.01]. The length of ICU stay in the emergency admission group was significantly longer than that in the planned admission group [days: 2 (1, 5) vs. 2 (1, 3), P < 0.01], and the total length of hospital stay was significantly shorter [days: 9 (7, 13) vs. 13 (10, 18), P < 0.01]. Both in the emergency admission group and the planned admission group, obstetric factors were the main reason for admission, 60.9% (199/327) and 70.3% (175/249), respectively. The proportion of postpartum hemorrhage was the highest [35.2% (115/327) and 57.0% (142/249)], followed by preeclampsia/eclampsia [7.0% (23/327) and 7.6% (19/249)]. Only 7 of the 19 critically pregnant women with puerperal infection were planned admission. All 21 patients with acute fatty liver of pregnancy (AFLP) during pregnancy were emergency admission. Among the emergency and planned admission patients, 73 patients (22.3%) and 42 patients (16.9%) required mechanical ventilation (duration of mechanical ventilation > 24 hours), 99 patients (30.3%) and 35 patients (14.1%) needed vasoactive agents, 67 patients (20.5%) and 20 patients (8.0%) received hemodynamic monitoring, and 123 patients (37.6%) and 154 patients (61.8%) were given anticoagulation therapy, respectively. In terms of severity score of critical pregnant women, there were significant differences in APACHE II, APACHE III, SAPS II and Marshall scores of pregnant women with different diseases. Among them, the APACHE III, SAPS II and Marshall scores of AFLP were the highest [21.0 (15.0, 32.5), 12.0 (6.0, 16.5) and 6.0 (3.5, 8.0), respectively]. The APACHE II and APACHE III scores of postpartum hemorrhage were the lowest [4.0 (3.0, 7.0), 12.0 (10.0, 16.0)]. The SAPS II score of pneumonia was the lowest [2.0 (0, 14.0)]. The Marshall score for puerperal infection was the lowest [1.0 (0, 3.0)]. In terms of the total medical expenses, the cost in the emergency admission group was significantly lower than that in the planned admission group [10 thousand Yuan: 3.1 (2.0, 4.7) vs. 4.1 (2.9, 5.8), P < 0.05]. CONCLUSIONS: Compared with the critically ill pregnant women who planned to be admitted to ICU, the patients emergency admitted to ICU were more complicated and urgent, and the severity of the condition was scored higher. At present, the severity scoring system commonly used in ICU can only partly evaluate the severity of critically ill pregnant women, therefore, it is necessary to design the specific severity scoring system for critically ill pregnant women to effectively and rationally use the precious ICU resources.

Disseminated intravascular coagulation associated organ failure in obstetric patients admitted to intensive care units: a multicenter study in China.

We aimed to determine disseminated intravascular coagulation (DIC)-associated organ failure and underlying diseases based on data from three ICU wards in tertiary hospitals in China from 2008 to 2016. The diagnosis of DIC was confirmed by an International Society of Thrombosis and Hemostasis score greater than or equal to 5. The maternal outcomes included the changes in organ function 24 h after ICU admission. The durations of hospital stay and ICU stay were recorded as secondary outcomes. Among 297 ICU admissions (median Sequential Organ Failure Assessment score, 4) for obstetric diseases, there were 87 DIC cases, with an estimated DIC incidence of 87 per 87,580 deliveries. Postpartum hemorrhage was the leading disease associated with DIC (71, 81.6%), followed by hypertensive disorders (27, 31.0%), sepsis (15, 17.2%), acute fatty liver of pregnancy (11, 12.6%) and amniotic fluid embolism (10, 11.5%). Compared with patients without DIC, those with DIC had higher rates of multiple organ dysfunction syndrome/death (27.6% vs 4.8%, p = 0.000), organ failure (36.8% vs 24.3%, p = 0.029), among which organ failure included acute renal failure (32.2% vs 10.0%, p = 0.000), respiratory failure (16.1% vs 8.6%, p = 0.057), disturbance of consciousness (12.6% vs 2.4%, p = 0.000) and DIC group also had higher rates of massive transfusion (52.9% vs 21.9%, p = 0.000), hysterectomy (32.2% vs 15.7%, p = 0.001), longer ICU (4 days vs 2 days, p = 0.000) and hospital stays (14 days vs 11 days, p = 0.005). DIC and amniotic fluid embolism were independent risk factors for organ failure in patients admitted to the ICU. Postpartum hemorrhage was the leading cause of DIC associated organ failure in obstetrics admitted to the ICU. The control of obstetric bleeding in a timely manner may improve obstetric prognoses.

[Effect of noninvasive positive pressure ventilation and high-flow nasal cannula oxygen therapy on the clinical efficacy of coronavirus disease 2019 patients with acute respiratory distress syndrome].

OBJECTIVE: To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS). METHODS: A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO2/FiO2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO2/FiO2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO2, SpO2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. RESULTS: Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ßvalues were -15.827, 1.202, 95% confidence interval (95%CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. CONCLUSIONS: Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

[Strengthening and improving the integration of traditional Chinese and Western medicine in severe tetanus therapy: retrospective study and analysis of survive and decease cases].

OBJECTIVE: To investigate the perfection and improvement of the execution of integrative medicine therapy in severe tetanus therapy, to successfully control tetanus severe spasms, autonomic dysfunction and prevent lethal side-effect of prolong and high-dosage sedative-muscle-relaxant therapy, resulted in significant reduction of mortality of tetanus. METHODS: Symptoms, treatments and outcome of tetanus patients admitted to Peking University Third Hospital from 1965 to 2020 were reviewed. Patients were classified with Ablett classification. The cases of Ablett grade III and IV were severe tetanus. The patients were divided into two groups according to whether they were treated together with traditional Chinese medicine (TCM) simultaneously during the standard tetanus treatment; the patients in the TCM group were divided into the tetanus TCM medication group and the non tetanus TCM medication group according to the medicine provided whether was in accord with the conventional tetanus TCM prescriptions. The mortality of each group was calculated. In addition, one survived and one deceased case with severe convulsion, autonomic nerve dysfunction (Ablett grade IV) were selected, combined with the treatment methods and curative effects, the types, use methods and outcomes of Chinese and Western medicine were analyzed. RESULTS: The 46 tetanus cases were treated with Western medicine. Twenty-two of them, TCM were applied. Fifteen of the 22 cases took the TCM prescription which was accord with the conventional tetanus prescription. The mortality of the 46 cases was 21.7% (10/46). The number of non-TCM group was 24 cases, with mortality of 20.8% (5/24); 1 case was Ablett II, 1 was Ablett III and 3 were Ablett IV. The number of the TCM group was 22 cases, with mortality of 22.7% (5/22), 2 cases were Ablett III, 3 were Ablett IV. The TCM prescription of these 5 deceased cases was not directed towards tetanus. The tetanus TCM medication group was 15 cases, with no mortality. Case analyses: case 1 was intubated because of severe spasms. Autonomic dysfunction occurred on the 8th day after admission. Esmolol with increasing the dosage of the sedatives and muscle relaxant, was not effective. Tetanus TCM was applied after 2 days of autonomic dysfunction happened. Autonomic dysfunction was then under controlled on the 2nd day post-TCM. She was recovery and discharged after 4 weeks. Case 2, also was intubated because of severe spasms. Autonomic dysfunction happened on the 3rd day after admission, and failed to be controlled by large-dose sedatives, muscle relaxant,and Esmolol. After 8 days of persistent autonomic dysfunction, tetanus TCM was applied and autonomic dysfunction was under controlled on the 2nd day post-TCM administration. Large dosage of muscle-relaxant was applied continuously. After 5 days' administration of TCM, the TCM was withdrew. One day after the withdrawal of TCM, respiratory and cardiac arrest happened because of the diffused bronchiole obstruction with pulmonary secretions loading. CONCLUSIONS: Based on the precise and real-time diagnosis of the state of the disease, integrative medicine therapy with an overall analysis tetanus TCM prescription, is the key of declining tetanus mortality.

Prevention of Severe Intestinal Barrier Dysfunction Through a Single-Species Probiotics is Associated With the Activation of Microbiome-Mediated Glutamate-Glutamine Biosynthesis.

INTRODUCTION: Intra-abdominal hypertension (IAH), the leading complication in the intensive care unit, significantly disturbs the gut microbial composition by decreasing the relative abundance of Lactobacillus and increasing the relative abundance of opportunistic infectious bacteria. METHODS: To evaluate the preventative effect of Lactobacillus-based probiotics on IAH-induced intestinal barrier damages, a single-species probiotics (L92) and a multispecies probiotics (VSL#3) were introduced orally to Sprague-Dawley rats for 7 days before inducing IAH. The intestinal histology and permeability to macromolecules (fluoresceine isothiocyanate, FITC-dextran, N = 8 for each group), the parameters of immunomodulatory and oxidative responses [monocyte chemotactic protein 1 (MCP-1), interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interleukin-10 (IL-10), malonaldehyde, glutathione peroxidase (GSH- Px), catalase (CAT), and superoxide dismutase; N = 4 for each group], and the microbiome profiling (N = 4 for each group) were analyzed. RESULTS: Seven-day pretreatments of L92 significantly alleviated the IAH-induced increase in intestinal permeability to FITC-dextran and histological damage (P  < 0.0001), accompanied with the suppression of inflammatory and oxidative activation. The increase of MCP-1 and IL-1ß was significantly inhibited (P  < 0.05); the anti-inflammatory cytokines, IL-4, and IL-10 were maintained at high levels; and the suppression of CAT (P  <  0.05) was significantly reversed when pretreated with L92. On the contrary, no significant protective effects were observed in the VSL#3-pretreated group. Among the 84 identified species, 260 MetaCyc pathways, and 217 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the protective effects of L92 were correlated with an increased relative abundance of Bacteroides finegoldii, Odoribacter splanchnicus, and the global activation of amino acid biosynthesis pathways, especially the glutamate-glutamine biosynthesis pathway. CONCLUSIONS: Seven-day pretreatment with a single-species probiotics can prevent IAH-induced severe intestinal barrier dysfunction, potentially through microbial modulation.

Predictors of 1-year mortality in patients on prolonged mechanical ventilation after surgery in intensive care unit: a multicenter, retrospective cohort study.

OBJECTIVES: The requirement of prolonged mechanical ventilation (PMV) is associated with increased medical care demand and expenses, high early and long-term mortality, and worse life quality. However, no study has assessed the prognostic factors associated with 1-year mortality among PMV patients, not less than 21 days after surgery. This study analyzed the predictors of 1-year mortality in patients requiring PMV in intensive care units (ICUs) after surgery. METHODS: In this multicenter, respective cohort study, 124 patients who required PMV after surgery in the ICUs of five tertiary hospitals in Beijing between January 2007 and June 2016 were enrolled. The primary outcome was the duration of survival within 1 year. Predictors of 1-year mortality were identified with a multivariable Cox proportional hazard model. The predictive effect of the ProVent score was also validated. RESULTS: Of the 124 patients enrolled, the cumulative 1-year mortality was 74.2% (92/124). From the multivariable Cox proportional hazard analysis, cancer diagnosis (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.37-3.35; P < 0.01), no tracheostomy (HR 2.01, 95% CI 1.22-3.30; P < 0.01), enteral nutrition intolerance (HR 1.88, 95% CI 1.19-2.97; P = 0.01), blood platelet count ≤150 × 109/L (HR 1.77, 95% CI 1.14-2.75; P = 0.01), requirement of vasopressors (HR 1.78, 95% CI 1.13-2.80; P = 0.02), and renal replacement therapy (HR 1.71, 95% CI 1.01-2.91; P = 0.047) on the 21st day of mechanical ventilation (MV) were associated with shortened 1-year survival. CONCLUSIONS: For patients who required PMV after surgery, cancer diagnosis, no tracheostomy, enteral nutrition intolerance, blood platelet count ≤150 × 109/L, vasopressor requirement, and renal replacement therapy on the 21st day of MV were associated with shortened 1-year survival. The prognosis in PMV patients in ICUs can facilitate the decision-making process of physicians and patients' family members on treatment schedule.

Enteral nutrition feeding in Chinese intensive care units: a cross-sectional study involving 116 hospitals.

BACKGROUND: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. METHODS: This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. RESULTS: A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2-19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2-3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353-0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008-0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient - 0.002, 95% CI - 0.008 to - 0.001; p = 0.024) and male gender (coefficient - 0.144, 95% CI - 0.203 to - 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2-3 was associated with lower EN proportion (coefficient - 0.206, 95% CI - 0.273 to - 0.139; p < 0.001). CONCLUSIONS: The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.

Pregnancy-Related ICU Admissions From 2008 to 2016 in China: A First Multicenter Report.

OBJECTIVES: To identify the key points for improving severe maternal morbidity by analyzing pregnancy-related ICU admissions in Beijing. DESIGN: This was a retrospective, multicenter cohort study. SETTING: Three ICUs in tertiary hospitals in Beijing. PATIENTS: A total of 491 severe maternal cases in any trimester of pregnancy or within 42 days of delivery were reviewed between January 1, 2008, and December 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 491 obstetric ICU admissions (median Sequential Organ Failure Assessment score, 2) out of 87,850 hospital deliveries (a frequency of 5.6 admissions per 1,000 deliveries), the leading diagnoses were postpartum hemorrhage (170; 34.62%), hypertensive disorders of pregnancy (156; 31.77%), and cardio-cerebrovascular diseases (78; 15.9%). Comparing 2008-2011 to 2012-2016, the rates of maternal mortality (2.5% vs 1.9%; p = 0.991) and fetal loss (8.5% vs 8.6%; p = 0.977) did not decrease significantly, whereas the rates of ICU admission (3.05% vs 7.85%; p trends < 0.001) and postpartum hemorrhage (23% vs 38.5%; p = 0.002) increased. Hypertensive disorder (150/156; 96.2% transferred to the ICU postpartum, 24/28 women with fetal loss transferred from lower-level hospitals) was an independent maternal factor associated with fetal loss, and infections were the leading cause of maternal death (6/10) in the ICU. CONCLUSIONS: Our study highlights the increasing rate of intensive care admissions for postpartum hemorrhage. Improving prenatal care quality for pregnancy-induced hypertension and sepsis at lower-level hospitals may improve maternal and fetal outcomes. Specifically, providing more effective regional cooperation before transfer and shifting patients who require continuous surveillance but not necessarily intensive care to a transitional ward in a tertiary hospital would provide more ICU beds for more prenatal intensive care for the most complex medical conditions.

[Assessing nutritional status of severe malnutrition patients by bioelectrical impedance technique: a multicenter prospective study].

OBJECTIVE: To assess the nutritional status of severe malnutrition patients with anorexia nervosa by multi-frequency bioelectrical impedance technique, and to provide the basis for nutritional support therapy. METHODS: A prospective study was conducted. Twenty-six severe malnutrition patients with anorexia nervosa, body mass index (BMI) ≤ 16 kg/m2 admitted to intensive care unit (ICU) of Peking University Third Hospital and general three ward of Peking University Sixth Hospital from June 1st to September 30th, 2017 were enrolled. The extracellular water (ECW), intracellular water (ICW), ECW/ICW ratio, adipose tissue mass (ATM), lean tissue mass (LTM), total body water/body weight (TBW/WT), ATM/WT, and LTM/WT were measured by multi-frequency bioelectrical impedance meter. Thirty-eighty healthy volunteers with normal nutritional status (23.0 kg/m2 > BMI > 18.5 kg/m2) matched by gender and height were enrolled as healthy control group. The predictive value of main body composition for nutritional status were analyzed by receiver operating characteristic (ROC) curve. RESULTS: All the patients were female. There was no significant difference in height between two groups, but WT and BMI in the severe malnutrition group were significantly higher than those in the healthy control group [WT (kg): 38.1±4.9 vs. 54.2±3.3, BMI (kg/m2): 13.6±2.5 vs. 21.2±1.1, both P < 0.01]. Compared with the healthy control group, the ECW, ICW, ATM, LTM, ATM/WT and LTM/WT were significantly decreased in the severe malnutrition group [ECW (L): 9.02±0.42 vs. 10.19±0.77, ICW (L): 12.6±0.9 vs.19.1±1.3, ATM (kg): 9.3±1.1 vs. 16.6±1.9, LTM (kg): 16.5±1.5 vs. 26.1±1.7, ATM/WT: 0.26±0.02 vs. 0.30±0.02, LTM/WT: 0.22±0.02 vs. 0.26±0.01, all P < 0.01], the ECW/ICW and TBW/WT were significantly increased in the severe malnutrition group (ECW/ICW: 0.72±0.06 vs. 0.54±0.06, TBW/WT: 0.58±0.02 vs. 0.52±0.02, both P < 0.01). It was shown by ROC curve analysis that the area under ROC curve (AUC) of TBW/WT, ATM/WT, LTM/WT for evaluating severe malnutrition were 0.999, 0.919, 0.954 respectively; when the cut-off of TBW/WT, ATM/WT, LTM/WT were 0.58, 0.28, 0.24 respectively, the sensitivity were 100%, 85%, 80% respectively, and the specificity were 95%, 80%, 91% respectively. CONCLUSIONS: Main body composition of severe malnutrition patients with anorexia nervosa changed significantly. Bioelectrical impedance technology can be an effective assessment tool for the nutritional status of such patients.

[Effects of antibiotics on intestinal microflora and intestinal mucosal barrier function and its mechanisms].

Antibiotics are the cornerstone to cure infectious diseases, however, it also destroys the intestinal inherent microflora, and may cause serious gastrointestinal dysfunction, such as abdominal distension, diarrhea, mucosal barrier damage etc. In severe conditions, it may induce intestinal sepsis. With the development of the human microbiology group program and the popularity of microbial sequencing technology, people can comprehend the effects of antibiotics on intestinal flora deeply, meanwhile the traditional biomedical model (the basis of bacterial disease) is questioned. It presents the effects and mechanisms of antibiotics on intestinal microflora and intestinal mucosal barrier function in detail and demonstrates the feasibility by the treatment of probiotics and fecal transplantation to construct "health-promoting microbes" to adjust gastrointestinal function, in addition, it can promote the rational use of antibiotics.

MICU1 may be a promising intervention target for gut-derived sepsis induced by intra-abdominal hypertension.

Intra-abdominal hypertension (IAH) is a common and serious complication in critically ill patients, for which there is no targeted therapy. IAH-induced dysfunction of intestinal barriers is closely associated with oxidative imbalances, which are considered to provide a pathophysiological basis for subsequent gut-derived sepsis. However, the upstream mechanism that produces oxidative damage during IAH remains unknown. It is not clear whether 'mitochondrial Ca2+ uptake 1' (MICU1, the key protein regulating the oxidative process) is involved in preventing Ca2+m (mitochondrial Ca2+) overload. Here, we detected changes in the expression of MICU1 during the development of increased intestinal permeability in rats with IAH, and we explored the related mechanism regulating epithelial-barrier functions by knocking-down micu1 in Caco-2 cells. Our results demonstrated that, to combat IAH-induced dysfunction of intestinal barriers, MICU1 undergoes a compensatory increase in expression, whereas 'mitochondrial calcium uniporter' (MCU) - a conserved Ca2+ transporter - becomes transcriptionally suppressed. Silencing the expression of MICU1 destroyed Caco-2 cell barrier integrity, promoted paracellular permeability, and impaired the expression of tight junction proteins (occludin, ZO-1, and claudin 1). Meanwhile, oxidative imbalances were induced; malondialdehyde (MDA), a product of oxidation, was increased and antioxidant products (GSH-Px, CAT, and SOD) were decreased. In MICU1-deficient Caco-2 cells, proliferation was inhibited and apoptosis was promoted. Collectively, our results indicate that MICU1-related oxidation/antioxidation disequilibrium is strongly involved in IAH-induced damage to intestinal barriers. MICU1-targeted treatment may hold promise for preventing the progression of IAH to gut-derived sepsis.

Effect of traditional Chinese medicine on intra-abdominal hypertension and abdominal compartment syndrome: A systematic review and Meta-analysis.

OBJECTIVE: Traditional Chinese medicine (TCM) recently become a widely used treatment option for treating intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). However, we still lack large-scale, high-quality, randomized controlled trials (RCTs). The purpose of this systematic review was to evaluate the existing clinical trials and to provide additional specific evidence. METHODS: A systematic review of randomized controlled trials (RCTs) of TCM for IAH/ACS was conducted. The following databases were searched to identify relevant studies: PubMed, Medline (Ovid SP), The Cochrane Library, China Biology Medicine Database, Wanfang Database, Chinese Periodical Database, Chinese Clinical Trial Registry, and China Knowledge Resource Integrated Database. Meta-analysis was performed using Rev. Man 5.3. RESULTS: Fifteen studies involving 735 participants were included in the analysis. Compared to conventional therapy, TCM has a significant effect on reducing intra-abdominal pressure (IAP) [15 studies, 700 patients, standard mean difference (SMD)=-0.93, 95% credibility interval (CI): -1.35- -0.52], improving the APACHE II (five studies, 199 patients, SMD=-0.75, 95% CI: -1.30- -0.21), and shortening the length of hospitalization (LOH) (six studies, 214 patients, SMD=-1.21, 95% CI: -1.50- -0.91). The influence of mortality (six studies, 241 patients) was not significant [The pooled risk ratio (RR) was -0.07 (95% CI: -0.17- 0.03)]. CONCLUSIONS: TCMs seem to be effective for patients with IAH and ACS; however, most of the reviewed trials are of poor quality. Large-scale, high-quality clinical trials are warranted.

Effects of acute intra-abdominal hypertension on multiple intestinal barrier functions in rats.

Intra-abdominal hypertension (IAH) is a common and serious complication in critically ill patients for which there is no well-defined treatment strategy. Here, we explored the effect of IAH on multiple intestinal barriers and discussed whether the alteration in microflora provides clues to guide the rational therapeutic treatment of intestinal barriers during IAH. Using a rat model, we analysed the expression of tight junction proteins (TJs), mucins, chemotactic factors, and Toll-like receptor 4 (TLR4) by immunohistochemistry. We also analysed the microflora populations using 16S rRNA sequencing. We found that, in addition to enhanced permeability, acute IAH (20 mmHg for 90 min) resulted in significant disturbances to mucosal barriers. Dysbiosis of the intestinal microbiota was also induced, as represented by decreased Firmicutes (relative abundance), increased Proteobacteria and migration of Bacteroidetes from the colon to the jejunum. At the genus level, Lactobacillus species and Peptostreptococcaceae incertae sedis were decreased, whereas levels of lactococci remained unchanged. Our findings outline the characteristics of IAH-induced barrier changes, indicating that intestinal barriers might be treated to alleviate IAH, and the microflora may be an especially relevant target.

[Impacts of sepsis-induced myocardial dysfunction on hemodynamics, organ function and prognosis in patients with septic shock].

OBJECTIVE: To investigate the impacts of sepsis-induced cardiac dysfunction on hemodynamics, organ function and prognosis in the patients with septic shock. METHODS: A prospective cohort study was conducted in 44 patients suffering from septic shock with the duration < 24 hours admitted to the Department of Critical Care Medicine of Peking University Third Hospital during June 2013 to June 2014. The patients were divided into two groups according to the left ventricular ejection fraction (LVEF) as recorded in echocardiogram at time of admission to the intensive care unit (ICU) as sepsis-induced myocardial dysfunction group (LVEF < 0.50, n = 11) and normal cardiac function group (LVEF ≥ 0.50, n = 33). The cardiac function evaluation and hemodynamics monitoring were performed with echocardiogram and pulse-induced contour cardiac output (PiCCO) on 1, 3, 7 days after the ICU admission. The plasma levels of the biomarkers of myocardial damage, troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured, and the parameters representing organ function and the 28-day prognosis were collected as well. RESULTS: On the ICU admission, central venous pressure (CVP) and left ventricular end-diastolic diameter (LVEDD) were obviously lower in normal cardiac function group than those of myocardial dysfunction group [CVP (mmHg, 1 mmHg = 0.133 kPa): 10 ± 4 vs. 14 ± 6, P < 0.05; LVEDD (mm): 45.0 ± 5.3 vs. 51.8 ± 7.1, P < 0.01], and there was no significant difference in other hemodynamic parameters between two groups. On the 3rd day, all the cardiac function and hemodynamic parameters showed no significant differences between the two groups. On the 7th day, the cardiac index (CI) and pulmonary vascular permeability index (PVPI) of normal cardiac function group were significantly higher than those of myocardial dysfunction group [CI (mL×s⁻¹×m⁻²): 63.3 ± 13.3 vs. 48.3 ± 10.0, P <0.05; PVPI: 1.5 (1.4, 1.9) vs. 1.1 (0.7, 1.1), P < 0.01], and no significant difference was found in the other parameters. The plasma levels of TnT and NT-proBNP were found to have no difference at three time points between two groups. There was no difference in the number or the extent of organ dysfunction, including lung, kidney, liver and coagulation system, between the groups at the time of ICU admission. There was no obvious difference in the 28-day survival rate between the myocardial dysfunction group and normal cardiac function group [81.8% (9/11) vs. 72.7% (24/33), χ² = 0.398, P = 0.528]. CONCLUSIONS: Sepsis-induced myocardial dysfunction is a reversible organ dysfunction. It can directly induce decreased left ventricular systolic function and enlargement of ventricle in patients with septic shock without reducing cardiac output or impairing the functions of other organs, or elevating the mortality rate.

Papaverine improves sublingual blood flow in patients with septic shock.

BACKGROUND: In recent years, microcirculatory blood flow alterations have been recognized to be stronger predictors of septic shock treatment outcomes than global hemodynamic variables. METHODS: In our self-controlled, interventional pilot clinical trial study, we investigated the effects of a single papaverine injection on the microcirculation in sepsis patients undergoing fluid resuscitation combined with vasopressor treatments. Fourteen septic shock patients admitted to the Peking University Third Hospital were included in the study, and each patient received 30 mg papaverine, which is the approximate dosage used to treat a conventional arterial spasm. Papaverine was administered as an intravenous bolus injection after systemic hemodynamic stabilization had been achieved by means of fluid resuscitation combined with dopamine and/or norepinephrine vasopressor medication. Baseline characteristics, as well as global hemodynamic and blood gas parameters, before and 60 min after papaverine injection were recorded and sublingual microcirculatory data at baseline and 15, 30, and 60 min after papaverine administration obtained using sidestream dark-field video microscopy. RESULTS: The perfused vessel density of small vessels was significantly increased 30 and 60 min after papaverine administration (P < 0.01), and the proportion of perfused small vessels (PPV), as well as the microvascular flow index, was significantly increased 30 min after papaverine (P < 0.05). There were no visible systemic effects, arrhythmia, or hypotension during the observation period in each patient. CONCLUSIONS: In our pilot study, papaverine transiently improved sublingual microcirculatory blood flow without influencing systemic hemodynamics in patients with septic shock, who required vasoconstrictors to maintain blood pressure during fluid resuscitation.