A Pilot Study of the Use of Dexmedetomidine for the Control of Delirium by Reducing the Serum Concentrations of Brain-Derived Neurotrophic Factor, Neuron-Specific Enolase, and S100B in Polytrauma Patients.

BACKGROUND: Delirium is very common among patients with polytrauma, although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients. Recent reports have suggested that continuous intravenous (IV) infusions of dexmedetomidine, rather than benzodiazepine, be administered for sedation to reduce the duration of delirium in this population. However, serum neuron-specific enolase (NSE), S100 calcium binding protein B (S100B), and brain-derived neurotrophic factor (BDNF) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives. The aim of this study was to assess the association of blood BDNF, NSE, and S100B with the occurrence of delirium among polytrauma patients who had been sedated with dexmedetomidine. MATERIALS AND METHODS: Consecutive patients were randomly assigned to 1 of 2 treatment study groups, namely the "dexmedetomidine group" or the "common group." This case-control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit (ICU). Blood samples were collected from all patients upon ICU admission, on the day when delirium was diagnosed, and on days 3 and 5 following diagnosis. The serum levels of S100B, BDNF, and NSE were determined by enzyme-linked immunosorbent assay. The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU. RESULTS: The median BDNF, NSE, and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed. The rate of delirium was significantly lower in the dexmedetomidine group than in the common group. There were clear differences in the BDNF, NSE, and S100B levels between the 2 groups on the fifth day after delirium was diagnosed. CONCLUSIONS: Our randomized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF, S100B, and NSE levels, which appear to be associated with the occurrence of delirium in the dexmedetomidine group.

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Novel avian-origin influenza A (H7N9) in critically ill patients in China*.

OBJECTIVES: In March 2013, human infection with a novel avian-origin reassortment influenza A (H7N9) virus was identified in China. A total of 26 cases were confirmed and treated in Jiangsu. All the patients had findings consistent with pneumonia and were admitted to an ICU, which pose a threat to human health. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with H7N9 viral infection. DESIGN: A retrospective cohort study. SETTING: Eight closed ICUs in general hospitals distributed throughout the Jiangsu Provincial, China. PATIENTS: Patients infected with influenza A (H7N9) virus from March 20, 2013, through May 1, 2013, in Jiangsu Province were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients infected with H7N9 virus were identified in Jiangsu. Of these, 26 were hospitalized. The median age was 54.5 years, and 18 patients (69.2%) were men. The most common symptoms at the onset of illness were high fever and cough. White cell counts were normal or decreased. All the patients had findings consistent with pneumonia. Twenty-four patients (92.3%) developed acute respiratory distress syndrome, and 10 (38.5%) developed septic shock quickly after the onset of illness. Treatment with antiviral drugs was initiated in all the patients at a median of 8 days after the onset of illness. Mortality was 19.2% at 28 days and 30.8% at 90 days. Based on multiple logistic regression analysis, septic shock associated with severe hypoxemia was the only independent risk factor for mortality. CONCLUSIONS: Infection with novel avian-origin reassortment influenza A (H7N9) virus is characterized by high fever, cough, and severe respiratory failure and is associated with a high mortality. These data provide some general understandings for the early identification, ICU treatment, and short-term prognosis of hospitalized critical patients with H7N9.

The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome.

INTRODUCTION: Recent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS. METHODS: This prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment. RESULTS: Within 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO2/FiO2. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001). CONCLUSIONS: The Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.

[Analysis of early lactate clearance rate in prognosis of neural function of patients with cardiac arrest].

OBJECTIVE: To explore the correlations between early lactate clearance and the prognosis of neural function of patients with cardiac arrest (CA). METHODS: The total number of patients with CA and restored spontaneous circulation was 74. Their general clinical data such as gender, age, cause of CA, heart rhythm pre-CA, CA duration, resuscitation time, Apache II score, mean arterial pressure (MAP) and presence or absence of convulsion or central hyperthermia were recorded. The levels of lactate at admission and after 6 h's therapy were also collected and used for calculating the 6 h lactate clearance rate for each patient. According to the cerebral performance category, they were divided into two groups of better neural function (CPC1-2, A, n = 24) and worse neural function (CPC3-5, B, n = 50). General clinical data, lactate level and lactate clearance rate of two groups were compared to determine whether or not there was a significant difference. Logistic regression analysis was also used to select independent prognostic factors of neural function. RESULTS: No significant differences existed in gender, age, cause of CA, heart rhythm before CA, Apache II score, MAP, number of cases with concurrent convulsion or central hyperthermia (P > 0.05). And CA duration and save resuscitation time had significant inter-group differences (7.92 vs 11.16, 17.47 vs 23.80, P < 0.05). The lactate level at admission had no significant inter-group difference (10.7 vs 11.2, P > 0.05) while the 6 h's lactate level of group A was significantly less than that of group B (7.05 vs 5.26, P < 0.05). And the 6 h lactate clearance rate in group A was also significant higher than that in group B (48.79% vs 33.67%, P < 0.05). Logistic regression analysis revealed that 6 h lactate clearance rate and CA duratio were independent prognostic factors for neurological function in post-cardiac arrest patients. CONCLUSION: Early lactate clearance may be associated with the prognosis of neural function for CA patients.

[Severity analyese of acute pancreatitis based on etiology].

OBJECTIVE: To explore the relationship between etiology and severity of acute pancreatitis (AP). METHODS: A total of 486 AP patients, hospitalized at digestive, general surgery or critical care medicine departments from May 2012 to May 2014, were recruited retrospectively. And the data of clinical features, etiology and severity classification of AP according to the revised Atlanta criteria (2012) were collected. The relationships between different gender, age group, etiology and severity of disease were compared. RESULTS: The etiology distribution was as follows: gallstone (n = 296, 60.9%), hyperlipidemia (n = 93, 19.1%), alcohol (n = 48, 9.9%) and other causes (n = 49, 10.1%). And the severity was mild AP (MAP, n = 387, 79.6%), moderate-severe AP (MSAP, n = 53, 10.9%) and severe AP (SAP, n = 46, 9.5%). The proportion of females for gallstone AP was slightly higher than that of males (1.23: 1). However, for hyperlipidemic and alcoholic AP, the proportion of males was significantly higher than that of females (P = 0.00). The onset age of gallstone AP was generally over 40 years while hyperlipidemic and alcoholic AP tended to occur in patients aged under 60 years (P = 0.00). Among all age groups, the group of over 60 years had the highest MSAP incidence of 14% while <40-year-old group the highest incidence of SAP at 11.3%. And the >60-year-old group had the highest total incidence of MSAP and SAP at 22.2%. Compared with gallstone, alcohol and other causes, hyperlipidemic AP had a higher risk of MSAP and SAP (P = 0.028). CONCLUSION: Gallstone remains a leading cause of AP. Hyperlipidemic pancreatitis has shown a rising tendency in recent years and it often result in a more serious clinical process. And the clinicians should pay more attention to health education of patients.

[The effect of mild sedation on the prognosis and inflammatory markers in critical patients with mechanical ventilation].

OBJECTIVE: To compare the effect of slight and usual sedation on the prognosis and inflammatory marker levels in patients receiving mechanical ventilation in ICU. METHODS: We enrolled 78 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 48 h. The patients were prospectively and randomly assigned to receive: slight sedation (Richmond Agitation Sedation Score -1 to 0, n = 38 patients) or usual sedation (Richmond Agitation Sedation Score -3 to -2, n = 40 patients). Sedative dosages, duration of mechanical ventilation, length of ICU stay, complications (ventilator-associated pneumonia, tracheotomy) , adverse reactions (accidental extubation, reintubation, barotrauma) and levels of inflammatory markers on the day of sedation time for 48 h were recorded. RESULTS: When compared with the usual sedation group, duration of mechanical ventilation (d) ( 8 ± 5 vs 13 ± 8, P < 0.05) and length of ICU stay (d) ( 12 ± 10 vs 22 ± 9, P < 0.05) were significantly shorter in the slight sedation group. The total doses of midazolam (mg) , propofol (mg) and fentany (µg) were lower in the slight sedation group than those in the usual sedation group (275 ± 85 vs 575 ± 142, 4 562 ± 1 128 vs 7 434 ± 1 712 and 2 332 ± 1 458 vs 4 124 ± 2 743, P < 0.05) . Accidental extubation (5% vs 3%) , reintubation (5% vs 10%) and barotraumas (3% vs 8%) showed no differences between the 2 groups (P > 0.05). In the slight sedation group, the incidences of ventilator-associated pneumonia (26% vs 53%) and tracheotomy (18% vs 48%) were significantly decreased compared with those in the usual group. The levels of IL-1 (35 ± 12 vs 47 ± 18, P < 0.05) ng/L, IL-6 (49 ± 21 vs 62 ± 27, P < 0.05) ng/L, TNF-α ( 39 ± 16 vs 52 ± 25, P < 0.05) ng/L and CRP (95 ± 41 vs 125 ± 45, P < 0.05) mg/L were also lower in the slight sedation group than those in the conventional group. There were no differences in ICU mortality and 28 d-survival rate between the 2 groups. CONCLUSION: Slight sedation was shown to reduce the length of mechanical ventilation and ICU stay. It also decreased the levels of inflammatory markers while didn't increase the incidence of adverse reactions.

[The effects of real-time continuous glucose monitoring on oxidative stress and mortality in critically ill patients].

OBJECTIVE: To evaluate the effects of real-time continuous glucose monitoring (RT-CGM) system on oxidative stress and mortality in critically ill patients and to explore the correlation between glucose index, oxidative stress and mortality. METHODS: Selected 123 cases of critically ill patients were enrolled in this prospective randomized controlled study. They were randomly divided into the RT-CGM group (n = 61) and blood glucose meter group (GM group, n = 62). The following parameters were compared between the two groups: mean amplitude of glucose excursions (MAGE), hypoglycemia incidence, low blood glucose index (LBGI), high blood glucose index (HBGI), 28-day mortality and plasma level of 8-iso-PGF2α (8-iso) at 48 hours (R2), 72 hours (R3) and 96 hours (R4) after admission to ICU. The correlation between glucose index and plasma level of 8-iso-PGF2α were analyzed. The correlation between glucose index, plasma 8-iso level and 28-day death were analyzed. RESULTS: The parameters of MAGE, hypoglycemia incidence, LBGI and HBGI in the RT-CGM group and the GM group were (3.73 ± 1.09) mmol/L and (4.19 ± 1.11) mmol/L (P = 0.02), 3.28% and 14.52% (P = 0.03), 0.0011 and 0.0119 (P < 0.01) and 0.2258 and 0.3697 (P < 0.01), respectively. The plasma levels of 8-iso at R2, R3, R4 in the RT-CGM group and the GM group were (111.44 ± 16.99) ng/L and (114.03 ± 14.64) ng/L (P = 0.37), (94.53 ± 14.92) ng/L and (110.31 ± 13.42) ng/L (P < 0.01) and (57.84 ± 12.22) ng/L and (84.41 ± 14.16) ng/L (P < 0.01), respectively. The r values between MAGE, LBGI, HBGI and the plasma level of 8-iso were 0.69, 0.71 and 0.67, respectively (all P values < 0.01). Multivariate stepwise regression analysis showed MAGE, LBGI, HBGI entered final models (corrected R2 = 0.61, P < 0.01) with ß values of 0.64, 0.65 and 0.6 respectively (all P values < 0.01). The 28-day mortality in the RT-CGM group and the GM group was 9.84% and 30.65% (P < 0.01). The OR values of MAGE, hypoglycemia incidence, LBGI, HBGI and the plasma level of 8-iso for 28-day death were 2.14 (0.98 - 4.35), 3.43 (1.12 - 5.82), 2.67 (1.01 - 5.14), 1.32 (0.24 - 2.96) and 1.89 (0.67 - 3.44), respectively. CONCLUSION: RT-CGM can optimize the care in critically ill patients by improving hypoglycemia, hyperglycemia, glucose variability and oxidative stress and bring more detailed concern in the process, and to reduce the mortality.

[Causes and prognosis analysis of hyperdynamic left ventricular ejection fraction in intensive care unit patients with sepsis].

OBJECTIVE: To analyze the causes of hyperdynamic left ventricular ejection fraction (LVEF) in sepsis patients in the intensive care unit (ICU) and its impact on prognosis. METHODS: A retrospective cohort study was conducted. The clinical data of 273 sepsis patients admitted to the department of critical care medicine of the Affiliated People's Hospital of Jiangsu University from January 2018 to October 2021 were collected including gender, age, severity score, comorbidities, source of infection, vital signs, transthoracic echocardiographic (TTE) parameters, fluid intake and output, vasoactive drug dose, therapeutic measures and prognostic indicators. The patients were divided into normal LVEF group (LVEF 0.55-0.70), low LVEF group (LVEF < 0.55) and hyperdynamic LVEF group (LVEF > 0.70) according to the TTE examination results within 7 days of ICU admission. The clinical indicators among the three groups were compared and analyzed, and multivariate Logistic regression analysis was used to screen risk factors for the development of hyperdynamic LVEF in patients with sepsis. Spearman correlation analysis was used to determine the correlation between the mortality of different types of LVEF and clinical variables. RESULTS: Among 273 patients, 20 patients with severe valvular or cardiomyopathy at admission and those who did not completed cardiac ultrasound within 7 days of ICU admission were excluded. A total of 253 patients were finally enrolled, including 169 patients in the normal LVEF group, 40 patients in the low LVEF group, and 44 patients in the hyperdynamic LVEF group. There were statistically significant differences in age, sequential organ failure assessment (SOFA) score, central venous pressure (CVP), heart rate (HR), oxygenation index (PaO2/FiO2), blood lactate (Lac), urine output, vasoactive drug dose, ratio of hypertension, ischemic heart disease, chronic liver disease, cancer, invasive mechanical ventilation and renal replacement therapy (RRT), and incidence of septic shock among the different types of LVEF groups. TTE results analysis showed that the hyperdynamic LVEF group had higher stroke volume (SV) and cardiac index (CI) than those in the normal LVEF and low LVEF groups, lower systemic vascular resistance (SVR) than that in the normal LVEF and low LVEF groups, and an increased E/A ratio. The 90-day mortality in the hyperdynamic LVEF group was significantly higher than that in the normal LVEF and low LVEF groups [59.1% (26/44) vs. 24.9% (42/169), 32.5% (13/40), both P < 0.05]. Multivariate Logistic regression analysis showed that chronic liver disease [odds ratio (OR) = 1.712, 95% confidence interval (95%CI) was 0.912-3.234, P < 0.001], cancer (OR = 2.784, 95%CI was 1.296-6.151, P < 0.001), HR (OR = 1.026, 95%CI was 1.014-1.038, P < 0.001), vasoactive drug dose (OR = 1.133, 95%CI was 1.009-1.291, P < 0.001), and invasive mechanical ventilation (OR = 2.141, 95%CI was 1.285-3.651, P < 0.001) were independent factors for hyperdynamic LVEF in ICU sepsis patients. Correlation analysis showed that the mortality of hyperdynamic LVEF, normal LVEF and low LVEF patients was positively correlated with vasoactive drug dose (r value was 0.251, 0.361, 0.289, respectively, all P < 0.001). The mortality of the hyperdynamic LVEF patients was negatively correlated with SVR (r = -0.545, P < 0.001). CONCLUSIONS: Chronic liver disease, cancer, HR, vasoactive drugs dose, and invasive mechanical ventilation are independent risk factors for hyperdynamic LVEF in patients with sepsis. Hyperdynamic LVEF is positively associated with mortality in sepsis patients, which may be due to the the decrease of SVR caused by septic vascular paralysis.

[Values of glycemic lability index in the prognostic evaluation of critically ill patients in intensive care unit].

OBJECTIVE: To access the predictive values of glycemic lability index (GLI) as an indicator of glucose variability in the prognosis of critically ill patients. METHODS: A prospective study of 72 critically ill patients admitted into intensive care unit (ICU) were performed. Capillary glucose was measured on admission and every 2 hrs afterward during the first 24 hrs. GLI, mean amplitude of glycemic excursion (MAGE), largest amplitude of glycemic excursions (LAGE), mean, standard deviation (SD) and coefficient of variability (CV) were calculated respectively. The 30 day mortality was selected as the end-point. Receiver operating curve (ROC) was drawn to explore the association between each indicator of glucose variability and prognosis. The subjects were subsequently divided into 4 subgroups according to the median of mean and GLI. The 30-day mortality was then compared between the subgroups. RESULTS: Thirty-one of 72 patients died with a mortality rate of 43.1%. The area under the curve (AUC) of GLI (0.798 ± 0.051) was superior to that of MAGE (0.785 ± 0.053), LAGE (0.772 ± 0.056), SD (0.761 ± 0.056), CV (0.729 ± 0.059) and mean (0.670 ± 0.065) under the determination of ROC respectively. GLI was significantly correlated with APACHE II (acute physiology and chronic health evaluation II) score assessed during the first 24 hrs after admission (R(2) = 0.787, P < 0.001). With the rise of GLI value, the 30-day mortality also increased gradually. Subgroup analysis demonstrated that the duration of mechanical ventilation, the incidence of multiple organ failure (MOF), the utilization rate of CRRT (continuous renal replacement therapy), the staying length of ICU and the 30 mortality rate was (3.3 ± 4.4) d, 41.6%, 12.5%, (4.6 ± 4.5) d and 16.7% respectively in the low mean +low GLI subgroup. They decreased obviously compared to the low mean +high GLI, high mean +low GLI and high mean +high GLI groups. Therefore the low mean +low GLI subgroup had the best prognosis while the high mean +high GLI subgroup worst. CONCLUSION: GLI of the first 24 hrs after ICU admission can serve as an indicator of glucose variability. And it is significantly correlated with the patient prognosis.

[Effect of continuous renal replacement therapy started at different time on patients with multiple organ dysfunction syndrome].

OBJECTIVE: To explore the effects of continuous renal replacement therapy (CRRT) on serum cytokines and prognosis in multiple organ dysfunction syndrome (MODS) patients based on different therapeutic opportunities. METHODS: A total of 34 MODS patients in the treatment of CRRT after admission to ICU of our hospital between July 2008 and October 2010 were recruited. Based on the time interval from the onset of MODS to the initiation of CRRT, the patients were stratified into early group (0 - 3 days, n = 16) and late group (4 - 10 days, n = 18). Both groups of MODS patients received conventional treatment in addition to 72 hours of high-volume hemofiltration (HVHF). The serum levels of such inflammatory mediators as interleukin (IL)-1ß, interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor (TNF)-α, soluble tumor necrosis factor receptor1 (sTNFR1) and IL-10 were detected by enzyme linked immunosorbent assay (ELISA) before CRRT (0 h) and 6, 12, 18, 24, 48 and 72 h during the treatment of CRRT. Dynamic APACHEII scores were also evaluated. RESULTS: (1) The early group had lower serum levels of IL-1ß, IL-6, IL-10 and higher IL-1Ra, L-1Ra/IL-1ß ratio at 72 h than those of 0 h (P < 0.05). And the late group had a declining serum level of IL-1ß, IL-6, TNF-α and IL-10 and a rising ratio of IL-1Ra and IL-1Ra/IL-1ß during the first 24 h (P < 0.05). As compared with the late group, the early group had a lower level of IL-10 [(25 ± 12) vs (51 ± 33) ng/L] and higher ratios of IL-1Ra and IL-1Ra/IL-1ß at 72 h [(1382 ± 899 vs (683 ± 188) ng/L, (54 ± 10) vs (23 ± 6)] (both P < 0.05). (2) The early group had a lower APACHEIIscore than the late group at 0 h (P < 0.05). APACHEII score at 72 h was significantly lower than 0 h in the early group. And there was no obvious change in the late group. There was no statistical difference in the numbers of MODS patients with dysfunctional organs number ≥ 4 at 0 h in both groups. The number of MODS patients with dysfunctional organs number ≥ 4 at 72 h was lower than 0 h in the early group (P < 0.05). And there was no statistical difference in the late group. CONCLUSION: Regulating the ratio of anti-inflammatory/pro-inflammatory mediators is critical in the immunomodulation of CRRT. And CRRT may provide more clinical benefits in the early phase (0 - 3 days) of MODS.

Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.

PURPOSE: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure. METHODS: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality. RESULTS: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies. CONCLUSIONS: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

[Application of continuous veno-venous hemofiltration in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the changes of interleukin (IL)-6 serum level in patients with acute respiratory distress syndrome (ARDS) and the effects of continuous renal replacement therapy (CRRT) on IL-6 level and its clinical significance. METHODS: Forty ARDS patients were randomly divided into 2 equal groups: Group A undergoing conventional treatment and Group B receiving conventional treatment plus CRRT at onset of ARDS. Serum IL-6 level was measured by enzyme linked immunosorbent assay (ELISA) at the onset (0 h) and 12, 24, 48, and 72 hours later. Dynamic APACHEII score was also evaluated at the time points of 0, 24, 48, and 72 h. The incidence of ventilator-associated pneumonia (VAP), intensive care unit (ICU) mortality rate, duration of total mechanical ventilation, and ICU stay were assessed. Twenty-five healthy examinees were used as controls. RESULTS: The serum IL-6 level of the whole ARDS patients was significantly higher then that of the normal controls (P < 0.01), and the serum IL-6 level of the ARDS patients who died was significantly higher than that of the ARDS patients who survived (P < 0.01). The IL-6 serum level was correlated well with the APACHEIIscore either in the survival subgroup or the non-survival subgroup (for the former: r = 0.560 P = 0.008, and for the latter: r = 0.518 P = 0.023). Group B, contrary to Group A, had persistently decreased serum IL-6 levels and APACHEII scores at the onset and during the progression of ARDS (all P < 0.05). The incidence of VAP in Group B was 45%, significantly lower than that in Group A (80%, P = 0.022) while the ICU mortality rate didn't differ between the two groups (40% vs 55%, P = 0.342). The duration of total mechanical ventilation and ICU stay of the Group B patients who underwent early CRRT were (12 +/- 5) days and (16 +/- 5) days respectively, both significantly shorter than those of Group A patients [(16 +/- 5) days, P = 0.027 and (19 +/- 5) days, P = 0.030]. CONCLUSION: The elevated serum IL-6 level in ARDS patients seems to be correlated well with the severity of lung injury, and appears to be a good marker to judge the prognosis of the disease combined with APACHEII score. In the early phase of ARDS, CRRT can decrease the high serum level of IL-6, shorten the duration of total mechanical ventilation and ICU stay, and decrease the incidence of VAP. Removal of the circulating proinflammatory cytokines by CRRT may be one of the most vital mechanisms to treat ARDS.

dbLGL: an online leukemia gene and literature database for the retrospective comparison of adult and childhood leukemia genetics with literature evidence.

Leukemia is a group of cancers with increased numbers of immature or abnormal leucocytes that originated in the bone marrow and other blood-forming organs. The development of differentially diagnostic biomarkers for different subtypes largely depends on understanding the biological pathways and regulatory mechanisms associated with leukemia-implicated genes. Unfortunately, the leukemia-implicated genes that have been identified thus far are scattered among thousands of published studies, and no systematic summary of the differences between adult and childhood leukemia exists with regard to the causative genetic mutations and genetic mechanisms of the various subtypes. In this study, we performed a systematic literature review of those susceptibility genes reported in small-scale experiments and built an online gene database containing a total of 1805 leukemia-associated genes, available at http://soft.bioinfo-minzhao.org/lgl/. Our comparison of genes from the four primary subtypes and between adult and childhood cases identified a number of potential genes related to patient survival. These curated genes can satisfy a growing demand for further integrating genomics screening for leukemia-associated low-frequency mutated genes.Database URL: http://soft.bioinfo-minzhao.org/lgl/.

[Value of procalcitonin on predicting the severity and prognosis in patients with early ARDS: a prospective observation study].

OBJECTIVE: To investigate the value of procalcitonin (PCT) on predicting the severity and prognosis in patients with early acute respiratory distress syndrome (ARDS). METHODS: A prospective observation study was conducted. A total of 113 patients with ARDS undergoing mechanical ventilation admitted to intensive care unit (ICU) of Affiliated People's Hospital of Jiangsu University from October 2012 to April 2016 were enrolled. Based on oxygenation index (PaO2/FiO2), the patients were classified into mild, moderate, and severe groups according to Berlin Definition. Twenty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score, and Murray lung injury score were recorded. Within 24 hours after diagnosis of ARDS, the serum levels of PCT and C-reactive protein (CRP) were determined by enzyme-linked fluorescence analysis (ELFA) and immune turbidimetric method, respectively. The patients were also divided into survival and non-survival groups according to clinical outcome within 28-day follow-up, and the clinical data were compared between the two groups. Spearman rank correlation was applied to determine the correlation between variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic curve (ROC). Kaplan-Meier survival curve analysis was used to compare different PCT levels of patients with 28-day cumulative survival rate. RESULTS: After excluding patients who did not meet the inclusion criteria and loss to follow-up, the final 89 patients were enrolled in the analysis. Among 89 ARDS patients analyzed, 27 of them were mild, 34 moderate, and 28 severe ARDS. No significant differences were found in age and gender between ARDS and healthy control groups. Infection and trauma were the most common etiology of ARDS (55.1% and 34.8%, respectively). Compared with healthy control group, both CRP and PCT in serum of ARDS group were higher [CRP (mg/L): 146.32 (111.31, 168.49) vs. 6.08 (4.47, 7.89), PCT (µg/L): 3.46 (1.98, 5.56) vs. 0.02 (0.01, 0.04), both P < 0.01], and the two showed sustained upward trends with the ARDS course of disease. Compared with mild group, severe group had significantly higher APACHE II and Murray scores. Spearman rank correlation analysis showed that both serum PCT and CRP in patients with ARDS was correlated well with APACHE II score (r values were 0.669 and 0.601, respectively, both P < 0.001), while PCT was weakly but positively correlated with Murray score (r = 0.294, P = 0.005), but not the case of CRP (r = 0.203, P = 0.052). APACHE II score and serum PCT in non-survival group (n = 38) were significantly higher than those of the survival group [n = 51; APACHE II score: 26.00 (23.00, 28.50) vs. 21.00 (17.00, 25.00), PCT (µg/L): 6.38 (2.82, 9.49) vs. 3.09 (1.08, 3.57), both P < 0.01], but Murray score and CRP level were similar between survivors and non-survivors. The areas under ROC curve (AUC) of APACHE II score and PCT for predicting 28-day mortality were 0.781 and 0.793, respectively, which were better than those of AUC of Murray score and CRP (0.606 and 0.561, respectively, all P < 0.05). The AUC of APACHE II score combined with PCT was significantly higher than that of PCT (0.859 vs. 0.793, P = 0.048) or APACHE II score alone (0.859 vs. 0.781, P = 0.038). Using a PCT cut-off value of > 4.35 µg/L for predicting 28-day mortality, the sensitivity and specificity was 92.2% and 63.2%, respectively, and the positive and negative likelihood ratios were 2.50 and 0.12 respectively. Kaplan-Meier survival curve analysis indicated that the patients whose PCT more than 4.35 µg/L, had lower 28-day cummulative survival rate as compared with those with PCT ≤ 4.35 µg/L (log-rank test: χ2 = 5.013, P = 0.025). CONCLUSIONS: The elevated serum PCT level in patients with ARDS seems to be correlated well with the severity of lung injury, and appears to be a useful prognostic marker of outcome in the early phases of ARDS.

[Clinical study of the influence of daily sedation interruption on fluctuation of blood glucose level and mortality of critical patients with multiple trauma].

OBJECTIVE: To assess the influence of a protocol of routine daily interruption of sedation on fluctuation of blood glucose level and mortality of critical patients with multiple trauma. METHODS: A prospective study involving 68 critical patients with multiple trauma admitted to intensive care unit (ICU) was performed. Finger blood glucose level was measured after the implementation of daily interruption of sedation, and the results were recorded every 2 hours during the first 24 hours. Mean (MEAN), standard deviation (SD) and coefficient of variability (CV) of blood glucose level, glycemic liability index (GLI), mean amplitude of glycemic excursion (MAGE) and largest amplitude of glycemic excursions (LAGE) were calculated respectively, and 30-day mortality was recorded. The patients under study were divided into four groups according to the median values of MEAN and GLI, group A with patients of low MEAN+low GLI (n=34), group B with patients of low MEAN+high GLI (n=14), group C with patients of high MEAN+low GLI (n=12), and group D with patients of high MEAN+high GLI (n=8). Glucose levels, their range of fluctuation, and the prognosis were compared among groups. RESULTS: Five of the 68 patients died, with a gross mortality rate of 7.4%. Group analysis demonstrated that the patients in group A had the best prognosis with the 30-day mortality rate of 0 (0/34), while that of the group D was worst with the 30-day mortality rate of 37.5% (3/8). The MEAN levels of glucose were relatively lower in groups A and B (6.7±1.3 mmol/L, 7.6±0.8 mmol/L) and higher in groups C and D (9.3±1.4 mmol/L, 10.7±1.3 mmol/L). Indicators of glucose level fluctuation, including SD, CV, GLI, LAGE, and MAGE, were lower in groups A and C (SD: 1.6±0.4 mmol/L, 1.7±0.6 mmol/L; CV: 0.2±0.1, 0.2±0.1; GLI: 26.5±19.5, 40.1±17.6; LAGE: 4.6±2.3 mmol/L, 6.5±1.9 mmol/L; MAGE: 2.7±0.8 mmol/L, 3.1±0.80 mmol/L), and higher in groups B and D (SD: 2.9±0.7 mmol/L, 3.9±0.8 mmol/L; CV: 0.4±0.1, 0.4±0.1; GLI: 120.5±33.2, 184.6±98.4; LAGE: 9.5±2.0 mmol/L, 12.7±4.0 mmol/L; MAGE: 6.2±1.2 mmol/L, 7.6±1.8 mmol/L). The incidence of hypoglycemia was highest in group D [5.8% (6/104)], followed by that of group B [1.6% (3/182)], while that of groups A and C was lower [0.9% (4/442), 0.1% (2/256)]. The incidence of hyperglycemia were highest in groups C and D [67.3% (105/156), 69.2% (72/104)], and it was followed by that of group B [33.5% (61/182)], and that of group A was the lowest [15.4% (68/442)]. The duration of mechanical ventilation [(3.4±3.3) days], the incidence of multiple organ failure (MOF, 44.1%, 15/34), rate of continuous renal replacement therapy (CRRT, 11.8%, 4/34), and day in ICU [(5.1±3.9) days] were shortest and lowest in group A, and highest and longest in group D [(9.4±5.2) days, 87.5% (7/8), 75.0% (4/8), (10.3±7.4) days]. CONCLUSIONS: Daily interruption of sedation can reduce fluctuation of blood glucose level in critical patients with multiple trauma, and improve patients' outcome.

Kinetic analysis of the immunity in a pregnant patient infected with avian influenza H7N9.

BACKGROUND: Human infection with avian influenza A H7N9 has emerged in China since February, 2013. The immunologic changes in pregnant women infected with H7N9 are not known. OBJECTIVE: To report the clinical data and kinetic changes of immunity in a pregnant woman infected with H7N9 virus in Zhenjiang, Jiangsu, China. METHODS: The clinical data were collected and immunity status was monitored in this patient. RESULTS: H7N9 virus became undetectable in sputum from 14 days since onset of symptoms after effective antiviral therapy with oseltamivir and symptomatic/supporting treatments. The symptoms and signs in this patient gradually improved from 15 days since onset of symptoms. Peripheral lymphocytes initially decreased and gradually increased. The percentage of CD4+ T cells increased since 16 days after onset of symptoms. The kinetic changes of cytokines including IFN-γ, IFN-α, TNF-α, IL-10 and TGF-ß1 matched the development and recovery of illness. Her family members, including her parents exposed to H7N9 positive materials in poultry market, were H7N9 negative. CONCLUSIONS: Our results indicate that pregnant women are susceptible to H7N9 virus and H7N9 infection in pregnant women is curable without significant impact on fetus. Kinetic changes of pro-inflammatory and anti-inflammatory cytokines play a role in the pathogenesis and clinical outcome in the pregnant patient with H7N9 infection.

Value of serum procalcitonin in evaluating the prognosis of sepsis in elderly patients with colorectal cancer undergoing emergency colorectal surgery.

Serum procalcitonin (PCT) levels may have predictive value in the prognosis of postoperative sepsis in elderly patients who have undergone colorectal surgery for colorectal cancer in intensive care units (ICUs). A prospective study involving 90 critically ill patients who underwent colorectal surgery for colorectal cancer in ICUs was performed. Twenty-eight patients were diagnosed with sepsis, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria, and these patients were included in the sepsis group. Sixty-two patients, who were without evidence of sepsis, were enrolled in the control group. We measured the serum PCT concentrations preoperatively (immediately before induction of anesthesia), upon arrival in the ICU (ICU day 0), on the morning of the first postoperative day (postoperative day 1), and on the morning of the third postoperative day (postoperative day 3). The C-reactive protein (CRP) index, acute physiology and chronic health evaluation II (APACHE II) score, mechanical duration of ventilation, mortality rate, incidence of multiple organ failure, and usage of continuous renal replacement therapy were evaluated. The area under the curve for the receiver operating characteristic curve (AUC-ROCC) was measured to explore the association between the serum PCT and the prognosis. In the sepsis group, 12/28 patients died (mortality rate 43 %). In the control group, 6/62 patients died (mortality rate 9.7 %). On the first postoperative day, the serum PCT level was dramatically higher in the sepsis group than in the control group (2.71 ± 1.13 vs. 1.37 ± 0.57, P ≤ 0.05). The PCT level on the first postoperative day was distinctly higher than that measured upon arrival in the ICU (2.71 ± 1.13 vs. 1.31 ± 0.58, P ≤ 0.05). In the two groups, the CRP concentrations were both markedly higher on the first postoperative day than upon arrival in the ICU (138.89 ± 45.12 vs. 70.43 ± 23.54 in the sepsis group, and 133.13 ± 44.91 vs. 69.65 ± 24.98 in the control group, P ≤ 0.05). Linear regression analysis was performed. The results suggest that the PCT and APACHE-II scores were not significantly associated. On the first and third postoperative days, the PCT levels were associated with increased odds of sepsis (AUC-ROCC, 95 % confidence interval 0.817-0.973, P = 0.000, and 0.755-0.944, P = 0.000, respectively). The outcomes of patients in the sepsis group were worse than those in the control group. PCT levels appear to be early markers of postoperative sepsis in elderly patients undergoing colorectal surgery for colorectal cancer during the ICU course. These findings could allow for early identification of postoperative septic complications and be used for prognostic evaluation of these patients.