A therapeutic regimen of ceftazidime-avibactam for a critical patient receiving prolonged intermittent renal replacement therapy.

The present report firstly described a critically ill patient receiving a dosing regimen of ceftazidime-avibactam (CAZ-AVI) (1.875g q24h) to eliminate multidrug-resistant Klebsiella pneumoniae and a scheduled time for prolonged intermittent renal replacement therapy (PIRRT) every 48h (6h-session beginning 12h after the previous dosage on hemodialysis day). This dosing regimen for CAZ-AVI and a scheduled time for PIRRT allowed pharmacodynamic parameters of ceftazidime and avibactam to have little difference on hemodialysis and non-hemodialysis days so that we can maintain a relatively stable drug concentration. Our report highlighted not only the importance of dosing regimens in patients with PIRRT but also the significance of hemodialysis time points during the dosing interval. The innovative therapeutic plan proved to be suitable for patients infected with Klebsiella pneumoniae when on PIRRT according to the trough plasma concentrations of ceftazidime and avibactam which were maintained above the minimum inhibitory concentration during the dosing interval.

Treatment of traumatic cerebrospinal fluid rhinorrhea via extended extradural anterior skull base approach.

OBJECTIVE: To describe and assess the repair technique and perioperative management for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture via extradural anterior skull base approach. METHODS: This was a retrospective review conducted at the Department of Neurosurgery of the Shanghai Tenth People's Hospital from January 2015 to April 2020. Patients with traumatic CSF rhinorrhea resulting from extensive anterior skull base fracture treated surgically via extended extradural anterior skull base approach were included in this study. The data of medical and radiological records, surgical approaches, repair techniques, peritoperative management, surgical outcome and postoperative follow-up were analyzed. Surgical repair techniques were tailored to the condition of associated injuries of the scalp, bony and dura injuries and associated intracranial lesions. Patients were followed up for the outcome of CSF leak and surgical complications. Data were presented as frequency and percent. RESULTS: Thirty-five patients were included in this series. The patients' mean age was 33 years (range 11-71 years). Eight patients were treated surgically within 2 weeks; while the other 27 patients, with prolonged or recurrent CSF rhinorrhea, received the repair surgery at 17 days to 10 years after the initial trauma. The mean overall length of follow-up was 23 months (range 3-65 months). All the patients suffered from frontobasal multiple fractures. The basic repair tenet was to achieve watertight seal of the dura. The frontal pericranial flap alone was used in 20 patients, combined with temporalis muscle and/or its facia in 10 patients. Free fascia lata graft was used instead in the rest 5 patients. No CSF leak was found in all the patients at discharge. There was no surgical mortality in this series. Bilateral anosmia was the most common complication. At follow-up, no recurrent CSF leak or meningitis occurred. No patients developed mucoceles, epidural abscess or osteomyelitis. One patient ultimately required ventriculoperitoneal shunt because of progressive hydrocephalus. CONCLUSION: Traumatic CSF rhinorrhea associated with extensive anterior skull base fractures often requires aggressive treatment via extended intracranial extradural approach. Vascularized tissue flaps are ideal grafts for cranial base reconstruction, either alone or in combination with temporalis muscle and its fascia---fascia lata sometimes can be opted as free autologous graft. The approach is usually reserved for patients with traumatic CSF rhinorrhea in complex frontobasal injuries.

Dexmedetomidine alleviates doxorubicin cardiotoxicity by inhibiting mitochondrial reactive oxygen species generation.

Cardiotoxicity largely limits the application of doxorubicin (Dox) for cancer treatment. Dexmedetomidine (Dex), a selective agonist of α2-adrenergic receptor, has been suggested to exert cardioprotection against myocardial injury. However, the effect and underlying mechanisms of Dex on Dox cardiotoxicity remain unknown. In this study, C57BL/6 mice were treated with Dox followed by Dex administration. Cardiomyocytes were co-incubated with Dox and Dex in vitro. The results showed that Dex markedly attenuated cardiac dysfunction induced by Dox. TUNEL staining exhibited that Dex inhibited Dox-induced cardiomyocyte apoptosis in myocardium. Moreover, the expression of anti-apoptotic protein Bcl-2 was increased, whereas the expression of pro-apoptotic protein Bax was decreased by Dex. Dox-induced the increase of reactive oxygen species (ROS), superoxide anion, and mitochondrial ROS (mROS) generation in myocardial tissues were significantly inhibited after Dex administration. In in vitro study, it was further confirmed that Dex prevented Dox-induced cardiomyocyte apoptosis and injury. However, the stimulation of mROS generation reversed the effect of Dex in cardiomyocytes. Mechanically, Dex blocked Dox-induced the ubiquitination of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), leading to the restoration of PGC-1α and downstream oxidative stress-protective molecules uncoupling protein 2 and manganese-dependent superoxide dismutase expression. Taken together, this study demonstrates that Dex exerts cardioprotection against Dox cardiotoxicity by attenuating mitochondrial dysfunction, oxidative stress, and cardiomyocyte apoptosis via inhibiting PGC-1α-signaling pathway inactivation. This suggests that Dex may be a potential therapeutic strategy for Dox cardiotoxicity treatment.

Gene expression profile of the hippocampus of rats subjected to traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival-related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival-related genes in the hippocampus by using real-time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

Value of Kidney Disease Improving Global Outcomes Urine Output Criteria in Critically Ill Patients: A Secondary Analysis of a Multicenter Prospective Cohort Study.

BACKGROUND: Urine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr). METHODS: We conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses. RESULTS: The prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality. CONCLUSION: UO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Prevalence, risk factors, clinical course, and outcome of acute kidney injury in Chinese intensive care units: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) has been recognized as a major healthcare problem affecting millions of patients worldwide. However, epidemiologic data concerning AKI in China are still lacking. The objectives of this study were to characterize AKI defined by RIFLE criteria, assess the association with hospital mortality, and evaluate the impact of AKI in the context of other risk factors. METHODS: This prospective multicenter observational study enrolled 3,063 consecutive patients from 1 July 2009 to 31 August 2009 in 22 ICUs across mainland China. We excluded patients who were admitted for less than 24 hours (n = 1623), younger than 18 years (n = 127), receiving chronic hemodialysis (n = 29), receiving renal transplantation (n = 1) and unknown reasons (n = 28). There were 1255 patients in the final analysis. AKI was diagnosed and classified according to RIFLE criteria. RESULTS: There were 396 patients (31.6%) who had AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91 (7.3%), and 179 (14.3%) patients, respectively. Renal function deteriorated in 206 patients (16.4%). In comparison with non AKI patients, patients in the risk class on ICU admission were more likely to progress to the injury class (odds ratio (OR) 3.564, 95% confidence interval (CI) 1.706 - 7.443, P = 0.001], while patients in the risk class (OR 5.215, 95% CI 2.798-9.719, P < 0.001) and injury class (OR 13.316, 95% CI 7.507-23.622, P < 0.001) had a significantly higher probability of deteriorating into failure class. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group. CONCLUSIONS: The prevalence of AKI was high among critically ill patients in Chinese ICUs. In comparison with non-AKI patients, patients with RIFLE class R or class I on ICU admission were more susceptibility to progression to class I or class F. The RIFLE criteria were robust and correlated well with clinical deterioration and mortality.

Endothelial cell injury with inflammatory cytokine and coagulation in patients with sepsis.

BACKGROUND: Current studies on CD62P have focused mainly on cardiovascular diseases, while only few studies have evaluated the effects of CD62P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation. This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P (s-CD62P) in plasma and its mechanism in patients with sepsis, thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62P. METHODS: A total of 70 critically ill patients with systemic inflammatory response syndrome (SIRS) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrolled for a prospective and control study. According to the diagnostic criteria of sepsis/SIRS, the patients were divided into two groups: a sepsis group (n=38) and a SIRS group (n=32). Another 20 healthy volunteers served as a control group. Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure, diabetes and its complications. The demographics of the patients including age, sex, body mass index (BMI), smoking and alcohol addict were compared among the groups. Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P, TNF-α, and hs-CRP. And variables of coagulation function such as platelet (PLT), prothrombin (PT), activated partial thromboplastin time (APTT), D-dimer and antithrombin-III (AT-III) were analyzed during 24 hours after admission to ICU. Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated. Data were expressed as mean±standard deviation and were statistically analyzed by using SPSS 17.0 statistical software. The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test. The relations between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis. Changes were considered as statistically significant if P value was less than 0.05. RESULTS: Compared with the control group and SIRS group, the sepsis group demonstrated significantly higher levels of s-CD62P, TNF-α and highly sensitive C-reactive protein (hs-CRP) (P<0.05). The plasma levels of D-dimer, PT, and APTT in the sepsis and SIRS groups were significantly higher than those in the control group, while the platelet count and the activity of AT-III were obviously lower (P<0.05). In the sepsis group, the plasma levels of hs-CRP and TNF-α were positively correlated with PT, APTT, and D-dimer, and negatively correlated with AT-III and PLT (P<0.05). The plasma levels of s-CD62P were significantly correlated with the plasma levels of TNF-α, hs-CRP, D-dimer, PT, and APTT, whereas they were correlated negatively well with PLT and AT-III (P<0.05). CONCLUSIONS: The concentration of plasma s-CD62P is elevated as a early biomarker in patients with sepsis, and it serves as one of the pathogenic factors responsible for endothelial cell damage. Coagulation and mediators of inflammation promote each other, aggravating the severity of sepsis. Plasma s-CD62P may be an important factor for the development of coagulation and inflammatory reaction.

[Evaluation of accuracy and influence factors of bedside blood glucose monitoring in critically ill patients].

OBJECTIVE: To evaluate the accuracy and influence factors of point-of-care testing (POCT) for glucose in critically ill patients. METHODS: Two hundred and forty critically ill patients aged ≥18 years in department of critical care medicine were enrolled. According to blood glucose level (BGL) during glucose control, patients were divided into three groups: (1) hypoglycemia group, BGL<4.5 mmol/L, n=32; (2) euglycemia group, BGL 4.5-8.3 mmol/L, n=138; (3) hyperglycemia group, BGL>8.3 mmol/L, n=70. The blood samples from vein, artery and capillary of patients were collected synchronically and the blood glucose of POCT were determined with glucose oxidase (GOD) and glucose dehydrogenase (GDH) methods, respectively, compared with blood glucose reference values of laboratory [hexokinase method (HK method)]. The accuracy of POCT for glucose and influence factors were analyzed statistically by the logistic regression method. RESULTS: (1) The inaccurate rates of glucose values in blood samples from vein, artery and capillary in hypoglycemia group (GDH method: 25.00%, 40.62%, 40.62%; GOD method: 59.38%, 71.88%, 71.88%) were significantly higher than those in euglycemia group (GDH method: 2.90%, 9.42%, 7.97%; GOD method: 18.12%, 27.54%, 27.54%) and hyperglycemia group (GDH method: 1.43%, 8.57%, 4.28%; GOD method: 11.43%, 8.57%, 11.43%, all P<0.01). (2) The average levels of difference for the glucose reference value of laboratory and the glucose value measured by glucometer in hypoglycemia group were 0.41-0.69 mmol/L (GDH method) and 0.92-1.18 mmol/L (GOD method), in euglycemia 0.16-0.33 mmol/L and 0.77-0.90 mmol/L, in hyperglycemia group -0.06-0.18 mmol/L and 0.56-0.76 mmol/L, respectively. (3) The correlation coefficients between the laboratory and glucometer in hypoglycemia group were respectively 0.812-0.853 (GDH method) and 0.723-0.816 (GOD method). The correlation coefficients in euglycemia group were 0.862-0.890 and 0.768-0.857. They were elevated to 0.922-0.957 and 0.896-0.922 in hyperglycemia group (all P<0.01). (4)On the influence factors of accuracy in POCT for glucose, BGL, acute physiology and chronic health evaluation II (APACHEII) score and hematocrit level were into the logistic regression equation. CONCLUSIONS: The accuracy of POCT for glucose was markedly affected by the BGL, severity of patients and hematocrit level during glucose control. Under hypoglycemia, the agreement between laboratory and glucometer measurements was obviously fallen and it tended to overestimate the patient's real glucose value.

[Effects and mechanisms of heme oxygenase-1 on rats with postresuscitation myocardial dysfunction].

OBJECTIVE: To explore the effects and mechanisms of heme oxygenase-1 on rats with postresuscitation myocardial dysfunction. METHODS: Male Sprague-Dawley rats were asphyxiated for 9 minutes and resuscitated. They were randomly divided into 4 groups: sham-operated, cardiopulmonary resuscitation (CPR), hemin and hemin + ZnPP (zinc protoporphyrin IX). Resuscitated groups had 2 observation points: 6 and 24 hours post-CPR (n = 8 for each time point). And the sham-operated group of 12 rats were divided in two observation points, according to 6 or 24 hours post-operation (n = 6 each). Hemodynamic was observed. The expression of heme oxygenase-1 (HO-1) in cardiac tissue was detected by Western blot. And the activity of cardiac homogenate superoxide dismutase (SOD) was determined by xanthine oxidase method and the level of malondialdehyde (MDA) measured by the thiobarbituric acid method. Nitrotyrosine protein expression in cardiac tissue was analyzed by immunohistochemistry. RESULTS: (1) The mean blood pressure (MAP) significantly decreased in resuscitated groups after resuscitation (all P < 0.05). No difference existed between the subgroups. The scores of dP/dt40 and -dP/dt significantly decreased in CPR and hemin + ZnPP groups after resuscitation (all P < 0.05). But dP/dt40 in hemin group did not differ significantly after resuscitation and -dP/dt decreased only 0.5 hour and 1 hour post-resuscitation (3341.60 ± 524.85 and 3711.40 ± 502.39 vs 4284.20 ± 800.87, all P < 0.05). The scores of dP/dt40 and -dP/dt in hemin group at all time points post-resuscitation were significantly higher than those in CPR and hemin + ZnPP groups (all P < 0.05). (2) Compared with the sham-operated group, the HO-1 expression, MDA level and nitrotyrosine protein expression significantly increased while the activities of SOD decreased after resuscitation in the CPR, hemin and hemin + ZnPP groups (all P < 0.05). Compared with the CPR and hemin + ZnPP groups, the expression of HO-1 and the activity of SOD increased, while MDA level and nitrotyrosine protein expression were decreased in group hemin (all P < 0.05). No difference existed in the above indices between the CPR and hemin + ZnPP groups. CONCLUSION: HO-1 can reduce myocardial oxidative stress injury after cardiopulmonary resuscitation and effectively improve post-resuscitation myocardial function in rats.

[An investigation of the relationship of inflammatory response and insulin and its components during stress hyperglycemia in critically ill patients].

OBJECTIVE: To observe the relationship between inflammatory response and the constituents of islet ß cell secretion during stress hyperglycemia (SHG) in critically ill patients, in order to study the impact of inflammatory response on insulin resistance and the secretion function of islet ß cells. METHODS: According to the state of inflammatory response, 45 critical patients with SHG were divided into two groups: stress and the convalescence period. Twenty five healthy individuals were enrolled as control group. The blood levels of tumour necrosis factor ß (TNF-ß), blood glucose (BG), and insulin components including proinsulin (PI), immunoreactive insulin (IRI), true insulin (TI), C-peptide (C-P) were measured respectively. The levels of BG, TNF-ß, insulin components, insulin resistance index (HOMA-IR) and the secretion index (HOMA-ß) were compared among groups. The relationship between TNF-ß and BG, insulin components, HOMA-IR, HOMA-ß were analyzed. RESULTS: (1)There was no difference in concentrations of TI among stress period, convalescence stage and control group [3.68 (1.57, 7.70), 3.42 (2.41, 7.40), 1.46 (0.35, 4.90) mU/L, all P >0.05], whereas the concentration of BG [(10.04 ± 2.43) mmol/L], TNF-ß [13.70 (11.77, 20.00) ng/L], PI [6.20 (3.22, 9.27) pmol/L], IRI [13.45 (9.88, 19.88) mU/L] and C-P [3.01 (2.37, 4.00) µg/L]in stress period were significantly higher than those in the convalescence stage[BG: (6.09 ± 0.84) mmol/L, TNF-ß: 11.58 (8.80, 13.22) ng/L,PI: 1.54 (0.36, 11.82) pmol/L, IRI: 10.80 (5.35, 12.60) mU/L, C-P: 2.42 (1.17, 3.56) µg/L] and control group [BG: (4.87 ± 0.56) mmol/L,TNF-ß: 9.27 (7.48, 12.16) ng/L, PI: 2.20 (1.88, 4.54) pmol/L, IRI: 5.50 (4.00, 8.00) mU/L, C-P: 1.15 (0.87, 1.76) µg/L, P <0.05 or P <0.01]. (2)The HOMA-IR [5.17 (3.41, 11.51)] in stress period was significantly higher than that in the convalescence[3.24 (1.51, 6.95)] and control group [1.14 (0.81, 1.79), P <0.05 and P<0.01]. The HOMA-ß [10.80 (3.72, 31.40)] of isletß cell in stress period was significantly lower than that in the convalescence [28.42 (6.46, 125.01)] and control group [21.94 (7.77, 62.01), P <0.01 and P <0.05]. (3)There were positive correlations between the concentration of TNF-ß and PI, IRI, C-P and HOMA-IR ( r 1=0.292, r 2=0.344, r 3=0.397, r 4=0.324, P <0.05 or P <0.01). There were negative correlation between concentration of TNF-ß and HOMA-ß ( r =-0.235 , P <0.05) . CONCLUSION: The severer the inflammatory response, the higher PI, IRI and C-P, while the secretion of TI is relatively deficient.Inflammatory response could affect insulin resistance and the secretion function of islet ßcell during SHG in critically ill patients.

[Comparison of computer-driven weaning and physician-directed weaning from mechanical ventilation: a randomized prospective study].

OBJECTIVE: To evaluate if the computer-driven weaning (CDW) with a closed-loop knowledge-based system introduced in a ventilator is superior to physician-directed weaning (PDW) in difficult-to-wean patients in the intensive care unit (ICU). METHODS: Sixty-two difficult-to-wean patients were randomized into 2 groups: weaning with Smart Care/PS (SC group, n = 32) or with synchronize intermittent mandatory ventilation add positive support ventilation (SP group, n = 30). In the SC group, the automated system titrated pressure support, conducted a spontaneous breathing trial and provided notification of success (separation potential). In the SP group, weaning from ventilators was carried out by gradually decreasing respiratory support. The length of mechanical ventilation and stay in ICU, the rate of ventilator-associated pneumonia (VAP), the retubing rate in 48 h, manual ventilator setting changes before extubation were compared between the 2 groups. RESULTS: In the SC group, the weaning time was (49 +/- 13) h, (67 +/- 37) h, and (254 +/- 96) h, respectively in patients with neuromuscular diseases, for post-operative respiratory support and patients with respiratory diseases; while in the SP group, the weaning time was (223 +/- 38) h, (106 +/- 34) h and (502 +/- 91) h, respectively; the difference between the 2 groups being statistically significant (chi(2) = 8.33, 4.77, 4.43, all P < 0.05). The time of stay in ICU was (9.0 +/- 1.7) d and (7.3 +/- 1.9) d in the SC group for patients with neuromuscular diseases and patients with post-operative respiratory support, respectively, while that was (20.8 +/- 5.1) d and (14.6 +/- 1.7) d in the SP group, respectively. Time of stay in ICU was significantly shorter in the SC group (chi2 = 6.74, 7.68, both P < 0.05). The number of manual ventilator setting changes was (5 +/- 1) times in the SC group, significantly less than that of the SP group (13 +/- 3, t = 2.73, P < 0.05). There were no significant differences between the SC and the SP groups in the rate of re-intubation, the rate of tracheotomy, the incidence of pneumothorax, the incidence of VAP and the incidence of subcutaneous emphysema. CONCLUSION: The CDW method used in patients with difficult weaning from ventilators was shown to shorten the weaning time, reduce stay in ICU, and decrease the need for manual adjustment of ventilators.

[Study of relationship between stress hyperglycemia and insulin-resistance related factors].

OBJECTIVE: To observe related factors in the stress hyperglycemia (SHG) of critical illness and to investigate possible pathogenesis of insulin-resistance (IR). METHODS: Blood glucose (BG), insulin (INS), C-peptide (C-P), cortisol (Cor), somatostatin (SS), glucagon (Gluc), tumor necrosis factor-alpha (TNF-alpha),soluble tumor necrosis factor receptor I (sTNFRI) and sTNFRII were determined respectively by radioimmunoassay (RIA) or enzyme linked immunoadsorbent assay (ELISA) in 47 SHG patients with critical illness and 15 healthy volunteers serving as normal controls. Their insulin sensitivity index (ISI) was calculated. RESULTS: (1)Eleven of 47 patients died, while 36 cases survived. Mean acute pathology and chronic health evaluation II (APACHEII) was (13.89+/-6.29) scores within 24 hours after admission to intensive care unit (ICU), mean days of stay in ICU was (5.5+/-6.3) days,and mean duration of mechanical ventilation (MV) was (51.49+/-66.01) hours. (2)The concentrations of INS, ISI, C-P, Cor, Gluc, TNF-alpha, sTNFRI and sTNFRII in 47 SHG patients with critical illness were significantly higher than those in normal controls, except for SS, the differences among groups were significant (P<0.05 or P<0.01). (3)The results of analysis of severity of SHG showed that the more severe SHG was, the higher C-P and INS were, and the less prominent ISI was. (4)Analysis of scores of APACHEII in 47 cases of SHG showed that BG was not increased, but duration of MV, Cor, Gluc, SS, TNF-alpha, sTNFRI and sTNFRII were significantly increased with higher scores of APACHEII. (5)The effect of SHG was significant on MV (F=10.438,P<0.01), but not significant for outcome and days of stay in ICU. (6)The main correlative factors of BG were respectively concentrations of INS (r=0.674, P<0.01), C-P(r=0.552,P<0.01), ISI (r=-0.787, P<0.01), APACHE II(r=0.267,P<0.05) and sTNFRI(r=0.465, P<0.01). CONCLUSION: These results show that main reason of SHG in critical illness is IR. There is no strong significant correlation between acute stress hormones and the level of SHG. sTNFRI has an influence on SHG. However, the over release of TNF-alpha and sTNFRII could be the results of seriousness of the critical illness. There is closely correlation between BG and MV, but not with the age, outcome and days of stay in ICU. The strategy of control and therapy of SHG should be alleviation of stress and improve the utilization of BG in the tissue, and increase sensitivity of INS in the tissue.

[Comparison between bacteriophage-based assay and BACTEC-960 system in detection of ethambutol resistance in Mycobacterium tuberculosis].

OBJECTIVE: To set up phage amplified biologically assay (PhaB) for rapid detection ethambutol (EMB) resistance and to evaluate the use of PhaB in the detection of EMB resistance. METHODS: To detect the EMB resistance of 138 clinical isolates of Mycobacterium tuberculosis (MTB) by PhaB and compare it with the results of BACTEC-960 system. The minimal inhibitory concentration (MIC) was detected for all the discrepant isolates. RESULTS: Of all the 138 strains of MTB clinical isolates, 114 strains were EMB-susceptible and 24 strains were EMB-resistant with BACTEC-960 system while 118 strains were EMB-susceptible and 20 strains were EMB-resistant with PhaB. 112 of the 138 strains were EMB-susceptible and 18 strains were EMB-resistant with the two methods. The concordant isolates in determination of EMB resistance were 130 strains in the two methods and the concordance rate was 94.2%. The disconcordant isolates were 8 strains and the discrepancy rate was 5.8%. The sensitivity, specificity, positive and negative predictive value as well as overall accuracy for the PhaB assay was 75.0% (18/24), 98.2% (112/114), 90.0% (18/20), 94.9% (112/118) and 94.2% (130/138) respectively if the judgment standard was adopted by BACTEC-960 method. CONCLUSIONS: The PhaB assay can be used for detection of EMB resistance in isolates of MTB easily and quickly in three days. This method do not need special instrument and may be used in rapid screening method for EMB resistance of MTB.