[Empirical therapy of bloodstream infections caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae].

OBJECTIVE: To compare the clinical outcomes and costs associated with carbapenems and ß-lactam/ß-lactamase inhibitor combinations (BLBLIs) for the empirical treatment of patients with extended-spectrum ß-lactamase (ESBL)-positive Enterobacteriaceae bloodstream infections (BSIs). METHODS: The medical records of individuals diagnosed with ESBL-producing Escherichia coli and Klebsiella pneumoniae BSIs between January 2014 and June 2015 at Changhai Hospital were reviewed. Patients were divided into two groups based on the empirical therapy (carbapenems group and BLBLIs group). Propensity score matching in a 1∶1 ratio was used to match the patients from two groups. Clinical outcomes and costs were compared before and after matching. RESULTS: One hundred and fifty-eight patients were analyzed, 93 in the carbapenems group and 65 in the BLBLIs group. Before matching, the two groups were significantly different in department distribution, tumor rate, deep vein catheter rate, urinary catheter rate, nasogastric tube rate, and mechanical ventilation rate (all P<0.05), and the carbapenems group had longer total length of stay (LOS) and post-BSI LOS (26.0 vs 18.0 d, P=0.029 and 12.0 vs 10.0 d, P=0.044) , higher hospital cost and daily hospital cost (84 120 vs 39 000 ï¿¥, P<0.001 and 3 451 vs 2 574 ï¿¥, P=0.002). After matching, the two groups had no significant differences in covariates such as sex, age, department distribution, pathogens, comorbidities, invasive interventions, LOS before BSI, multiple admissions, surgical rate during hospitalization and delayed antimicrobial therapy (all P>0.05). Finally, there were no differences between two groups in mortality, post-BSI LOS, total LOS, hospital cost and antimicrobial cost (all P>0.05). CONCLUSION: BLBLIs may provide a reasonable carbapenem-sparing option for the empirical treatment of ESBL producers.

[Impact of extended-spectrum ß-lactamase on clinical outcome and medical cost in patients with bloodstream infection due to Klebsiella pneumoniae].

OBJECTIVE: To evaluate the impact of extended-spectrum ß-lactamase (ESBL) on clinical outcome and medical cost in patients with bloodstream infection (BSI) due to Klebsiella pneumoniae. METHODS: A retrospective study was conducted in patients admitted into Changhai Hospital between January 2013 and December 2014, who suffered from BSI due to Klebsiella pneumoniae during hospitalization. Patients were divided into two groups according to whether Klebsiella pneumoniae produced ESBL (ESBL positive group and ESBL negative group). They were matched with propensity score matching method in a 1∶1 ratio and then multiple regression model was used to analyze the impact of ESBL on clinical outcome and medical cost. Clinical outcome was evaluated by 30-day mortality post BSI; medical cost was evaluated by total length of stay (LOS), post-BSI LOS, total hospital cost and antimicrobial cost. RESULTS: Before matching, the two groups were significantly different in age, nosocomial infection rate, LOS before BSI and surgical rate during hospitalization (all P<0.05). The ESBL-positive group had higher 30-day mortality post BSI (21.3% vs 8.7%, P=0.054), and higher total LOS [25.0(12.0, 33.0) vs 16.0(10.0, 23.0) d, P=0.015], post-BSI LOS [16.0(9.0, 26.0) vs 10.0(5.0, 16.0) d, P=0.006], total hospital cost [69 409(40 605, 198 021) vs 45 683(28 448, 67 000) ï¿¥, P<0.001] and antimicrobial cost [10 279(4 815, 25 500) vs 3 783(1 596, 11 879) ï¿¥, P<0.001]. After matching, the two groups had no significant differences in clinical characteristics such as sex, age, nosocomial infection rate, LOS before BSI, APACHEⅡ score, Charlson Comorbidity Index, underlying diseases and surgical rate during hospitalization (all P>0.05). Multiple regression analysis indicated that ESBL could significantly increase the total LOS, post-BSI LOS, total hospital cost and antimicrobial cost (all P<0.001), but did not increase the 30-day mortality post BSI (P=0.910). CONCLUSIONS: ESBL can significantly increase the medical cost in patients with BSI due to Klebsiella pneumoniae but does not increase the 30-day mortality post BSI.

[One case of atypical septic shock with acute pulmonary edema in a patient with extensive burn].

A 25-year-old man with extensive burn due to industrial dust explosion was admitted to the First Affiliated Hospital of Naval Medical University on 16th October, 2018. Four days after the first skin grafting and vacuum sealing drainage surgery, the patient developed signs of uncontrolled severe inflammation and shock. However, several atypical manifestations interfered the diagnosis of septic shock. After giving emergency treatment including fluid resuscitation, broad-spectrum antibiotics, and administration of vasopressor agents, the patient's condition was alleviated, but quickly relapsed and deteriorated, with acute pulmonary edema appeared in the evening of the same day. Finally, the condition was reversed by completely removing the negative pressure devices on upper limbs and thorough dressing change. This case suggests that the diagnosis and treatment of infection in patients with extensive burn need comprehensive analysis. Timely intervention of the wound is the key to control the exacerbation of sepsis. In addition, the possibility of pulmonary edema in patients with sepsis should be on high alert.

[Comparison of machine learning method and logistic regression model in prediction of acute kidney injury in severely burned patients].

Objective: To build risk prediction models for acute kidney injury (AKI) in severely burned patients, and to compare the prediction performance of machine learning method and logistic regression model. Methods: The clinical data of 157 severely burned patients in August 2nd Kunshan factory aluminum dust explosion accident conforming to the inclusion criteria were collected. Patients suffering AKI within 90 days after admission were enrolled in group AKI, while the others were enrolled in non-AKI group. Single factor analysis was used to choose independent factors associated with AKI, including sex, age, admission time, features of basic injuries, initial score on admission, treatment condition, and mortality on post injury days 30, 60, and 90. Data were processed with Mann-Whitney U test, chi-square test, and Fisher's exact test. Variables with P<0.1 in single factor analysis and those with possible clinical significance were brought into the establishment of prediction model. Logistic regression and XGBoost machine learning algorithm were used to build the prediction model of AKI. The area under receiver operating characteristic curve (AUC) was calculated, and the sensitivity and specificity for optimal threshold value were also calculated for each model. Nonparametric resampling test was used to compare the significance of difference of AUC of the two models. Results: (1) Eighty-nine (56.7%) patients developed AKI within 90 days from admission. Compared with 68 patients in non-AKI group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute physical and chronic health evaluation (APACHE) Ⅱ score, abbreviated burn severity index score, and sequential organ failure assessment (SOFA) score on admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis (χ(2)=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical ventilation, and continuous renal replacement therapy (χ(2)=12.373, 17.201, 43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher mortality on post injury days 30, 60, and 90 (χ(2)=7.483, 37.259, 45.533, P<0.01). There were no statistically significant differences in sex, open decompression, admission time, 24-hour fluid volume after admission, 48-hour fluid volume after admission, the first 24-hour urine volume, the second 24 hour urine volume, the first excision time, and inhalation injury (χ(2)=0.529, 3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of deep vein catheterization of patients in the two groups were both 100%. (2) There were twenty possible prediction variables for preliminary establishment of model according to the difference results of single factor analysis and clinical significance of variables. (3) The logistic regression prediction model had three variables: APACHE Ⅱ score [odds ratio (OR)=1.36, 95% confidence interval (CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the specificity and sensitivity of optimal threshold value 84.4% and 77.7%, respectively. (4) XGBoost machine learning model had seven main predictive variables: APACHE Ⅱ score, full-thickness burn area, 24-hour fluid volume after admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879-0.962), higher than that of logistic regression model (P<0.001), with the specificity and sensitivity of optimal threshold value 89.7% and 82.0%, respectively. Conclusions: Sepsis and fluid resuscitation are two important predictive variables that can be intervened for AKI in severely burned patients. Machine learning method has a better performance and can provide more accurate prediction for individuals than logistic regression prediction model, and therefore has good clinical application prospect.

Epidemiology and outcomes of bloodstream infections in 177 severe burn patients from an industrial disaster: a multicentre retrospective study.

OBJECTIVES: To determine the characteristics of bloodstream infections (BSIs) and to evaluate the impact of BSIs on mortality in severe burn patients. METHODS: A retrospective observational study was conducted in 20 tertiary hospitals. A total of 185 patients who experienced a massive dust explosion in eastern China were included. RESULTS: After exclusion, 177 patients were analysed. The median total body surface area (TBSA) burned was 95% (interquartile range 85%-98%). Inhalation injuries occurred in 97.2%. The overall 90-day mortality was 35% (62/177). During the study period, 120 (67.8%) patients developed 253 episodes of BSI with 323 unique causative pathogens. Sixty-six episodes were polymicrobial infections. Catheter-related BSIs (CRBSIs) accounted for 41.5% of the episodes. Acinetobacter baumannii (19.5%), Klebsiella pneumoniae (13.9%) and Candida (12.7%) were the most common organisms. Antimicrobial resistance was found in 63.5% of the isolates, particularly in Gram-negative bacteria. Patients who developed BSIs had a greater illness severity at admission to the intensive care unit, and worse outcomes. After adjusting for demographics, severity of illness and treatment characteristics in a multivariate logistic model, there was a trend toward BSI increasing the risk of 90-day mortality (adjusted OR 3.4; 95% CI 0.9-12.9; p=0.069). In subgroup analyses, CRBSIs (adjusted OR 5.7; 95% CI 1.3-24.9; p=0.021 versus no BSI) and polymicrobial BSIs (adjusted OR 6.1; 95% CI 1.3-28.1; p=0.020 versus no BSI) had greater risk of 90-day mortality. CONCLUSIONS: A strikingly high rate of BSIs was observed in severe burn patients. Gram-negative organisms and fungi were the leading causes. CRBSIs and polymicrobial BSIs were associated with high mortality.

Patient-reported outcomes of carpal tunnel release surgery in patients with bilateral severe carpal tunnel syndrome.

This retrospective study examined whether the presenting complaint of numbness is relieved post-operatively in severe carpal tunnel syndrome and also assessed any correlation between outcomes of the first and second procedures in staged bilateral carpal tunnel releases. Carpal tunnel release (60 open and 38 endoscopic) was done in 49 patients with bilateral severe carpal tunnel syndrome. There was complete resolution of numbness post-operatively in 77% ( n = 75) of hands. The median post-operative time before complete resolution of numbness was 21 days (IQR 8 to 21; range 3 to 482). The likelihood of complete resolution of symptoms after the second carpal tunnel release in patients with complete resolution of symptoms after the first carpal tunnel release was 22 (95% CI: 4 to 131) times that of the likelihood of improvement in patients with incomplete resolution of symptoms after the first carpal tunnel release. LEVEL OF EVIDENCE: IV.

Long-term outcome of carpal tunnel release surgery in patients with severe carpal tunnel syndrome.

AIMS: Few studies have examined the long-term outcome of carpal tunnel release (CTR). The aim of this study was to evaluate the patient-reported long-term outcome of CTR for electrophysiologically severe carpal tunnel syndrome (CTS). PATIENTS AND METHODS: We reviewed the long-term outcome of 40 patients with bilateral severe CTS who underwent 80 CTRs (46 open, 34 endoscopic) between 2002 and 2012. The outcomes studied were patient-reported outcomes of numbness resolution, the Boston Carpal Tunnel Questionnaire (BCTQ) score, and patient satisfaction. RESULTS: The mean follow-up was 9.3 years. Complete resolution of numbness was reported by 93.8% of patients, persistent numbness by 3.8%, and recurrent numbness by 2.5%. The mean BCTQ symptom score was 1.1 (sd 0.3; 1.0 to 2.55) and the mean Boston function score was 1.15 (sd 0.46; 1.0 to 3.5). 72.5% of patients were asymptomatic and had no functional impairment. Men had poorer outcomes than women and patients < 55 years had poorer outcomes than patients ≥ 55 years. All patients who had undergone endoscopic CTR reported complete resolution of numbness compared with 89.1% of those who had undergone open release (p = 0.047). There was no significant difference in outcome between dominant and non-dominant hands. Patient satisfaction rates were good. There were no adverse events. CONCLUSION: CTR has a favourable outcome and good rates of satisfaction, even in patients with bilateral severe CTS at a mean of nine years after surgery. Endoscopic CTR has a higher rate of numbness resolution than open surgery. There were no significant differences in outcome between the dominant and non-dominant hand. Cite this article: Bone Joint J 2017;99-B:1348-53.

Biochemical characterization and substrate specificity of rat prostate kallikrein (S3): comparison with tissue kallikrein, tonin and T-kininogenase.

A tissue kallikrein-like enzyme encoded by S3 mRNA was purified to homogeneity from rat prostate gland. The apparent molecular mass of the prostate enzyme is 32 kDa as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The intact 32 kDa enzyme is split into two bands of lower molecular mass, 18 and 14 kDa, under reducing conditions on SDS-PAGE. NH2-terminal amino acid sequence analyses of the intact enzyme and heavy and light chains revealed the identity to the translated sequence of a prostate kallikrein cDNA (S3). Isoelectric focusing indicated that the prostate enzyme is a basic protein with pI of 7.30-7.45. Specific activities of the prostate kallikrein toward angiotensin I, angiotensinogen and rat low M(r) kininogen as well as tripeptide chromogenic substrates were compared with those of tissue kallikrein, tonin and T-kininogenase. The kinin-releasing activity is inhibited by leupeptin, antipain, benzamidine and soybean trypsin inhibitor. A sensitive and specific radioimmunoassay for the rat prostate kallikrein shows that the immunoreactive kallikrein levels in prostate and submandibular gland were 23.78 +/- 2.62 micrograms/mg protein (n = 5) and 12.29 +/- 2.25 micrograms/mg protein (n = 5), respectively. The results indicate that the prostate kallikrein S3 is expressed at high levels in both prostate and submandibular glands.

Extensive disinhibitory region beyond the classical receptive field of cat retinal ganglion cells.

Forty-three single fibres were recorded from cat optic tract. They were tested with flashing lines of different lengths and/or spots of different dimensions. The area of centre excitation and of surround inhibition were represented in the length (or dimension)-response functions by the steep rising and falling phases, respectively. For most of the cells, a secondary gentle rise was seen when the stimulus extended beyond the inhibitory surround, indicating an extensive disinhibitory region (DIR) outside the classical receptive field (RF). Disinhibition appeared and developed concurrently with surround inhibition at stimulus intensities between 3 and 30 cd/m2, being represented in the phasic or the tonic component of responses depending on the cell type recorded.

[Comparison between responses of monkey prefrontal neurons to signal and to indifferent stimuli].

Unit activities of the principal sulcus area were recorded in three monkeys (Macaca mullata). Two of them were trained to perform visual discrimination task, and the other had not received any training. The sequence of the task is as follows: (1) a cue of presentation of red (in R Model) or blue (in B Model) light (1.3s); (2) a delay period (2.1s); (3) a reaction period of presentation of white light (4.88s). The monkey should draw a bar after the onset of the white light of R Model to avoid a electric shock, and should not draw the bar after the onset of the white light of B Model in which the monkeys would not receive the electric shock. Of 127 prefrontal units recorded from the two trained monkeys when they were performing the task, 80 units (63%) were related to the events of the task. Ninety six units were recorded for the test of responses to click and flash in the intertrial interval, and 23 units (24%) responded to click and/or flash. Fifteen out of 23 units were event-related. Twelve out of 103 units responded to the red, blue and white flash in the intertrial interval. A hundred units were recorded from the untrained monkey a only 4 units showed nonspecific responses to the indifferent stimuli. The results showed that after training much more prefrontal neurons involved in processing of the information of signal stimuli than those in response to the indifferent stimuli. In other words, the prefrontal neurons possess plasticity and change their activities during the training of visual discrimination task.

In vivo catabolism of human kallikrein-binding protein and its complex with tissue kallikrein.

We recently identified and purified a novel human kallikrein-binding protein (HKBP) from human plasma. The HKBP forms a 92 kd sodium dodecyl sulfate-stable and heat-stable complex with tissue kallikrein. This study was undertaken to characterize the plasma clearance and tissue distribution of exogenously administered HKBP and its complex with tissue kallikrein. Human tissue kallikrein was first incubated with purified HKBP, and the high-molecular-weight complex was separated from unbound proteins on a high-pressure liquid chromatography gel filtration column. Tissue kallikrein, kallikrein-binding protein, and their complex were labeled with iodine-125 and then injected intravenously into Sprague-Dawley rats. The disappearance rates of trichloracetic acid-precipitable radioactivity from the circulation were determined. The clearance profile of HKBP shows a nonlinear pattern with an apparent half-life of 65 minutes (n = 4). The plasma clearance of HKBP complexed with kallikrein shows a similar profile but a shorter half-life of 33 minutes (n = 3). HKBP and its complex with kallikrein were mainly taken up by the liver but to a lesser degree by the kidney, lung, and other tissues. Labeled human kallikrein has an apparent half-life of 8 minutes (n = 4), and its clearance consists of a fast and a slow component. The data indicate that kallikrein-HKBP complex is cleared from the circulation two times faster than that of the binding protein alone and that it persists in the circulation four times longer than kallikrein alone. The results support the notion that more than one pathway exists for the metabolism of tissue kallikrein and that HKBP plays a role in modulating tissue kallikrein's bioavailability.