Cerebral Blood Flow Alterations in Sepsis-Associated Encephalopathy: A Prospective Observational Study.

BACKGROUND: The timely recognition of sepsis-associated encephalopathy (SAE) remains a challenge. This study aimed to observe the CBF changes via TCD during sepsis and explore their possible predictive value in SAE. METHODS: In this prospective observational study, septic patients were enrolled and classified according to the diagnosis of SAE into two groups: SAE group and non-SAE group. Then SAE patients were further divided into subgroup A (the type with agitation) and subgroup B (the type with depressed consciousness) based on their clinical manifestations. The clinical profiles and TCD parameters within 24 hours of onset were compared between groups and subgroups. RESULTS: Exactly 198 septic patients were enrolled including 65 patients in SAE group (36 male/29 female with a median age of 70) and 133 patients in non-SAE group (75 male/58 female with a median age of 67). Significant elevated peak-systolic velocity (VS; 107 [69-138] cm/s vs 85 [69-101] cm/s, P = .002) of the left middle cerebral artery (MCA) and pulsatility index (PI; left: 0.99 [0.81-1.34] vs 0.89 [0.76-1.00], P < .001; right: 0.99 [0.77-1.21] vs 0.88 [0.78-1.03], P = .007) of bilateral MCAs were found in SAE group compared with non-SAE group. In subgroup analysis, subgroup A (the type with agitation) showed significantly increased VS/VM/VD and lower PI/RI of bilateral MCAs compared with subgroup B (the type with depressed consciousness). The cerebral blood flow volume of subgroup A were obviously higher than subgroup B [858.7 (729.1,876.9) mL/s vs 380.9 (373.3,447.4) mL/s, P < .001]. CONCLUSIONS: This study confirmed the abnormal CBF among SAE and found different types of CBF alterations were related to different clinical features. VS and PI might help clinicians to early identify different types of SAE.

Contrast-Enhanced Ultrasonography Value for Early Prediction of Delayed Graft Function in Renal Transplantation Patients.

OBJECTIVES: Delayed graft function (DGF) is a common early complication after kidney transplantation. The aim of the present study was to evaluate the value of contrast-enhanced ultrasonography (CEUS) in the early prediction of DGF after kidney transplantation. METHODS: A total of 89 renal transplant recipients were retrospectively enrolled and divided into DGF group or normal graft function (NGF) group according to the allograft function. Conventional Doppler ultrasound and CEUS examination data on the first postoperative day were collected and analyzed. RESULTS: The resistive indices of segmental and interlobar artery in the DGF group were significantly higher than those in the NGF group (0.71 ± 0.17 versus 0.63 ± 0.08, P = .006; 0.70 ± 0.16 versus 0.62 ± 0.08, P = .004, respectively). The patients experiencing DGF had significantly lower PI-c (14.7 dB ± 6.1 dB versus 18.5 dB ± 3.3 dB, P = .001) and smaller AUC-c (779.8 ± 375.8 dB·seconds versus 991.0 ± 211.7 dB·seconds, P = .003), as well as significantly lower PI-m (12.6 dB ± 5.9 dB versus 15.9 dB ± 3.9 dB, P = .006), shorter MTT-m (30.7 ± 9.4 seconds versus 36.3 ± 7.1 seconds, P = .01), and smaller AUC-m (P = .007). Multivariate analysis demonstrated that PI-c, AUC-c, and MTT-m were independent risk factors for DGF. The area under the receiver operating characteristic curve values of the combined predicted value (PI-c + MTT-m, PI-c + AUC-c + MTT-m) of DGF incidence were bigger than that of PI-c, AUC-c, or MTT-m. CONCLUSIONS: CEUS parameters of the cortex and medulla have a good value for an early prediction of DGF after renal transplantation.

Comparative study of high flow nasal catheter device and noninvasive positive pressure ventilation for sequential treatment in sepsis patients after weaning from mechanical ventilation in intensive care unit.

BACKGROUND: The hypoxemia condition after mechanical ventilation (MV) weaning is not rare among sepsis patients, so we compared the efficacy in two different intervention groups: high-flow nasal cannula device group and non-invasive positive pressure ventilation (NPPV) group. METHODS: This is a retrospective cohort study. Participants were patients with sepsis receiving high-flow nasal catheter (HFNC) device or NPPV within 24 hours after weaning from MV. The primary outcome was tracheal re-intubation within 72 hours after extubation. Secondary outcomes included: oxygenation index, complication rate, patient comfort evaluation, HFNC/NPPV treatment time, ICU length of stay (LOS), ICU mortality, and in-hospital 28-day mortality. RESULTS: A total of 283 patients were included in the study with 167 in the HFNC group and 116 in the NPPV group. The re-intubation rates after extubation in both groups were respectively 4.2% and 5.2% without significant difference. Patients in the HFNC group experienced lower incidence of delirium, reflux aspiration, facial pressure ulcer and other complications, and higher score of patients comfort than that in the NPPV group. There was no significant difference in ICU LOS, ICU mortality and in-hospital 28-day mortality between the two groups. CONCLUSIONS: HFNC and NPPV have similar efficacy in the sequential treatment of sepsis patients after weaning from MV. Compared with NPPV, those extubated to HFNC had lower rate of complications such as reflux aspiration and facial pressure ulcers. The patients extubation to HFNC is more comfortable (and associated with less delirium) than to NPPV.

miR-124-3p targeting of TGF-ß1 inhibits the proliferation of hypertrophic scar fibroblasts.

BACKGROUND: microRNAs are involved in a variety of physiological and pathophysiological processes, but their role in the pathogenesis of hypertrophic scars (HS) is not fully understood. Transforming growth factor ß1 (TGF-ß1) plays an important role in the genesis and development of HS. OBJECTIVES: In this study, we hypothesized that a post-translational miRNA mechanism regulates the expression of TGF-ß1 in HS fibroblasts (HSFBs) and participates in the development of HS. MATERIAL AND METHODS: Predictions from EBCORI, PicTar and miRBase databases showed that miR-124-3p can target and regulate the expression of TGF-ß1. We collected HS tissue and corresponding normal tissue from 25 patients with HS who had been operated on for the first time. RESULTS: The expression level of miR-124-3p in HS tissue was significantly lower than in normal tissue, while the expression level of TGF-ß1 mRNA was significantly higher than in normal tissue (p < 0.05), showing a negative correlation between them. Results from a luciferase reporter assay showed that miR-124-3p targets the 3'-UTR of TGF-ß1 and inhibits its expression. After miR-124-3p mimics were transfected into HSFBs, the expression of TGF-ß1, α-smooth muscle actin (α-SMA), collagen I, survivin, and Bcl-2 were reduced and the expression of Bax was increased, with significant decreases in DNA synthesis, proliferation and survival. However, after a miR-124-3p inhibitor was transfected into HSFBs, these effects were reversed as the expression of TGF-ß1, α-SMA, collagen I, survivin, and Bcl-2 increased, expression of Bax decreased, and DNA synthesis, proliferation and survival cells increased significantly. CONCLUSIONS: miR-124-3p can inhibit the proliferation of HSFBs by targeting TGF-ß1, and miR-124-3p may thus be a potential therapeutic target in HS.

Ulinastatin ameliorates LPS­induced pulmonary inflammation and injury by blocking the MAPK/NF­κB signaling pathways in rats.

Ulinastatin, a urinary trypsin inhibitor (UTI) is commonly used to treat patients with acute inflammatory disease. However, the underlying mechanisms of its anti­inflammatory effect in acute lung injury (ALI) are not fully understood. The present study aimed to investigate the protective effect of UTI and explore its potential mechanisms by using a rat model of lipopolysaccharide (LPS)­induced ALI. Rats were treated with 5 mg/kg LPS by intratracheal instillation. The histological changes in LPS­induced ALI was evaluated using hematoxylin and eosin staining and the myeloperoxidase (MPO) activity was determined using ELISA. The wet/dry ratio (W/D ratio) of the lungs was used to assess the severity of pulmonary edema and Evans blue dye was used to evaluate the severity of lung vascular leakage. The results demonstrated that LPS administration induced histological changes and significantly increased the lung W/D ratio, MPO activity and Evans blue dye extravasation compared with the control group. However, treatment with UTI attenuated LPS­induced ALI in rats by modifying histological changes and reducing the lung W/D ratio, MPO activity and Evans blue dye extravasation. In addition, LPS induced the secretion of numerous pro­inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor­α, interleukin (IL)­6, IL­1ß and interferon­Î³; however, these cytokines were strongly reduced following treatment with UTI. In addition, UTI was able to reduce cellular counts in BALF, including neutrophils and leukocytes. Western blotting demonstrated that UTI significantly blocked the LPS­stimulated MAPK and NF­κB signaling pathways. The results of the present study indicated that UTI could exert an anti­inflammatory effect on LPS­induced ALI by inhibiting the MAPK and NF­κB signaling pathways, which suggested that UTI may be considered as an effective drug in the treatment of ALI.

[Relationship between blood lactate level and the prognosis of patients with diabetic sepsis].

OBJECTIVE: To evaluate the prognostic value of blood lactate (Lac) level in sepsis patients with or without diabetes. METHODS: 106 patients admitted to intensive care unit (ICU) of Zhongshan Hospital Affiliated to Fudan University from April 2015 to November 2016 were enrolled. The patients with age > 18 years and the length of hospital stay > 24 hours were included. Records including blood Lac, serum creatinine (SCr), white blood cell count (WBC), platelet count (PLT), sequential organ failure assessment (SOFA) on the first day of admission; minimum oxygen index (PaO2/FiO2) in 3 days after admission; mechanical ventilation, whether there was a history of diabetes, usage of biguanides, etiology control treatment, usage of continuous renal replacement therapy (CRRT) were collected. According to the level of blood Lac patients were divided into high Lac group (Lac > 2 mmol/L) and low Lac group (Lac ≤ 2 mmol/L); based on their diabetic history, sepsis patients were divided into the diabetes group and non-diabetes group. The survival curve of each group was analyzed by Kaplan-Meier regression analysis, and the factors influencing the prognosis were analyzed by multivariate Cox regression analysis. RESULTS: There were 76 males and 30 females sepsis patients, with an average age of (68.1±14.7) years old. In the 51 patients of low Lac group, there were 7 patients who suffered from diabetes. While in the 55 patients of high Lac group, there were 12 patients who suffered from diabetes. Compared with low Lac group, high Lac group had a higher age, higher SOFA score, and a lower proportion of patients who had the treatment of etiology control (all P < 0.05). There was no significant difference of blood Lac in sepsis patients with diabetes and those without diabetes (mmol/L: 3.03±2.73 vs. 2.81±2.40, P > 0.05). Kaplan-Meier survival curve analysis showed that the 90-day survival rate in the high Lac group was significantly lower than that in the low Lac group (56.36% vs. 90.20%, χ 2 = 0.697, P = 0.008). The high Lac group without diabetes had lower survival rate, and the 90-day survival rate was significantly lower than that of the low Lac group without diabetes (58.14% vs. 90.90%, χ 2 = 7.152, P = 0.007); there was no significant difference in 90-day survival rate between the high Lac group and the low Lac group with diabetes (50.00% vs. 85.71%, χ 2 = 0.012, P = 0.914). Multivariate Cox regression analysis showed that blood Lac was an independent risk factor for the prognosis of sepsis patients [odds ratio (OR) = 3.863, 95% confidence interval (95%CI) = 1.237-12.060, P = 0.020]. After stratification according to their diabetic history, the blood Lac was an independent risk factor for the prognosis of sepsis patients without diabetes (OR = 4.816, 95%CI = 1.407-15.824, P = 0.010), but the blood Lac had no effect on the prognosis of sepsis patients with diabetes (OR = 0.000, 95%CI = 0.000-1.103, P = 0.270). CONCLUSIONS: The predictive value of blood Lac on sepsis patients with or without diabetes was different. The blood Lac was related with the prognosis of sepsis patients without diabetes, while further study should be conducted for the prognostic value of blood Lac in sepsis patients with diabetes, and it's possible to increase the cut-off-point of Lac level in these patients.

Role of Magnetic Resonance Imaging in Detection of Pathologic Complete Remission in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: A Meta-analysis.

Pathologic complete remission after neoadjuvant chemotherapy has a role in guiding the management of breast cancer. The present meta-analysis examined the accuracy of contrast-enhanced magnetic resonance imaging (CE-MRI) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting the response to neoadjuvant chemotherapy and compared CE-MRI with ultrasonography, mammography, and positron emission tomography/computed tomography (PET/CT). Medical subject heading terms and related keywords were searched to generate a compilation of eligible studies. The pooled sensitivity, specificity, diagnostic odds ratio, area under summary receiver operating characteristic curve (AUC), and Youden index (Q* index) were used to estimate the diagnostic efficacy of CE-MRI, DW-MRI, ultrasonography, mammography, and PET/CT. A total of 54 studies of CE-MRI and 8 studies of DW-MRI were included. The overall AUC and the Q* index values for CE-MRI and DW-MRI were 0.88 and 0.94 and 0.80 and 0.85, respectively. According to the summary receiver operating characteristic curves, CE-MRI resulted in a higher AUC value and Q* index compared with ultrasonography and mammography but had values similar to those of DW-MRI and PET/CT. CE-MRI accurately assessed pathologic complete remission in specificity, and PET/CT and DW-MRI accurately assessed pathologic complete remission in sensitivity. The present meta-analysis indicates that CE-MRI has high specificity and DW-MRI has high sensitivity in predicting pathologic complete remission after neoadjuvant chemotherapy. CE-MRI is more accurate than ultrasonography or mammography. Additionally, PET/CT is valuable for predicting pathologic complete remission. CE-MRI, combined with PET/CT or DW-MRI, might allow for a more precise assessment of pathologic complete remission.