Comparing acute normovolumic hemodilution with autologous platelet-rich plasma for blood preservation during aortic surgery : study protocol for a randomized controlled clinical trial.

BACKGROUND: Both acute normovolumic hemodilution (ANH) and autologous platelet-rich plasma (aPRP) have been demonstrated blood-protective effects in cardiac aortic surgery; however, the efficacies of the two methods have not been compared. This study aims to compare the effects of aPRP and ANH prior to aortic surgery on postoperative bleed and other outcomes. METHODS AND ANALYSIS: This is a prospective, single-center, double-blind controlled clinical trial including 160 patients randomized 1:1 to receive aPRP (test group) or autologous whole blood (ANH, control group). The primary objective is to compare the drainage volumes in the two groups at 24, 48, and 72 h postoperatively. Secondary outcomes include input of allogeneic blood and blood products and durations of aortic block, extracorporeal circulation, deep hypothermic arrest of circulation, tracheal extubation, hospital stay, requirement for secondary surgical hemostasis, and application of intra-aortic balloon pump or extracorporeal membrane oxygenation in the two groups. In addition, heart rate, systolic blood pressure, diastolic blood pressure, central venous pressure, and thromboelastography recorded before blood reservation (T1), after blood reservation (T2), before blood transfusion (T3), and after the blood is returned (T4) to the transfusion will be compared between the two groups of patients. DISCUSSION: This study will demonstrate if the use of aPRP could reduce the risk of bleeding after aortic surgery compared with ANH. The results are expected to have practical clinical applications in terms of more effective blood protection and shorter hospital stay. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) with the ID ChiCTR 1900023351.Registered on May 23, 2019. TRIAL STATUS: Recruiting start date: July 1, 2019; expected recruiting end date: July 1, 2024 Version number and date: Version 2 of 05-04-2019.

Comparison of amiodarone and esmolol for prevention of reperfusion ventricular fibrillation in individuals undergoing heart valve or aortic surgery: a study protocol for a randomized controlled clinical trial.

BACKGROUND: Amiodarone and esmolol can help to prevent and treat post-cardiac surgery reperfusion ventricular fibrillation. However, the relative efficacies of these two drugs remain unknown. The aim of the current trial is to compare the performances of amiodarone and esmolol for preventing reperfusion ventricular fibrillation following open heart surgery. METHODS/DESIGN: This is a single-center, prospective, double-blind, controlled clinical trial. A total of 260 patients undergoing heart valve or aortic surgery will be assigned randomly to treatment with prophylactic esmolol (intervention group) or amiodarone (control group). The main outcome is the incidence of reperfusion ventricular fibrillation following aortic opening during extracorporeal circulation. The secondary outcomes are the rate of automatic cardiac resuscitation, energy and frequency of electrical defibrillation, number of electrical defibrillations, and pacemaker use in the two groups of patients. Information on the patients' general condition and the durations of anesthesia, extracorporeal circulation, aortic occlusion, and operation time will be recorded. We will also compare the heart rate, mean arterial pressure, and central venous pressure between the two groups of patients at induction of anesthesia (T1), start of surgery (T2), start of extracorporeal circulation (T3), aortic block (T4), aortic opening (T5), after opening for 10 (T6), 20 (T7), and 30 min (T8), at cessation of extracorporeal circulation (T9), and at the end of surgery (T10) and compare blood gas analysis results at T1, T5, T9, and T10. DISCUSSION: This study will determine if prophylactic esmolol is more effective than amiodarone for reducing the incidence of reperfusion ventricular fibrillation in patients undergoing heart valve or aortic surgery. TRIAL REGISTRATION: China Clinical Trials Registry ChiCTR1900026429. Registered on 2019.10.9.

[Regulation of colony-stimulating factor 1 receptor inhibitor pexidartinib on the senescence of mouse bone marrow-derived macrophages stimulated by lipopolysaccharide].

Objective: To investigate the effects of colony-stimulating factor 1 receptor (CSF-1R) inhibitor pexidartinib (PLX3397) on the senescence of bone marrow-derived macrophages (BMDM) stimulated by lipopolysaccharide (LPS). Methods: BMDM were isolated and cultured from femurs and tibiae of 10 male C57BL/6 mice aged 6-8 weeks (obtained from Laboratory Animal Center of Guizhou Medical University). They were divided into blank control group, LPS group (treated with 1 µg/ml LPS for 24 h) as well as low, medium and high concentration PLX3397 pretreatment groups (treated with 100, 500 and 1 000 nmol/L PLX3397 for 4 h respectively followed by 1 µg/ml LPS for 24 h). The corresponding markers of macrophages were detected by flow cytometry. Cell viability was detected by cell counting kit-8 and cellular senescence was detected by senescence-associated-ß-galactosidase (SA-ß-gal) staining. Meanwhile, protein expressions of cycle-dependent kinase inhibitor p16, p21 and CSF-1R were detected by Western blotting, and the expressions of p16 and p21 were detected by intracellular immunofluorescence. Real-time fluorescence quantitative PCR (RT-qPCR) was used to investigate the mRNA levels of senescence-associated secretory phenotype (SASP) genes including interleukin (IL), IL-1ß, chemokine-1/10 (CXCL-1/10), matrix metalloproteinase-8 (MMP-8), and transforming growth factor-ß (TGF-ß). Results: The rate of SA-ß-gal positive staining in medium and high concentration PLX3397 pretreatment groups [(39.33±4.93)% and (36.33±3.06)% respectively] were significantly downregulated compared with LPS group [(52.00±3.00)%] (P=0.020, P=0.005). The expression of CSF-1R protein in low, medium and high concentration PLX3397 pretreatment groups were (0.74±0.18, 0.61±0.07, 0.54±0.06), all of which were significantly lower than that in LPS group (1.16±0.08) (P=0.013, P=0.002, P<0.001). The expression levels of CSF-1R mRNA in low, medium and high concentration PLX3397 pretreatment groups (1.04±0.06, 0.90±0.05, 1.18±0.08) showed similar trend (2.90±0.25) (P<0.001). The average fluorescence intensity of p16 in all PLX3397 pretreatment groups were 49.76±3.65, 48.21±1.72, 47.99±1.26 respectively, which were significantly lower than that in LPS group (66.88±5.85) (P=0.001, P<0.001, P<0.001). The average fluorescence intensity of p21 in medium and high concentration PLX3397 pretreatment groups were (34.43±3.62, 30.13±0.86), significantly lower than that in LPS group (46.82±5.33) (P=0.043, P=0.007). The expression of p16 protein in low, medium and high concentration PLX3397 pretreatment groups (0.56±0.04, 0.55±0.04, 0.35±0.19) were significantly lower than that in LPS group (0.98±0.10) (P=0.003, P=0.002, P<0.001), as well the expression of p21 protein (0.69±0.20, 0.42±0.08, 0.26±0.14) (P=0.032, P=0.002, P<0.001). According to the results of RT-qPCR, the expressions of IL-6, IL-1ß, CXCL-1, CXCL-10 and MMP-8 in PLX3397 pretreatment groups were significantly lower than those in LPS group (P<0.001), while the expression of TGF-ß increased (P<0.001). Conclusions: LPS could induce the cell senescence, increase the secretion of SASP and aggravate local inflammation by activating the CSF-1R on the cell surface of bone marrow-derived macrophages. CSF-1R inhibitor PLX3397 might attenuate CSF-1R activation associated with LPS and inhibit the senescence of bone marrow-derived macrophages induced by LPS.

d-Alanine: Distribution, origin, physiological relevance, and implications in disease.

d-Alanine (d-Ala) is an unusual endogenous amino acid present in invertebrates and vertebrates. Compared to its l-isomer, the characterization of d-Ala is challenging because of the need for chiral resolution and the low amounts of the d-enantiomer present. With recent improvements in measurement capabilities, research on d-Ala, along with other d-amino acids, has been growing, especially as the functional significance of d-Ala in the mammalian nervous and endocrine systems is becoming known. Here we provide an overview of the distribution, origin, function, and disease implications of d-Ala.

Effects of ultrasound-guided stellate-ganglion block on sleep and regional cerebral oxygen saturation in patients undergoing breast cancer surgery: a randomized, controlled, double-blinded trial.

Numerous factors could contribute to sleep disturbances in women with breast cancer. We hypothesized that stellate ganglion block (SGB) during surgery would preserve sleep after surgery and increase intraoperative regional cerebral oxygen saturation (rSO2) on the blocked side in patients undergoing breast cancer surgery. A randomized, double-blinded, controlled trial was conducted at the First Hospital of China Medical University from January 2016 to September 2016. Ninety-six patients who underwent radical breast cancer surgery requiring general anaesthesia were randomly assigned to one of two study groups: a control group that received a saline SGB and a block group that received a 0.25% ropivacaine hydrochloride SGB. The primary outcome measure was the postoperative sleep profile, which was assessed using the bispectral index on the first postoperative night. The secondary outcome measure was the intraoperative rSO2, monitored was throughout surgery using near-infrared spectroscopy. A total of 91 female patients (mean age: 45 years; range 24-51 years) were included in the study. The duration of sleep was significantly increased by 66.3 min in the ropivacaine-SGB group compared with the saline-SGB group. No differences in rSO2 were observed on either the left or right side of the patients in either group 50 min after anaesthesia induction. We conclude that ropivacaine-SGB combined with general anaesthesia might increase the first postoperative sleep duration without influencing the intraoperative rSO2 in female patients undergoing elective breast cancer surgery. Clinical trials.gov identifier NCT02651519.

Supraclavicular block versus interscalene brachial plexus block for shoulder surgery: A meta-analysis of clinical control trials.

BACKGROUND: The ultrasound-guided interscalene block (ISB) has been considered a standard technique in managing pain after shoulder surgery. However, this method was associated with the incidence of hemi-diaphragmatic paresis. In contrast to ISB, supraclavicular block (SCB) was suggested to provide effective anaesthesia for shoulder surgery with a low rate of side-effects. Thus, we performed a meta-analysis of randomised controlled trials (RCTs) to compare SCB with ISB for evaluating the efficacy and safety. METHOD: The literature was searched from PubMed, Wiley Online Library, EMBASE, and the Cochrane Library by two reviewers up to April 2017. All available RCTs written in English that met the criteria were included. Two authors pulled data from relevant articles and assessed the quality with the Cochrane Handbook. Review Manager 5.3 software was used to analyse the data. RESULTS: Five RCTs and one prospective clinical study met the eligibility criteria and were included in the meta-analysis. We considered that there were no statistically significant differences between supraclavicular and interscalene groups in procedural time (P = 0.81), rescue analgesia (P = 0.53), and dyspnoea (P = 0.6). The incidence of hoarseness and Horner syndrome was statistically lower in the SCB group than in the ISB group (P = 0.0002 and P < 0.00001, respectively). CONCLUSION: The meta-analysis showed that ultrasound-guided SCB could become a feasible alternative technique to the ISB in shoulder surgery.

Seroepidemiology of Toxoplasma gondii infection in patients with liver disease in eastern China.

The role of the protozoan parasite Toxoplasma gondii in the pathogenesis of liver disease has recently gained much interest. The aim of this study was to determine the prevalence and risk factors associated with T. gondii infection in patients with liver disease from three cities in Shandong and Henan provinces, China. A case-control study was conducted from December 2014 to November 2015 and included 1142 patients with liver disease and 1142 healthy controls. Serum samples were collected from all individuals and were examined with enzyme-linked immunosorbent assay for the presence of anti-T. gondii IgG and IgM antibodies. Information on the demographics, clinical, and lifestyle characteristics of the participants was collected from the medical records and by the use of a questionnaire. The prevalence of anti-T. gondii IgG was 19·7% in patients with liver disease compared with 12·17% in the controls. Only 13 patients had anti-T. gondii IgM antibodies compared with 12 control individuals (1·14% vs. 1·05%, respectively). The highest seroprevalence was detected in patients with liver cancer (22·13%), followed by hepatitis patients (20·86%), liver cirrhosis patients (20·42%), and steatosis patients (20%). Multivariate logistic regression analysis indicated that consumption of raw meat (odds ratio (OR) = 1·32; 95% confidence interval (CI) 1·01-1·71; P = 0·03) and source of drinking water from wells (OR = 1·56; 95% CI 1·08-2·27; P = 0·01) were independent risk factors for T. gondii infection in liver disease patients. These findings indicate that T. gondii infection is more likely to be present in patients with liver disease. Therefore, efforts should be directed toward health education of populations at high risk of T. gondii infection and measures should be taken to protect vulnerable patients with liver disease.

[Activation of transcription factor NF-κB in a rat model of cardiac fibrosis induced by ß-adrenoceptor stimulation].

OBJECTIVE: To establish a model of cardiac fibrosis induced by isoproterenol (ISO), the non-selective ß adrenoceptor agonist, injected subcutaneously for 7 days in rats, and to observe changes of transcription factor NF-κB in the model. METHODS: Male SD rats weighing 280-320 g were injected with ISO (0.25 mg/kg/d) subcutaneously for 7 days to induce cardiac fibrosis. The collagen volume fraction was determined by quantitative morphometry of picrosirius red stained left ventricular sections. Collagen types I/III and IL-6 mRNA expressions were analyzed by real time PCR. The pathological changes of the heart were investigated by Hematoxylin and Eosin staining. NF-κB was localized by immunohistochemistry (IHC) and phosphorylated NF-κB levels were assessed by Western blot analysis. RESULTS: Compared with the controls, ISO significantly elevated the sirius red stained area and collagen volume fraction (12.01±1.644 vs. 0.95±0.067, P<0.001). Similarly, ISO increased the mRNA expressions of collagen Iand collagen III of the heart compared with the controls (10.51±0.47 vs. 0.98±0.02,P<0.001 for collagen I; 9.58±1.33 vs. 1.02±0.02, P<0.001 for collagen III). The number of nuclei was increased and nuclear accumulation was presented in myocardial tissue induced by ISO. The mRNA expression of IL-6 increased in ISO group (1.64±0.18 vs. 1.04±0.07, P<0.01). ISO induced NF-κB nuclear translocation, accompanied by an increase in phosphorylation of NF-κB (10.83±2.05 vs. 1.05±0.27, P<0.001). CONCLUSION: We conclude that the model of cardiac fibrosis can be successfully induced by ISO injected subcutaneously for 7 days in rats and the activation of nuclear factor NF-κB increased by ß-adrenoceptor stimulation.

Protective effects of propofol on endotoxemia-induced acute kidney injury in rats.

1. Animal studies suggest that propofol protects against endotoxaemia-induced lung and kidney injury. Upregulation of aquaporin expression in lung tissue mediates these effects, but the mechanism of action in the kidney is unclear. The present study examined the protective effects of propofol on endotoxaemia-induced acute kidney injury in rats. 2. A rat model of endotoxaemia was established using lipopolysaccharide (LPS). We determined the effects of 10% propofol administration 1 h before, during and 1 h after LPS-induced endotoxaemia on expression of aquaporin (AQP)-2, tumour necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, caspase 3, Bcl-2 and Bax using reverse transcription-polymerase chain reaction, western blotting and immunocytochemistry. Renal morphology, superstructure, apoptosis and function were also assessed. 3. Normal renal tubular structure was seen in the propofol pretreated group, but LPS treatment resulted in changes to renal tissue morphology. Propofol treatment improved renal function in LPS-treated rats. Pretreatment with propofol 1 h before LPS normalized urine and serum osmolality, serum creatinine and blood urea nitrogen to control levels. Lipopolysaccharide downregulated expression of AQP-2 and downregulated the expression of ICAM-1 and TNF-α. These effects were reversed by propofol treatment. Lipopolysaccharide reduced the Bcl2 : Bax ratio and induced renal cell apoptosis and these effects were reduced by propofol treatment. Overall, propofol pretreatment had greater effects than concurrent treatment or propofol administration after LPS induction of endotoxaemia. 4. In conclusion, propofol pretreatment protected renal function in a rat model of endotoxaemia. Further studies are necessary to confirm this effect in other experimental models and in humans.

Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats.

Postoperative cognitive dysfunction (POCD) is characterized by the progressive deterioration of intellectual/cognitive function following surgery. It has been suggested that the senile brain, which characteristically expresses higher levels of central proinflammatory cytokines, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, is more susceptible to additional insult following surgery. The authors of this study investigated the expression of central cytokines IL-1ß, IL-6 and TNF-α and hippocampal glial cell activation in aged and adult rats following partial hepatectomy. Cognitive function was assessed in a reversal-learning version of the Morris water maze (MWM) before and after surgery. Hippocampal pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α and glial cell activation markers glial fibrillary acidic protein (GFAP) and S100ß were measured at each time point; CD200 and CD200R were also measured to explore potential mechanisms of glial cell activation. Surgical trauma resulted in impairments in distance and latency only on postoperative day 1 (p<0.001, respectively) in adult rats. Aged rats exhibited impairments on day 1 (p<0.001) that persisted until postoperative day 3 (p=0.002 and p=0.001, respectively). All significant impairments paralleled upregulated cytokine IL-1ß and IL-6 expression. Immunohistochemistry assay further showed more hippocampal glial cell activation in aged rats compared to that in adults. Overall, these findings suggest that surgical trauma, rather than anesthesia, resulted in cognitive function impairment potentiated by aging. Hippocampal pro-inflammatory cytokines and glial cell activation might mediate trauma-induced POCD.

[Clinical study of the sentinel lymph node of patients with laryngeal and hypopharyngeal carcinomas].

OBJECTIVE: To investigate the methods of detecting the sentinel lymph node of laryngeal and hypopharyngeal carcinomas and its predictive value in the cervical metastasis of the carcinoma. METHODS: In 29 patients who suffered from laryngeal or hypopharyngeal carcinoma with NO neck, the patent blue was injected into the surrounding tissue of the tumor during the operation to identify the sentinel lymph nodes. The sentinel lymph nodes were dyed blue. The frozen histopathology was done during the operation, the lymph nodes at the ipsilateral side of the neck were dissected completely, and the routine histopathology was done as the gold standard to study the predictive value of the sentinel lymph node in the metastasis of the cervical node. RESULTS: Of 29 patients, 28 patients' sentinel lymph nodes were detected successfully during operation. There was an average of 2.5 lymph nodes per side per patient. Most of the sentinel lymph nodes were in the level II and level III regions of the ipsilateral side of the neck, and there were bilateral sentinel nodes in patients suffered from superglottic carcinoma. Three patients' sentinel lymph nodes were found to be positive in the frozen inspection, and the routine histopathology confirmed the result. The micrometastasis rate was 10.7% (3/28). There were no metastatic lymph nodes found in patients who were negative for the sentinel lymph nodes during the operative frozen histopathology. The predicted value of the sentinel lymph nodes to the cervical lymph node metastasis was 100 per cent. CONCLUSION: There is a very important predicted value of sentinel lymph nodes in the cervical metastasis of patients suffered from laryngeal and hypopharyngeal carcinomas. It could reduce the neck dissection in patients with laryngeal and hypopharyngeal carcinomas.

[Factors affecting prognosis of papillary thyroid carcinoma with bilateral cervical lymph node metastases].

One hundred thirty nine cases of papillary thyroid carcinoma with bilateral lymph node metastases were reviewed. They were surgically treated at the Cancer Hospital of Shanghai Medical University in the years from 1956 through 1990. There were 73 men and 66 women with a median age of 35 (range 11-70) years. The median follow-up period was 11 years. Kaplan-Meier survival curves were calculated for the population. The overall survival rate was 94.7% at 5 years, 85.9% at 10 years, and 82.3% at 15 years. In univariate analysis, factors influencing prognosis are age at diagnosis, tumor size, extrathyroidal invasion, residual tumor and thoroughness of excision. When Cox proportional risk model was applied to analyze the survival data, factors of survival significance are the age at diagnosis and thoroughness of excision.

The infrahyoid myocutaneous flap for reconstruction after resection of head and neck cancer.

From May 1979 to August 1984, 112 infrahyoid myocutaneous flaps (IHMCFs) were used for reconstruction of the tongue after resection of lingual carcinoma (67 flaps in 63 consecutive cases) and for repair of defects after resection of carcinomas of buccal mucosa (23 cases), floor of mouth (8 cases), parotid gland (7 cases), and other malignancies (7 cases). Ten IHMCFs were extended to Ludwig's angle for repairing the open defect of the cheek or combined defect in the buccal mucosa and hard palate. The donor sites of 76 IHMCFs could be sutured primarily. The flap was successful in 90% of the cases (101 of 112 cases). Postoperatively, 94% of the cases (60 of 64 cases) of reconstructed tongue had good deglutition and 78% of the cases (50 of 64 cases) gave satisfactory enunciation. IHMCF is a new, versatile, reliable, and convenient flap suitable for repairing the defects in and around the oral cavity, particularly in the tongue, even in aged and weak patients.