Ultrasound-Guided Cradle-Like Infiltrative Anesthesia for Percutaneous Transluminal Angioplasty of Stenotic Autogenous Arteriovenous Hemodialysis Access.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is an effective treatment for autogenous arteriovenous hemodialysis access (AAVA) stenosis; however, it causes pain in most cases. Therefore, safe and effective anesthesia for PTA is required. METHODS: We introduced a method of ultrasound-guided cradle-like infiltration anesthesia (UCIA) to administer analgesia during PTA. Using ultrasound guidance, 1% lidocaine was injected into the bilateral and inferior perivascular spaces of the stenosis to form a cradle-like region. In this study, 100 consecutive patients were divided into two groups, and the analgesic effect of UCIA was evaluated using a numerical rating scale with non-ultrasound-guided infiltration anesthesia as a control. Meanwhile, we compared the effect of PTA between the two groups with the postoperative internal diameter of the stenosis. RESULTS: The numerical rating scale score was 4.6 ± 1.9 and 2.0 ± 1.6 (P < 0.001) in UCIA group and non-ultrasound-guided infiltration anesthesia group, respectively. The postoperative internal diameter of stenosis was 3.9 ± 0.6 mm and 4.1 ± 0.7 mm (P = 0.113); the postoperative AAVA flow volume was 627 ± 176 mL/min and 644 ± 145 mL/min (P = 0.600). CONCLUSIONS: This study preliminarily showed that UCIA is effective and safe for the analgesia of AAVA PTA.

The prognostic value of IL-8 for the death of severe or critical patients with COVID-19.

ABSTRACT: Inflammation has been believed to contribute to coronavirus disease 2019 (COVID-19). Risk factors for death of COVID-19 pneumonia have not yet been well established.In this retrospective cohort study, we included the deceased patients in COVID-19 specialized ICU with laboratory-confirmed COVID-19 from Guanggu hospital area of Tongji Hospital from February 8th to March 30th. Demographic, clinical, laboratory, and outcome data were extracted from electronic medical records using a standard data collection form. We used Spearman rank correlation and Cox regression analysis to explore the risk factors associated with in-hospital death, especially the association between inflammatory cytokines and death.A total of 205 severe/critical COVID-19 pneumonia patients were admitted in the COVID-19 specialized ICU and 75 deceased patients were included in the final analysis. The median age of the deceasing patients was 70 years (IQR 65-79). The common symptoms were fever (78.9%), cough (70.4%), and expectoration (39.4%). The BNP and CRP levels were far beyond the normal reference range. In the Spearman rank correlation analysis, IL-8 was found to be significantly associated with the time from onset to death (rs= -0.30, P = .034) and that from admission to death (rs= -0.32, P = .019). Cox regression showed after adjusting age and sex, IL-8 levels were still significantly associated with the time from onset to death (P = .003) and that from admission to death (P  = .01).IL-8 levels were associated with in-hospital death in severe/critical COVID-19 patients, which could help clinicians to identify patients with high risk of death at an early stage.

The associations between fasting plasma glucose levels and mortality of COVID-19 in patients without diabetes.

AIMS: Coronavirus disease 2019 (COVID-19) which is a novel pneumonia can rapidly progress to acute respiratory distress syndrome, septic shock, and multiple organ dysfunction syndrome. It has appeared in 196 countries around the world. We aimed to clarify the associations between fasting plasma glucose levels and mortality of COVID-19 in patients without diabetes. METHODS: We performed a retrospective, single-center study of 151 patients without diabetes in Tongji Hospital from January 1, 2020 to February 28, 2020. Past medical histories, clinical features and laboratory parameters were collected in these patients. RESULTS: Compared with survivors, non-survivors were more likely to have underlying medical conditions including hypertension and chronic pulmonary diseases. Non-survivors had higher C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-2R, IL-6, IL-8 and, tumor necrosis factor-α (TNF-α) levels, while lower lymphocyte counts as compared with those of survivors (all P<0.05). Besides, patients with higher fasting plasma glucose (FPG) had higher IL-6, IL-8, CRP levels and mortality; while lower lymphocyte counts. After adjusting for age and gender, each tertile increment of FPG levels conferred 3.54-fold higher risks of death (odds ratio, 3.54; 95% confidential interval, 1.25-10.06, P=0.018). CONCLUSIONS: Non-survivors combined with more comorbidities, more severe infection, and worse liver, kidney and cardiac function in patients without diabetes. Additionally, fasting plasma glucose levels were significantly associated with the risk of death in patients even with normal FPG and HbA1c levels.

[Therapeutic hypothermia reduced brain damage on rats after cardiopulmonary resuscitation by activating III-type PI3K pathway to increase autophagy].

OBJECTIVE: To investigate the effect of III-type phosphatidylinositide 3 kinase (PI3K) pathway adjusting autophagy on brain damage mechanism after cardiopulmonary resuscitation (CPR) and hypothermia treatment. METHODS: The asphyxia induce cardiac arrest-CPR model was reproduced on healthy male Sprague-Dawley (SD) rats. Sixty rats after restoration of spontaneous circulation (ROSC) were randomly divided into normothermia group, therapeutic hypothermia group and PI3K inhibitor 3-methyl adenine (3-MA) pretreatment group, differentiated by 24 hours and 48 hours after ROSC. Each group had 10 rats at each time point. The anal temperature in the normothermia group was maintained at (37.0±0.2) centigrade, and the rats in the hypothermia group were given cooling treatment immediately after ROSC, and the target rectal temperature was 32-34 centigrade. In the 3-MA pretreatment group, 10 mmol/L 3-MA 5 µL was injected into the ventricle 20 minutes before asphyxia, and other groups were given the same amount of normal saline. Ten rats without CPR were included in Sham group only received anesthesia and catheterization. The rats were sacrificed at 24 hours and 48 hours after ROSC respectively, and the brain tissues were harvested, the brain water content (BWC) was measured by dry-wet weight method. Western Blot was used to determine the autophagy related proteins Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3), apoptosis related proteins Bcl-2 and caspase-3, and the III-type PI3K pathway proteins Vps34 and Atg14. Ultrastructural changes in brain tissue were observed with transmission electron microscope. Neurological deficit scores (NDS) was obtained in each group at 48 hours after ROSC. RESULTS: Compared with Sham group, the cortex at 24 hours after ROSC in normothermic group showed obvious edema, apoptosis and autophagy began to appear under transmission electron microscope, and the expressions of autophagy, apoptosis and III- type PI3K-related proteins in brain tissue were significantly increased in a time-dependent manner, and the neurological function at 48 hours after ROSC was significantly damaged. After hypothermia intervention, brain edema of rats was significantly reduced, no obvious apoptosis was found, but autophagy was increased, the expressions of autophagy-related proteins Vps34, Atg14 and III-type PI3K-related proteins Beclin-1 and LC3 at 48 hours after ROSC were further higher than those of normothermic group (Vps34/GAPDH: 0.25±0.03 vs. 0.15±0.04, Atg14/GAPDH: 0.12±0.03 vs. 0.05±0.04, Beclin-1/GAPDH: 0.060±0.002 vs. 0.018±0.002, LC3 -II/GAPDH: 0.160±0.010 vs. 0.050±0.010, all P < 0.05), the expressions of apoptosis related proteins Bcl-2 and caspase-3 were significantly lowered (Bcl-2/GAPDH: 0.05±0.03 vs. 0.20±0.04, caspase-3/GAPDH: 0.050±0.002 vs. 0.140±0.015, both P < 0.05), neurological function was significantly improved (NDS: 157±85 vs. 343±198, P < 0.05). Pretreatment with 3-MA inhibited the protective effect of hypothermia on brain tissues. The expressions of Vps34, Atg14, Beclin-1 and LC3 in brain tissues at 48 hours after ROSC in 3-MA pretreatment group was significantly lower than those in the hypothermia group (Vps34/GAPDH: 0.18±0.03 vs. 0.25±0.03, Atg14/GAPDH: 0.07±0.04 vs. 0.12±0.03, Beclin-1/GAPDH: 0.015±0.003 vs. 0.060±0.002, LC3-II/GAPDH: 0.045±0.030 vs. 0.160±0.010, all P < 0.05), the expressions of Bcl-2 and caspase-3 were significantly increased (Bcl-2/GAPDH: 0.15±0.04 vs. 0.05±0.03, caspase-3/GAPDH: 0.120±0.015 vs. 0.050±0.002, both P < 0.05), and NDS score was significantly increased (341±208 vs. 157±85, P < 0.05). CONCLUSIONS: Hypothermia treatment reduced brain edema and ameliorated brain function after CPR, which might be related to increase autophagy and inhibit apoptosis adjustment by activating III-type PI3K pathway.

Lack of microRNA-155 ameliorates renal fibrosis by targeting PDE3A/TGF-ß1/Smad signaling in mice with obstructive nephropathy.

Although microRNA-155 (miR-155) is implicated in the pathogenesis of several fibrotic diseases, information regarding its functional role in renal fibrosis is limited. The current study aims to investigate the effects of miR-155 on renal fibrosis in unilateral ureteral occlusion (UUO) mice. MiR-155 level was significantly increased in renal tissues of UUO mice and TGF-ß1-treated HK2 cells. Masson's trichrome staining showed that delivery of adeno-associated virus encoding miR-155 inhibitor led to a decrease in renal fibrosis induced by UUO. The increased expression of plasminogen activator inhibitor type 1, collagen III and collagen IV was also inhibited after miR-155 inhibition. In addition, miR-155 knockdown also prevented TGF-ß1-induced epithelial-mesenchymal transition, concomitantly with a restoration of E-cadherin expression and a decrease of vimentin expression. Computational analysis revealed that miR-155 directly targets at 3'UTR of PDE3A. Overexpression of miR-155 suppressed the luciferase activity and protein expression of PDE3A, whereas inhibition of miR-155 increased PDE3A luciferase activity and expression. Furthermore, miR-155 inhibited TGF-ß1-induced the increase of TGF-ß1 expression and Smad-2/3 phosphorylation in HK2 cells. In contrast, knockdown of PDE3A reversed the effect of miR-155 inhibition on TGF-ß1 expression. This study demonstrates that knockdown of miR-155 attenuates renal fibrosis via inhibiting TGF-ß1/Smad signaling activation by targeting the upstream molecule PDE3A. This study suggests that miR-155 inhibition may be a novel therapeutic approach for preventing fibrotic kidney diseases.

Prognostic comparison of goal-oriented hemoperfusion and routine hemoperfusion combined with continuous venovenous hemofiltration for paraquat poisoning.

Objective To investigate the impact of goal-oriented hemoperfusion (HP) with monitoring of the paraquat concentration on the prognosis of patients with acute paraquat poisoning. Methods This prospective observational study involved patients with acute paraquat poisoning admitted from March 2012 to September 2015. The patients received either goal-oriented or routine HP. All other treatments were the same between the two groups. The primary endpoint was 28-day mortality after poisoning. The secondary endpoints were the incidence of organ dysfunction within 7 days and 7-day mortality. Results Eighty-four patients were enrolled (49 in the control group and 35 in the goal-oriented group). The two groups were similar in terms of clinical characteristics. There was no significant difference in the incidence of organ dysfunction between the two groups within 1 week of admission. Mortality on day 7 was significantly lower in the goal-oriented than control group, but there was no difference on day 28. However, 28-day mortality was significantly lower in the goal-oriented group among patients with an oral dose of ≤50 ml. Conclusions HP with monitoring of the urine paraquat concentration as goal-oriented therapy can reduce the early mortality of paraquat poisoning.

Inhibition of farnesyl pyrophosphate synthase improves pressure overload induced chronic cardiac remodeling.

Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. In our previous studies, we find that inhibition of FPPS attenuates angiotensin II-induced cardiac hypertrophy and fibrosis by suppressing RhoA while FPPS and Ras are up-regulated in pressure overload rats. In this study, we evaluate the effects and mechanisms of FPPS inhibition in pressure overload mice. Male FPPS-small interfering RNA (SiRNA) transgenic (Tg) mice and non-transgenic littermate control (NLC) were randomly divided into suprarenal abdominal aortic constriction (AAC) group and sham operation group. 12 weeks following AAC, mice were sacrificed by cervical dislocation. Histological and echocardiographic assessments showed that inhibition of FPPS improved chronic cardiac remodeling which was induced by AAC. The reductions of Ras farnesylation and GTP-Ras, as well as their downstream extracellular signal-related kinases 1/2 (ERK1/2) expression were observed in the heart of Tg-AAC mice compared with NLC-AAC mice, along with the reduction of fetal gene expression. We provide here important experimental evidence that inhibition of FPPS improves AAC induced chronic cardiac remodeling and fibrosis by the reduction of farnesylated Ras and the downregulation of Ras-ERK1/2 pathway.

Mild hypothermia in improving multiple organ dysfunction after cardiac arrest.

BACKGROUND: Resuscitation after cardiac arrest (CA) with a whole-body ischemia-reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest. METHODS: The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the rectum) over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the first 72 hours after recovery of spontaneous circulation (ROSC). RESULTS: At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not significantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group. CONCLUSION: In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.