Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Pneumococcal vaccine promotes the proliferation of CRTH2 (CD4+CD294+ Th2)cells / 中国感染控制杂志

Objective To study the proliferation of CRTH2 (CD4+ CD294+ Th2)cells promoted by pneumococcal vaccine through antigen presentation of dendritic cells (DCs),so as to provide a new approach for amplification and sorting of Th2 cells.Methods CDs induced from peripheral blood mononuclear cells were cocultured with T lym-phocytes after loading pneumococcal vaccine antigen,mixed lymphocyte reaction (MLR)was detected by cell count-ing kit-8(CCK8),DCs and CRTH2 cells were analyzed by flow cytometry.Results Pneumococcal vaccine could promote the maturation of DCs,together with TNF-a,it was adjuvant for maturation of DCs.Pneumococcal vaccine antigen-loaded DCs could increase the rate of subsets of CRTH2 cells on day 5([0.93±0.10]%)compared with day 1([0.70±0.02]%),and absolute number also increased (both P <0.05).Conclusion Amplification of CRTH2 cells can be greatly promoted by pneumococcal vaccine antigen-loaded DCs,which might be one of the effective way to induce amplification of Th2 cells.

Pneumococcal vaccine promotes the proliferation of CRTH2 (CD4+CD294+ Th2)cells / 中国感染控制杂志

Objective To study the proliferation of CRTH2 (CD4+ CD294+ Th2)cells promoted by pneumococcal vaccine through antigen presentation of dendritic cells (DCs),so as to provide a new approach for amplification and sorting of Th2 cells.Methods CDs induced from peripheral blood mononuclear cells were cocultured with T lym-phocytes after loading pneumococcal vaccine antigen,mixed lymphocyte reaction (MLR)was detected by cell count-ing kit-8(CCK8),DCs and CRTH2 cells were analyzed by flow cytometry.Results Pneumococcal vaccine could promote the maturation of DCs,together with TNF-a,it was adjuvant for maturation of DCs.Pneumococcal vaccine antigen-loaded DCs could increase the rate of subsets of CRTH2 cells on day 5([0.93±0.10]%)compared with day 1([0.70±0.02]%),and absolute number also increased (both P <0.05).Conclusion Amplification of CRTH2 cells can be greatly promoted by pneumococcal vaccine antigen-loaded DCs,which might be one of the effective way to induce amplification of Th2 cells.

Determination and correlation analysis of contents of putrescine, cadaverine, and histamine in necrotic tissue, blood, and urine of patients with diabetic foot / 中华烧伤杂志

<p><b>OBJECTIVE</b>To determine and perform a correlation analysis of the contents of putrescine, cadaverine, and histamine in necrotic tissue, blood, and urine of patients with diabetic foot (DF).</p><p><b>METHODS</b>Ten patients with severe wet necrotizing DF hospitalized from January 2011 to January 2012 were assigned as group DF, and 10 orthopedic patients with scar but without diabetes or skin ulcer hospitalized in the same period were assigned as control group. Samples of necrotic tissue from feet of patients in group DF and normal tissue from extremities of patients in control group, and samples of blood and 24-hour urine of patients in both groups were collected, and the amount of each sample was 10 mL. Contents of putrescine, cadaverine, and histamine were determined with high performance liquid chromatography-mass spectrometry. The data got from the determination of blood and urine were processed with t test, and those from necrotic or normal tissue with Wilcoxon rank sum test. The correlation of contents of polyamines between necrotic tissue and blood, blood and urine were processed with simple linear regression analysis.</p><p><b>RESULTS</b>(1) Contents of putrescine, cadaverine, and histamine in the necrotic tissue of group DF were (186.1 ± 26.8), (78.553 ± 12.441), (33 ± 10) mg/kg, which were significantly higher than those in normal tissue of control group [(2.2 ± 1.2), (1.168 ± 0.014), 0 mg/kg, with Z values respectively -3.780, -3.781, -4.038, P values all below 0.01]. The content of putrescine in necrotic tissue of group DF was significantly higher than those of cadaverine and histamine (with Z values respectively -3.780, -3.630, P values all below 0.01). (2) Contents of putrescine, cadaverine, and histamine in the blood of group DF were (0.075 ± 0.013), (0.022 ± 0.003), (0.052 ± 0.014) mg/L, and they were significantly higher than those in the blood of control group [(0.014 ± 0.009), (0.013 ± 0.003), (0.016 ± 0.008) mg/L, with t values respectively 6.591, 2.207, 3.568, P < 0.05 or P<0.01]. The content of putrescine in the blood of group DF was significantly higher than those of cadaverine and histamine (with t values respectively 13.204, 3.096, P values all below 0.01). (3) Contents of putrescine, cadaverine, and histamine in the urine of group DF were (0.735 ± 0.088), (0.450 ± 0.012), (0.1623 ± 0.0091) mg/L, and only the contents of putrescine and cadaverine were significantly higher than those in the urine of control group [(0.050 ± 0.014), (0.035 ± 0.007) mg/L, with t values respectively 3.270, 4.705, P<0.05 or P<0.01]. The content of putrescine in the urine of group DF was significantly higher than that of cadaverine (t = 6.686, P < 0.01). (4) There were significant and positive correlations in contents of putrescine, cadaverine, and histamine between necrotic tissue and blood in patients of group DF (with r values respectively 0.981, 0.994, 0.821, P values all below 0.01). There were no significant correlations in contents of putrescine, cadaverine, and histamine between blood and urine in patients of group DF (with r values respectively 0.150, 0.239, 0.177, P values all above 0.05).</p><p><b>CONCLUSIONS</b>Putrescine, cadaverine, and histamine exist in the necrotic tissue of patients with DF in high concentrations, among which putrescine predominates. These polyamines can be absorbed into the blood through wound and excreted through the urine.</p>

Influence of exogenous putrescine and cadaverine on pro-inflammatory factors in the peripheral blood of rabbits / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the influence of exogenous putrescine and cadaverine on pro-inflammatory factors in the peripheral blood of rabbits.</p><p><b>METHODS</b>Forty ordinary adult New Zealand rabbits were divided into saline, necrotic tissue homogenate (NTH), putrescine, and cadaverine groups according to the random number table, with 10 rabbits in each group. Saline, NTH, 10 g/L putrescine, and 10 g/L cadaverine were respectively peritoneally injected into rabbits of corresponding group in the amount of 1 mL/kg. The blood sample in the volume of 2 mL was collected from the central artery of rabbit ears before injection and at 2, 6, 12, 24, 30, 36, 48, 60 hours post injection (PIH). Contents of TNF-α, IL-1, and IL-6 in the serum were determined with enzyme-linked immunosorbent assay. Data were processed with repeated measurement data analysis of variance and Spearman correlation analysis, and cubic model curve was applied in curve fitting for the contents of inflammatory factors.</p><p><b>RESULTS</b>(1) The serum contents of TNF-α, IL-1, and IL-6 were increased in NTH, putrescine, and cadaverine groups in different degrees at most post injection time points. There was no significant change in the concentrations of the three pro-inflammatory factors in saline group, and they were significantly lower than those of the other three groups at most post injection time points (with F values from 3.49 to 13.58, P values all below 0.05). The serum contents of TNF-α, IL-1, and IL-6 in putrescine group began to increase at PIH 2, 6, and 6, which was similar to the trend of NTH group, but the changes were delayed compared with those of cadaverine group(all at PIH 2). The peak values of TNF-α, IL-1, and IL-6 in putrescine group were respectively (339 ± 36), (518 ± 44), and (265.9 ± 33.5) pg/mL, which were significantly lower than those of cadaverine group [ (476 ± 86), (539 ± 22), and (309.4 ± 27.1) pg/mL], with F values respectively 5.11, 1.90, and 5.56, P values all below 0.05. (2) The period of time in which contents of TNF-α, IL-1, and IL-6 began to increase (PIH 3-4) and the peaking time of the three pro-inflammatory cytokines (PIH 18-30) in putrescine group appeared later than those of cadaverine group (PIH 2 and 12-30). The duration of peaking time of the three pro-inflammatory cytokines in putrescine group was shorter than that of cadaverine group (PIH 18-30 vs. PIH 12-30). The increasing period and the duration of peaking time of TNF-α, IL-1, and IL-6 in putrescine group were close to those of NTH group (PIH 3-5 and 18-30). The correlation coefficient test analysis showed that the trends of changes in contents of three pro-inflammatory cytokines in putrescine group were significantly correlated with those of NTH group (r(TNF-α) = 0.933, P < 0.01; r(IL-1) = 0.967, P < 0.01; r(IL-6) = 0.950, P < 0.01). The obvious correlation between cadaverine group and NTH group was only found in the contents of IL-1 and IL-6 (r(IL-1) = 0.913, P < 0.01; r(IL-6) = 0.883, P < 0.05).</p><p><b>CONCLUSIONS</b>Both exogenous putrescine and cadaverine can cause inflammatory reaction in rabbits. The trend of the inflammatory reaction induced by putrescine was similar with that by NTH, suggesting that putrescine may play a leading role in the inflammatory reaction induced by necrotic tissue decomposition.</p>

Effect of intralipid for ameliorating protein loss in severe burned patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of intralipid on protein consumption in severe burned patients. METHODS; Sixty-seven nonoperative patients with severe burns were divided into Intralipid treatment group and non-intralipid treatment group (control group), and the former was treated with 20% intralipid (500 ml once a day) from postburn day 4 for 10 consecutive days. Venous blood samples were collected from these patients for testing total protein, albumin, total cholesterol and triglyceride on postburn days 1, 7 and 14, respectively.</p><p><b>RESULTS</b>The levels of total protein, albumin, total cholesterol and triglyceride were within normal range on postburn day 1 in both groups, and only the albumin level was lowered in the groups on day 7 but at comparable magnitudes (32+/-4.83 vs 31+/-5.04 g/L, P<0.05). In contrast, the levels of total protein, albumin, total cholesterol and triglyceride were below the normal range on postburn day 14 in both groups, but intralipid treatment group showed more albumin loss than the control group (28+/-6.46 vs 23+/-7.03 g/L, P<0.01).</p><p><b>CONCLUSION</b>Intralipid (20%) provides good energy source to ameliorate albumin loss in severe burned patients.</p>

Morphological changes in intestinal villi after severe burns in rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the morphological changes in intestinal villi after severe burns in rats, so as to explore its possible relationship with enteral bacterial translocation.</p><p><b>METHODS</b>Fifty Wistar rats were employed in the study, 10 of them were assigned to the control group (C). The rest 40 rats were subjected to 30% TBSA full-thickness scalding (burn group, B). 4 ml/100 g normal saline was given intra-peritoneally to the injured rats. The changes of the caliber of the central chyliferous vessel, the intestinal water content and the mucosal morphology of the terminal ileum were determined in the rats in C group and in B group at 8, 12, 24 and 48 postburn hours. The morphology of villi was observed with scanning electron microscope and light microscope.</p><p><b>RESULTS</b>The ileal villi appeared normal in C group. The central chyliferous vessel dilated persistently in rats of B group at all postburn time points, and dilatation was more evident in B group compared with control group (P < 0.01). At the same time an abundant amount of lymph was observed in the central chyliferous vessel. The intestinal water contents decreased to (70.5 +/- 2.2)% and (69.5 +/- 3.1)% in rats of B group at 8 and 12 PBHs, respectively, and they were obviously lower than that in C group (76.9 +/- 1.5)%, (P < 0.01). The intestinal water content in B group was similar to that in C group at 24 and 48 PBH (P > 0.05).</p><p><b>CONCLUSION</b>The morphological changes in the intestinal villi of rats with severe burn injury may predispose the invasion of enteral toxin and bacteria. Intestinal lymphatics can be an important route for enteral bacterial translocation. The water reabsorption of the intestinal mucosa can be transiently enhanced during early postburn stage.</p>

Clinical evaluation of the postburn retention and the metabolism of Imipenem in the third space / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the half life and retention of Imipenem in the third space.</p><p><b>METHODS</b>Eight severely burned patients and eight healthy volunteers were enrolled as the burn group (B) and normal control group (C), respectively. HPLC (high performance liquid chromatography) was employed to determine the contents of Imipenem in the plasma, subeschar tissue fluid (STF) and the changes in its pharmacokinetics. Furthermore, the Imipenem content in the third space was calculated according to the systemic edema degree.</p><p><b>RESULTS</b>The half life of Imipenem in STF (2.53 h) was longer than that in plasma (1.73 h), P < 0.05). The Imipenem content in STF increased gradually along with the lapse of time after repeated intravenous infusion of Imipenem, and at the same the total content of imipenem was increased significantly in the third space.</p><p><b>CONCLUSION</b>There was antibiotic retention in the third space after severe burn injury, and a prolonged action of the drug could be expected when the drug re-entered the blood stream.</p>