Efficacy and safety of methylene blue in patients with vasodilatory shock: A systematic review and meta-analysis.

Background: The role of methylene blue (MB) in patients with vasodilatory shock is unclear. The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of MB in patients with vasodilatory shock. Methods: We searched MEDLINE at PubMed, Embase, Web of Science, Cochrane, CNKI, CBM and Wanfang Medical databases for all observational and intervention studies comparing the effect of MB vs. control in vasodilatory shock patients. This study was performed in accordance with the PRISMA statement. There were no language restrictions for inclusion. Results: A total of 15 studies with 832 patients were included. Pooled data demonstrated that administration of MB along with vasopressors significantly reduced mortality [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.34 to 0.85, P = 0.008; I 2 = 7%]. This benefit in mortality rate was also seen in a subgroup analysis including randomized controlled trials and quasi-randomized controlled trials. In addition, the vasopressor requirement was reduced in the MB group [mean difference (MD) -0.77, 95%CI -1.26 to -0.28, P = 0.002; I 2 = 80%]. Regarding hemodynamics, MB increased the mean arterial pressure, heart rate and peripheral vascular resistance. In respect to organ function, MB was associated with a lower incidence of renal failure, while in regards to oxygen metabolism, it was linked to reduced lactate levels. MB had no effect on the other outcomes and no serious side effects. Conclusions: Concomitant administration of MB and vasopressors improved hemodynamics, decreased vasopressor requirements, reduced lactate levels, and improved survival in patients with vasodilatory shock. However, further studies are required to confirm these findings. Systematic review registration: Identifier: CRD42021281847.

Repair of coronary artery ostium with a ring-shaped bovine pericardial patch.

As an approach to coronary artery ostial injury in type A aortic dissection and infective endocarditis, we describe a technique of coronary ostial repair using a ring-shaped bovine pericardial patch. The inner and outer rims of the patch were sutured to the involved coronary ostium (to close the ostial tear) and to the aortic wall (to cover the sinus), respectively. Four patients were successfully managed and computed tomographic coronary arteriogram at follow-up showed patent coronary ostia and arteries. The favourable preliminary results imply that this technique is a simple, safe and effective approach to coronary ostial repair in patients with type A aortic dissection or infective endocarditis.

Risk Factors for Postoperative Mortality in Patients with Acute Stanford Type A Aortic Dissection.

OBJECTIVE: The present study explored the risk factors of postoperative mortality in patients with acute Stanford type A aortic dissection (AD). METHODS: The study included 149 patients with acute Stanford type A AD who were treated at the Fourth Hospital of Hebei Medical University, China, from October 2016 to October 2018. The patients were divided into a death (n = 42) and survival group (n = 107) according to individual prognosis. Univariate analysis of all possible related risk factors was conducted; multivariate logistic regression analysis of the potential risk factors that showed statistical differences in the univariate analysis was also performed. RESULTS: The results of the univariate analysis showed that a body mass index (BMI) ≥25 kg/m2, surgery duration, duration of cardiopulmonary bypass, duration of cardiopulmonary bypass assistance, total transfusion of red blood cells, postoperative APACHE II score, sequential organ failure assessment (SOFA) score, low cardiac output, acute kidney injury (AKI), hypoxemia, diffuse intravascular coagulation (DIC), hepatic failure and other related complications, as well as postoperative stay duration in the intensive care unit (ICU), were closely correlated with a poor prognosis among patients. Multivariate logistic regression analysis showed that a BMI ≥25 kg/m2, SOFA score >8, duration of cardiopulmonary bypass assistance >70 minutes, postoperative low cardiac output, and postoperative DIC were independent risk factors for postoperative death in patients with acute Stanford type A AD. CONCLUSION: A BMI ≥25 kg/m2, SOFA score >8, duration of cardiopulmonary bypass assistance >70 min, postoperative DIC, and postoperative low cardiac output were the independent risk factors for postoperative death in acute Stanford type A AD. Intraoperative blood transfusion, postoperative hepatic failure, and AKI, among others, correlated with an increased risk of death but were not independent risk factors for death.

A preliminary study on the postoperative survival of patients given aspirin after resection for squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia.

BACKGROUND: We examined the effect of aspirin on survival following resection for squamous cell carcinoma (SCC) of the esophagus or adenocarcinoma of the gastric cardia. METHODS: Patients who underwent esophagectomy for these cancers between May 2000 and December 2002 were allocated to one of three groups and given daily either a low dose of aspirin, placebo, or no tablets. RESULTS: The 5-year survival for all patients on aspirin (445) was 51.2%, placebo (658) 41%, and no tablet (495) 42.3% (P = 0.04 for difference between treatments). The 5-year survival for all SCC patients on aspirin (267) was 49.8%, placebo (433) 42.2%, and no tablet (343) 41.2% (P = 0.26). There was a significant improvement in survival for patients with adenocarcinoma of the cardia on aspirin compared with the two control groups combined (P = 0.029). Survival for T2N0M0 SCC patients was significantly improved with aspirin (71) compared with placebo (167) or no tablet (134) (P = 0.0004). However, there was no significant difference between the survival curves for T2N0M0 adenocarcinoma patients on aspirin (21) and the two control groups combined (65) (P = 0.29). CONCLUSIONS: The results of this preliminary study support further investigation of aspirin as adjuvant therapy to improve survival in subsets of postesophagectomy patients.

NS-398 induces apoptosis in human esophageal cancer cells through inhibition of NF-kappaB downstream regulation of cyclooxygenase-2.

Although non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to have cancer-preventive effects and induce apoptosis of cancer cells, the mechanism of their effects is not clearly known. We studied the mechanism in human esophageal cancer cell line TE13. The esophageal squamous cell carcinoma cell line TE-13 was cultured with NS-398 at different concentrations or for different times. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Prostaglandin F(1alpha) was determined with radioimmunoassay. Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. NS-398 significantly inhibited cell proliferation and induced apoptosis at concentrations of 0.001, 0.01, 1, and 100 micromol/L. NS-398 dose-dependently decreased the levels of COX-2 mRNA, COX-2 protein, nuclear NF-kappaB protein and production of PGF(1alpha) and increased the cytoplasmic IkappaB protein. In conclusion, NS-398 inhibits the proliferation of, and induced apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic IkappaB.

The effects of a COX-2 inhibitor meloxicam on squamous cell carcinoma of the esophagus in vivo.

Our previous study showed that aspirin induced apoptosis of esophageal cancer cells in vitro by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2. The purpose of this study was to determine if similar changes occurred in vivo in the tumors of patients with SCC of the esophagus who were given a preferential COX-2 inhibitor, meloxicam. Fifty-three patients who had an esophagectomy for SCC were allocated randomly to either a Treatment group (n = 25) or a control group (n = 28). Patients in the Treatment group were given 7.5 mg/day of meloxicam, for between 10 and 14 days before surgery. Patients in the control group did not take any type of NSAID during this time interval. Samples of the tumor taken from the resected specimens were collected. Proliferation and apoptosis were measured by flow cytometry. The concentration of 6-keto-prostaglandin F(1)alpha in cancer tissue was determined by radio-immuno-assay. Expression of COX-2 mRNA was measured with RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic I kappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. There were significantly more apoptotic cells in the tumors of patients who were using meloxicam. It also decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic I kappaB protein in the cancer. We conclude that meloxicam induces apoptosis in SCC of the esophagus in vivo by inhibiting the pathway of NF-kappaB downstream regulation of COX-2.

[Effect of diallyl trisulfide on tumor necrosis factor-alpha expression and nuclear factor-KappaB activity in mice with acute lung injury induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-KappaB (NF-KappaB) activity in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: ALI murine model was reproduced by injection of LPS intraperitoneally. Mice were randomly divided into normal saline control group, ALI group, DATS prevention group, DATS treatment group, and DATS control group. The TNF-alpha levels in the serum and in the supernatant of lung homogenates were measured with enzyme linked immunoadsorbent assay (ELISA). The expression of TNF-alpha mRNA in the lung tissues was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-KappaB activity in the lung tissues was detected by electrophoresis mobility shift assay (EMSA). RESULTS: The levels of TNF-alpha induced by LPS in the serum and the supernatant of lung homogenates were increased markedly at 2 hours in ALI group (both P<0.01), and decreased at 6 hours, but they were still higher than those of the control groups (all P<0.01). They were reduced in DATS prevention group at 2 and 6 hours compared with those of ALI group (P<0.05 or P<0.01), but no change was noted in DATS treatment group (all P>0.05). The expression of TNF-alpha mRNA in the lung tissues of ALI group increased markedly at 2 hours compared with those of control groups (both P<0.01), and it could be down-regulated by pretreatment with DATS (P<0.05). No change in DATS was found in treatment group. NF-KappaB activity in the lung tissue increased in ALI group compared with that of control groups (both P<0.05), and it was markedly reduced in DATS prevention group (P<0.05), but no change was found in DATS treatment group. CONCLUSION: Pretreatment of DATS for ALI in mice could inhibit NF-KappaB activity, TNF-alpha mRNA expression in lung tissues, and decrease the release of TNF-alpha in the serum and the lung homogenates, and they might be the underlying mechanisms of prevention of the occurrence of ALI by DATS.

Aspirin induces apoptosis in oesophageal cancer cells by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2.

BACKGROUND: Aspirin has potential in the prevention or treatment of oesophageal cancer, the seventh most common cancer in the world, but its mechanism of action is still not certain. METHODS: The oesophageal squamous cell carcinoma cell line TE-13 was cultured with aspirin at different concentrations or for different times. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. RESULTS: Aspirin significantly inhibited cell proliferation and induced apoptosis at concentrations of 1, 4, 8 mmol/L. Aspirin dose-dependently decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic IkappaB protein. CONCLUSION: We conclude that aspirin inhibits the proliferation of, and induced apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic IkappaB. These results support the further investigation of the cyclooxygenase pathway in investigating the potential of aspirin and similar drugs in cancer prevention and therapy.

Effect of cholecystokinin octapeptide on tumor necrosis factor alpha transcription and nuclear factor-kappaB activity induced by lipopolysaccharide in rat pulmonary interstitial macrophages.

AIM: To elucidate the anti-inflammatory mechanism of an intestinal neuropeptide, sulfated cholecystokinin octapeptide (sCCK-8), the effects of sCCK-8 on lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) mRNA expression and NF-kappaB activity in pulmonary interstitial macrophages (PIMs) were studied. METHODS: PIMs from rat were stimulated with LPS (1 mg.L(-1)) in the presence or absence of sCCK-8 (10(-8)-10(-6)mol.L(-1)) or/and CCK receptor antagonist proglumide (2 mg.L(-1)). The expression of TNF-alpha mRNA was assayed by reverse transcription polymerase chain reaction (RT-PCR) at 3h of the stimulation, and nuclear factor-kappaB (NF-kappaB) binding activity was analyzed by electrophoretic mobility shift assay (EMSA) at 1 h of stimulation. The IkappaBalpha protein level in the cytoplasma at 30 min of the stimulation was detected by Western blot. RESULTS: sCCK-8, at concentrations from 10(-8) mol.L(-1) to 10(-6) mol.L(-1) obviously inhibited LPS-induced TNF-alpha mRNA expression and NF-kappaB binding activity in a dose-dependent manner, P<0.05, P<0.01. Stimulation PIMs with LPS resulted in a reduction of IkappaBalpha protein level, P<0.01, which was elevated by sCCK-8, P<0.05. The effects of sCCK-8 on NF-kappaB activity and IkappaB protein level were attenuated by CCK receptor antagonist proglumide, P<0.01. CONCLUSION: sCCK-8 inhibits LPS-induced TNF-alpha mRNA expression by regulating NF-kappaB activity in rat PIMs, which is mediated through CCK receptors and inhibiting IkappaB-alpha degradation. This represents one of the anti-inflammatory mechanisms of sCCK-8.

[Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous oxygen saturation in patients with sepsis].

OBJECTIVE: To compare the efficacy of fluid resuscitation as guided by lactate clearance rate (LCR) and central venous oxygen saturation (ScvO2) in patients with sepsis. METHODS: A prospective randomized control study was conducted. Fifty patients diagnosed with severe sepsis or septic shock from January 2011 to February 2012 in department of critical care medicine of Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were randomly divided into two groups according to the sequence (each n=25): ScvO2 group and LCR group. After ICU admission, the patients were treated symptomatically timely, and fluid resuscitation was started as early as possible according to Surviving Sepsis Campaign guidance for management of severe sepsis and septic shock 2008. Central venous pressure (CVP)≥8 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure (MAP)≥65 mm Hg and ScvO2≥0.70 served as goal values to accomplish the fluid resuscitation therapy in ScvO2 group, while CVP≥8 mm Hg, MAP≥65 mm Hg, LCR≥10% served as goal value to accomplish the fluid resuscitation therapy in LCR group. The general condition and clinical characteristics on arrival in ICU, changes in CVP, MAP, ScvO2, lactate level and/or LCR before (0 hour) and 3, 6, 72 hours after the start of fluid resuscitation and the other related conditions during the therapy were recorded. RESULTS: There was no significant difference in general data or clinical characteristics before the start of therapy, occurrence of organ dysfunction, or treatment measures during different time periods after start of fluid resuscitation. Compared with the condition immediately before fluid resuscitation, at 3 hours after start of fluid resuscitation, CVP were improved in LCR and ScvO2 groups (8.58±1.17 mm Hg vs. 6.33±1.21 mm Hg, 9.08±2.43 mm Hg vs. 5.33±0.98 mm Hg, both P<0.05); at 6 hours after start of fluid resuscitation, heart rate (HR) and respiratory rate (RR) were lowered in LCR and ScvO2 groups (HR: 96±18 bpm vs. 127±13 bpm, 98±13 bpm vs. 116±19 bpm, RR: 23±3 times/min vs. 33±9 times/min, 24±5 times/min vs. 35±6 times/min, all P<0.05), oxygenation index (PaO2/FiO2) was increased in LCR and ScvO2 groups (179±41 mm Hg vs. 86±21 mm Hg, 202±33 mm Hg vs. 95±17 mm Hg, both P<0.05), and there was no significant difference in MAP in both groups. There was no significant difference in all indexes between two groups. In LCR group, 3 hours after start of fluid resuscitation, lactate level was significantly decreased (2.81±0.18 mmol/L vs. 3.43±1.31 mmol/L, P<0.05). Compared with the value 3 hours after start of fluid resuscitation, LCR was significantly improved at 6 hours and 72 hours after start of fluid resuscitation in LCR group [(42.69±8.75)%, (48.87±9.69)% vs. (20.32±4.58)%, both P<0.05]. Compared with that immediately before fluid resuscitation, ScvO2 was significant improved in ScvO2 group at 3 hours after start of fluid resuscitation (0.65±0.04 vs. 0.53±0.06, P<0.05). There was no significant difference in success rate of fluid resuscitation comparing that of 6 hours and that of 72 hours [6 hours: 72% (18/25) vs. 64% (16/25), χ(2)=0.368, P=0.762; 72 hours: 88% (22/25) vs. 88% (22/25) ,χ(2)=0.000, P=1.000], length of ICU stay (8±3 days vs. 10±4 days, t=0.533, P=0.874), length of hospital stay (29±11 days vs. 35±16 days, t=0.692, P=0.531), improvement rate [84% (21/25) vs. 76%(19/25), χ(2)=0.500, P=0.480] or 28-day mortality [20% (5/25) vs. 28% (7/25), χ(2)=0.439, P=0.742] between LCR and ScvO2 groups. CONCLUSIONS: Both LCR and ScvO2 can be taken as the index in confirming the endpoint of fluid resuscitation for patients with severe sepsis and septic shock. Fluid resuscitation therapy under the guidance of LCR is accurate and reliable in patients with severe sepsis and septic shock.