The effect of acetylsalicylic acid on pain and recurrence of endometriosis after surgery: A randomized controlled trial

Background: Reactive oxygen species (ROS) might increase growth and adhesion of endometrial cells in the peritoneal cavity, and lead to endometriosis. In this study the we evaluate the effect of an antioxidant, acetylsalicylic acid (aspirin), to determine whether aspirin administration to patients with endometriosis would affect pelvic pain and disease recurrence. Material and methods: This randomized controlled trial was conducted from March 2018 to March 2020 on women, 19 to 40 years of age, who were diagnosed with endometriosis after undergoing laparoscopic surgery. Study participants were randomly assigned to one of two groups, Oral contraceptive pills (OCP) and placebo or OCP and aspirin, which were administered daily for 6 months. Pelvic pain, dysmenorrhea, mass size, and menstrual bleeding were evaluated at 3 and 6 months. Results: There were 38 patients in the aspirin group and 49 participants in the placebo group. The mean dysmenorrhea Visual analog scale (VAS) score after 3 months was 2.24 in the aspirin group and 3.61 in the placebo group. After 6 months, the dysmenorrhea VAS scores were 0.68 (aspirin group) and 2.69 (placebo group) ( p = 0.005 and p = 0.00, respectively). Dyspareunia and pelvic pain showed significant reductions ( p = 0.00). Six patients in the control group and four patients in the aspirin group experienced lesion recurrence ( p = 0.45). Conclusion: The results suggest that aspirin, as an antioxidant, could effectively reduce pain in women with endometriosis. However, additional studies that enroll larger numbers of participants and long-term follow up will enable better evaluation of recurrence.

Ischemic Benefit and Hemorrhage Risk Of Ticagrelor-Aspirin Versus Aspirin In Patients With Acute Ischemic Stroke Or TIA

Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack (TIA), the Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) trial demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk TIA, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or non-hemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these two endpoints. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19%, 95%CI 0.31%-2.07%). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29%, 95% CI, 0.10-0.48%). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97%, 95% CI, 0.08%-1.87%). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild-moderate ischemic stroke or high-risk TIA, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. Registration: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03354429

Benefits and Risks Associated With Aspirin Use in Patients With Diabetes for the Primary Prevention of Cardiovascular Events and Mortality: A Meta-Analysis

PurposeA meta-analysis was conducted to assess the benefits and risks of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in adults with diabetes.MethodsAn extensive and systematic search was conducted in MEDLINE (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. Random-effects meta-analysis was used to calculate the pooled odds ratio for outcomes of cardiovascular events, death, and adverse events.FindingsA total of 8 studies were included with 32,024 patients with diabetes; 16,001 allocated to aspirin, and 16,023 allocated to the control group. There was no difference between aspirin and control groups with respect to all-cause mortality, cardiovascular mortality, or bleeding events. However, MACE was significantly lower in the aspirin group.ImplicationsAlthough aspirin has no significant risk on primary endpoints of cardiovascular events and bleeding outcomes in patients with diabetes compared to control, major adverse cardiovascular events (MACE) were significantly lower in the aspirin group. Further research on the use of aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research. Systematic Review Registrationidentifier [XU#/IRB/2020/1005].

Comparative effectiveness of combined antiplatelet treatments in acute minor ischaemic stroke

BackgroundNo study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel–aspirin) versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.MethodsWe identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel–aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months.ResultsAmong 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel–aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel–aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group (weighted HR: 0.82 (0.59–1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76–1.44)) or other combination group and the 3-month primary outcome.ConclusionOther combined antiplatelet treatment, compared with aspirin alone or clopidogrel–aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

Aspirin Use is Associated with Decreased Mortality in Patients with COVID-19: A Systematic Review and Meta-analysis

Background: Novel Corona Virus Disease 2019 (COVID-19) has resulted in more than three and half million deaths worldwide as of June 6, 2021. The role of aspirin in prevention of COVID-19 mortality has not been much studied. We aimed to study the relationship between aspirin use and covid-19 mortality. Methods: We searched PubMed, MEDLINE, EMBASE, and Cochrane database for studies from January 2019 till June 6, 2021 with inclusion criteria of RCT, Cohort study, studies reporting mortality, and comparison studies on aspirin versus non-aspirin. Statistical analysis was done with Review Manager 5.4 statistical software using the inverse variance method. We assessed the pooled hazard ratio (HR), and 95% confidence interval using the random effect model and I-squared test was used to determine statistical heterogeneity. Results: We included five retrospective cohort studies which met our inclusion criteria with total of 14065 participants in both groups. There were 6797 participants in the aspirin group and 7268 participants in the non-aspirin group. Our results show that the use of aspirin was associated with 53% decrease in mortality compared to non-aspirin in patients with COVID-19 (adjusted HR 0.47, 95% CI 0.35-0.63, P< 0.001, I2= 47%). In the analysis restricted to patients hospitalized for COVID-19, the use of aspirin was associated with a 49% reduction in the risk for in-hospital mortality (adjusted HR 0.51, 95% CI 0.33-0.80, P = 0.004, I2= 39%). Conclusions: Our results show that aspirin is associated with decrease in both overall mortality and in-hospital mortality in patients with COVID-19.

Effects of Aspirin on Myocardial Ischemia-Reperfusion Injury in Rats through STAT3 Signaling Pathway

Objective. To investigate the role and mechanism of aspirin in myocardial injury induced by myocardial ischemia-reperfusion in rats through STAT3 signaling pathway. Methods. Sixty rats were randomly divided into three groups: the sham operation group, MI/R group, and MI/R+aspirin group (aspirin group). The rats in the sham operation group did not ligate the LAD coronary artery, while the aspirin group ligated the LAD coronary artery, which caused the suture to be loosened after 30 minutes ischemia, and 60 mg/kg aspirin was injected into the tail vein 10 minutes before reperfusion. After three hours of reperfusion, the ultrasound system was used to collect hemodynamic parameters, including ejection fraction (EF%), shortening fraction (FS%), and left ventricular end-systolic pressure (LVESP%) and left ventricular end-diastolic pressure (LVEDP%). Finally, the rats were euthanized; then, blood samples were taken for biochemical examination, myocardial tissue was collected, and the left ventricle was used for subsequent experiments. The gene expression levels of Bax and Bcl-2 were detected by PCR. The protein expression levels of Bcl-2, Bax, p-JAK2, total JAK2, p-STAT3, and total STAT3 were detected by Western blot. Results. Compared with the sham operation group and the aspirin group, the area of myocardial infarction in the MI/R was significantly increased ( p < 0.05 ). In terms of hemodynamic parameters, LVEDP was significantly elevated in the MI/R group. The results of PCR showed that compared with the MI/R group, the mRNA expression of Bax in the aspirin group was significantly decreased, while that of Bcl-2 was significantly increased ( p < 0.05 ). Western blot analysis showed that compared with the MI/R group, aspirin pretreatment significantly increased the expression levels of p-STAT3 and p-JAK2 ( p < 0.05 ). Conclusion. The mechanism of aspirin preconditioning to protect the heart from MI/R injury appears to be related to JAK2/STAT3 and related to the activation of the signaling pathway.

Effects and safety of aspirin use in patients after cerebrovascular bypass procedures

ObjectSuperficial temporal artery to middle cerebral artery (STA-MCA) bypass is the most effective treatment for Moyamoya disease (MMD). In this study, we aimed to assess whether aspirin improves STA-MCA bypass patency and is safe in patients with MMD.MethodsWe performed a retrospective medical record review of patients with ischaemic-onset MMD who had undergone STA-MCA bypass at two hospitals between January 2011 and August 2018, to clarify the effects and safety of aspirin following STA-MCA bypass. The neurological status at the last follow-up (FU) was compared between patients with FU bypass patency and occlusion.ResultsAmong 217 identified patients (238 hemispheres), the mean age was 41.4±10.2 years, and 51.8% were male; the indications for STA-MCA bypass were stroke (48.2%), followed by a transient ischaemic attack (44.0%). Immediate bypass patency was confirmed in all cases. During the FU period (1.5±1.5 y), 15 cases were occluded at FU imaging, resulting in an overall cumulative patency rate of 94%. The patency rates were 93% and 94% in the short-term FU group (n=131, mean FU time 0.5±0.2 years) and long-term FU group (n=107, mean FU time 4.1±3.5 years), respectively. The STA-MCA bypass patency rate in the aspirin group was higher than that in the non-aspirin group (98.7% vs 89.7%; HR 1.57; 95% CI 1.106 to 2.235; p=0.012). No significant difference in the FU haemorrhagic events was observed between the aspirin and non-aspirin groups.ConclusionsAmong adult patients with ischaemic-onset MMD undergoing STA-MCA bypass procedures, aspirin might increase the bypass patency rate, without increasing the bleeding risk. FU bypass patency may be associated with a better outcome. Additional studies, especially carefully designed prospective studies, are needed to address the role of aspirin after bypass procedures.

Effect of Long Term Prediagnostic Aspirin Intake on the Prognosis of Esophageal Squamous Cell Carcinoma Receiving Radical Surgery

Background:The effect of long term prediagnostic aspirin intake on the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. We aimed to reveal the effect of long term prediagnostic aspirin intake on survival of ESCC patients receiving radical surgery. Methods:147 eligible ESCC patients who received radical surgery for primary treatment were enrolled in this study. Patients who had used aspirin regularly for more than 3 months before diagnose were classified as aspirin group and patients who had never used aspirin before diagnose and surgery were served as non-aspirin group. The recurrence rate, disease-free survival (DFS) and overall survival (OS) were compared between the two groups to verify the effect of aspirin. Results:Patients were clarified into aspirin group (n=57) and non-aspirin group (n=90). The DFS and OS were both significantly shorter in aspirin group than non-aspirin group (DFS: 23.1±18.0 months vs. 30.9±19.8 months, P=0.018; OS: 29.8±17.4 months vs. 35.2±18.2 months, P=0.082). Survival analysis revealed that OS decreased in aspirin group than in non-aspirin group, however, it did not reach significance (P=0.074). DFS decreased significantly in aspirin group than non-aspirin group in both univariate (P=0.007) and multivariate (P=0.002) survival analysis. Subgroup analysis revealed that in pTNM stage 2, OS and DFS were reduced in non-aspirin group compared with aspirin group (P=0.048 and P=0.003, respectively), while no difference was found in stage 3.Conclusions:Long term prediagnostic aspirin intake may cause poor DFS in ESCC patients receiving radical surgery, especially for those in pTNM stage 2.

The Protective Effect of Aspirin against Myocardial Hypertrophy in Rats

The protective effect of aspirin against myocardial hypertrophy (MH) was studied. Model rats of pressure overload MH were prepared by abdominal aortic coarctation. Rats were randomly divided into the sham group ( n = 9 ), MH model group ( n = 9 ), and MH+aspirin group ( n = 9 ), which was, respectively, divided into the 4-week group and 8-week group according to the time of intragastric administration. Arterial blood pressure and left ventricular mass index (LVMI) were measured. Changes in myocardial tissue structure were observed by HE staining, Masson staining, and reticular fiber staining. Cardiomyocyte apoptosis was detected by TUNEL assay. The levels of TNF-α, IL-10, TXA2, and PGI2 in myocardium and plasma were detected by ELISA. The arterial blood pressure in the MH model group was significantly higher than that in the 4- and 8-week sham groups, but that in the MH+aspirin group was significantly lower than that in the MH model group. At 4 and 8 weeks, the LVWI in the MH model group was significantly higher than that in the sham group, but it was significantly reduced after aspirin treatment. The myocardial cell hypertrophy was obvious, collagen fibers were proliferated, and reticular fibers were reduced in the 4- and 8-week MH model groups. Compared with the MH model groups, myocardial cells in the MH+aspirin groups were significantly reduced, the collagen fiber content was significantly reduced, and the reticular fiber content was increased. The apoptotic cardiomyocytes in the 4- and 8-week MH model groups were obviously increased. The apoptosis of myocardial cells in the MH+aspirin groups was obviously decreased. The TNF-α levels in the myocardial tissue of the 4- and 8-week MH model groups were significantly increased, while those of the MH+aspirin groups were significantly decreased. There was no significant change in the IL-10 level or PGI2 level at 4 weeks. At 8 weeks, the PGI2 level was significantly decreased in the MH model group while significantly increased in the MH+aspirin group. The TXA2 levels were significantly increased in the 4- and 8-week MH model groups and those in the 4- and 8-week MH+aspirin groups were significantly lower. Aspirin has an anti-inflammatory effect, can effectively reduce the expression of inflammatory factors, inhibit myocardial apoptosis, and has a certain protective effect against MH.

Therapeutic effect of yinchenhao decoction on cholelithiasis via mucin from gallbladder-intestine

Background: Cholelithiasis, known as gallstone, was a common and frequently occurring disease worldwide. Mucus was a viscoelastic protective layer lining the surface of mucosa and synthesized by specialized epithelial cells. Yinchenhao decoction was a classic prescription, first documented in Treatise on Febrile Disease. It had a definite and significant therapeutic effect on cholelithiasis, used as a complement to surgery. Our study aimed to investigate the pathological mechanism of cholelithiasis and the therapeutic mechanism of yinchenhao decoction via mucin from gallbladder-intestine.Methods: The solubility of cholesterol in fasted state simulated intestinal fluid (FaSSIF) without and with mucin was tested. The experiment of supersaturation stability was designed by solvent-shift method. The animal experiment was performed by cholelithiasis model of high cholesterol diet. The stones were observed and the related lipid was tested by automatic biochemical analyzer. The mucin was detected by PCR and western blot. Statistics was analyzed using χ2-tests and t-tests.Results: There was no significant difference in the solubility of cholesterol between FaSSIF without and with mucin. Tss or AUC significantly increased with addition of mucin to FaSSIF (p<0.05). A significant difference was observed in stone rate between the normal group and the model group (p<0.05). Stone rate in the model group showed a significant difference from the yinchenhao decoction group (aspirin group) (p<0.05). The level of related lipid showed a significant increase between the normal group and the model group (p<0.05), while there was a significant decrease between the model group and the yinchenhao decoction group (aspirin group) (p<0.05). A significant increase in the MUC5AC or MUC2 expression was observed between the normal group and the model group (p<0.01). The yinchenhao decoction group (aspirin group) caused a significant decrease in the MUC5AC or MUC2 expression, compared with the model group (p<0.01).Conclusions: In cholelithiasis, the mucin in gallbladder (MUC5AC) highly expressed, shortened cholesterol supersaturation, and promoted cholesterol crystallization; the mucin in small intestine (MUC2) highly expressed, prolonged cholesterol supersaturation, and promoted cholesterol absorption. The yinchenhao decoction inhibited the expression of mucin from gallbladder-intestine for the treatment of cholelithiasis.