Aspirin Research Articles

The cardiovascular polypill strategy (acetyl salicylic acid, atorvastatin, ramipril) as baseline treatment after a cardiovascular event supported by compelling evidence: a global expert consensus

Abstract Background The SECURE trial demonstrated that the CV-polypill strategy (acetylsalicylic acid [ASA]+atorvastatin+ramipril) reduces CV mortality by 33% in patients with acute myocardial infarction (MI) compared to standard care over 3 years (median). The 2023 ACS ESC Guidelines recommend the polypill strategy to improve outcomes and treatment adherence. The CV-polypill inclusion in the 2023 World Health Organization's essential medicines list signifies its effective and affordable response to a global secondary prevention healthcare requirement. Purpose To reach consensus among medical experts from various countries regarding key implementation aspects of the CV-polypill strategy (ASA+atorvastatin+ramipril) as baseline preventive treatment after a CV event (CVe) in routine clinical practice. Methods A two-round modified Delphi method was employed. A questionnaire consisting of 30 evidence-based statements was developed and validated with input from 8 distinguished cardiologists. The Delphi panel, 50 physicians from 19 countries across Europe, Latin America, and Asia, used a three-point Likert scale to establish their agreement and perceived importance of the statements. Consensus was reached when ≥80% agreed or deemed statements 'very important' or 'important. Statements without consensus in the first round underwent refinement based on evidence and panellists’ feedback in the second round. Persistent disagreements were resolved in a face-to-face meeting with experts. Descriptive statistics were applied. Results 38/50 panellists participated in round 1, and 37/50 in round 2. 31/38 were cardiologists. 28/38 routinely prescribed the CV-polypill strategy. 97.4% of panellists believed that the 24% relative risk reduction in major CVe over 3 years (median), attained with the CV-polypill strategy (ASA+atorvastatin+ramipril) compared to standard care could replicate in clinical practice while maintaining equal safety (97.4%). Unanimous consensus (100%) supported initiating the CV-polypill strategy as baseline preventive treatment upon hospital discharge or at first follow-up. Its efficacy and safety were also acknowledged for stroke (94.7%), peripheral artery disease (92.1%), and both genders (84.2%). 89.5% supported CV-polypill affordability for preventing CHD events and strokes. Algorithms for initiation (97.3%) and transition (97.4%) to the CV-polypill strategy from cardioprotective drugs, considering patient preferences (97.5%), were confirmed. A unanimous consensus (100%) affirmed the positive impact of the simplified CV-polypill treatment on patient satisfaction, with 94.7% recognizing its convenience (Figure 1). Conclusions Skilled medical experts across continents reached consensus on critical implementation aspects and strongly endorse the early use of the CV-polypill strategy (ASA+atorvastatin+ramipril). This adoption aims to reduce CVD recurrence, improve prognosis, and potentially enhance affordability in CVD treatment after a CVe.Consensus on CV polypill implementation

Patients with dementia: prevalence and type of drug–drug interactions

BackgroundPatients with Alzheimer’s disease (AD) and other dementias are more frequently exposed to polymedication, mainly due to the presence of comorbidities, are particularly vulnerable to drug-related problems, and present greater risk of adverse effects due to drug–drug interactions (DDIs).PurposeTo assess the prevalence of clinically relevant interactions in dementia patients using a routine database, we describe the most frequent interactions and risk factors associated with them to facilitate specific interventions and programs to prevent and minimize them.MethodsAn observational, descriptive, and cross-sectional study that included patients with AD and other types of dementia (n = 100, 64% female) was conducted to identify potential DDI in their treatment using the Lexi-Interact/Lexicomp® database.ResultsA total of 769 drugs were prescribed, involving 190 different active ingredients; 83% of the treatments included five or more drugs. DDI occurred in 87% of the patients, of which 63.2% were female. A total of 689 DDIs were found, grouped in 448 drug pairs, with a mean of 6.9 ± 7.1 (range, 0–31) DDIs per patient, and 680 DDIs were considered clinically relevant. It was observed that 89.8% of the DDIs had a moderate level of severity, 23.5% had a good level of relevance, and pharmacodynamic-based DDIs accounted for 89.5%. The drugs most frequently involved in DDIs were quetiapine (24.5%) and acetylsalicylic acid (10%). A total of 97 DDIs were detected between the acetylcholinesterase inhibitors (AChEIs), and the remaining drugs were administered concomitantly. One of the most frequent DDIs was between AChEIs and beta-blocking agents (n = 29, 4.3%). The most important factors that showed the strongest association with the presence of drug interactions were the use of AChEIs (p = 0.01) and the total number of drugs (p = 0.014) taken by the patient.ConclusionPatients with dementia present increased risk of DDIs. Among the most common drugs are psychotropic drugs, which are involved in pharmacodynamic interactions caused by the concomitant use of CNS-targeted drugs. The results highlight the difficulty to evaluate DDIs in clinical practice due to polymedication and variety of comorbidities. Therefore, it is important to review their treatment and consider metabolism inhibition or induction, and potentially P450 substrate overlapping.

Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry

Abstract Introduction Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials. Purpose To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF. Methods The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest. Results Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF >40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of > 40%. Conclusion In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status

A DIFFERENT VIEW OF MINOCA; A RARE CASE OF CORONARY CAMERAL FISTULA

Abstract Coronary cameral fistula (CCF) is defined as an abnormal connection between the coronary artery and the heart chambers. Although rare, most are asymptomatic, usually arising from the right coronary artery and terminating in the right ventricle or right atrium. Often detected incidentally, CCFs may present with symptoms of heart failure or rarely with anginal symptoms. Introduction A coronary cameral fistula is defined as an abnormal connection between the coronary artery and the heart chambers. CCFs are found in less than 1% of the population.[1] The most common coronary artery fistula is that arising from the right coronary artery and spilling into the right ventricle.[2] In particular, CCFs arising from all three epicardial coronary arteries are rare but can be clinically significant. These cases may present with acute coronary syndrome causing steal syndrome. Since there is usually no underlying obstructive lesion, these cases may be diagnosed as myocardial infarction without obstructive coronary arteries (MINOCA)[3] Case; A 51 years old male patient was admitted to the emergency room with a complaint of stabbing chest pain for the last one week. In his anamnesis, he described that the chest pain increased with exertion and radiated to the back. It was learned that he had no known disease and coronary history, was a 20 pack/year smoker, had no family history and was not taking any medication regularly. Vital signs in the emergency room revealed a blood pressure of 120/80 mmHg, pulse rate of 85 per minute and normal saturation. Electrocardiography (ECG) showed sinus rhythm V 1-6 with T negativity 85/min. (Figure 1) Echocardiography revealed no wall motion defect and no major valve pathology. Laboratory findings showed renal function tests within normal range, C-reactive protein within normal range, hemoglobulin level 17.6 gr/dl, HS Troponin-T level 12.9 ng/l (upper limit 14 ng/l). At 3 hours, the control HS Troponin-T level was 69.2 ng/l and the patient was hospitalized in the coronary intensive care unit with a prediagnosis of acute coronary syndrome. Coronary angiography was performed during follow-up. Angiography showed dilatation in the main coronary artery (LMCA), ectasia in the left anterior descending artery (LAD) and circumflex artery (CX), and diffuse tortuosity in the coronaries. CCF formed by the LAD, CX and right coronary artery (RCA) together and spilled into the left ventricle. Opaque filling was observed in the left ventricle. (Figure 2) Although the patient had a low body mass index, dilatation of the coronary arteries was thought to be the effect of steal syndrome caused by multiple fistulas. The patient was admitted to the coronary intensive care unit with medical follow-up. The patient's medical treatment was adjusted as acetylsalicylic acid (ASA) 100 mg pill 1*1, metaprolol 50 mg pill 1*1 and rosuvastatin 20 mg pill 1*1 due to an LDL cholesterol level of 149 mg/dl. In the patient who currently had no signs of heart failure, medical treatment was decided primarily in terms of CCF. The patient was discharged with the recommendation of outpatient follow-up. Discussion and Conclusion; CCFs are rare coronary anomalies.[1] When we look at the etiology, the most common cause of CCFs is abnormal embryogenesis.[4] While the diagnosis can be made at any age, the diagnosis is usually made in early childhood when a heart murmur occurs in an asymptomatic child or in a child with symptoms of heart failure. However, cases of CCF diagnosed at an advanced age with anginal complaints and signs of acute heart failure are seen in the literature. [5]Treatment depends on the anatomical features of the fistula and, of course, the patient's symptoms. While small fistulas may close spontaneously with age, large fistulas may require closure.It may cause anginal symptoms by causing heart failure symptoms and steal syndrome. [6]When we look at the literature, we can see that patients with CCF also present with acute coronary syndrome. [2, 4, 5,] As in the case reported by Alsancak Y et al., CCFs originating from all three coronary arteries cause steal syndrome and are often diagnosed with a prediagnosis of acute coronary syndrome.[7] The absence of an occlusive lesion after angiography in these patients with high troponin levels suggests atherosclerosis at the microvascular level and the diagnosis of MINOCA. [3]Angiography performed with suspicion of stenosis in the coronary arteries and finding a CHF instead of a stenosis may be considered lucky in these patients. The size of the fistula and the possibility that it may lead to heart failure in the follow-up will be the other side of the unlucky coin.

Acetylsalicylic acid dosed at bedtime vs. dosed in the morning for circadian rhythm of blood pressure- a systematic review and meta-analysis

IntroductionCardiovascular disease (CVD) is a leading global cause of morbidity and mortality, with high systolic blood pressure (SBP) identified as a major risk factor. Aspirin (Acetylsalicylic acid—ASA) has been considered for CVD prevention, prompting questions about its optimal use in primary and secondary prevention and the ideal dosing time to maximize its impact on circadian blood pressure rhythms. Previous research suggests a potential benefit of bedtime aspirin dosing in reducing blood pressure, attributed to its effects on the renin-angiotensin-aldosterone system and nitric oxide production. This systematic review and meta-analysis aim to further explore the circadian effects of aspirin on blood pressure, focusing on the timing of administration.MethodsAdhering to PRISMA guidelines, a comprehensive search of PubMed, Cochrane Library, and clinicaltrials.gov was conducted. Randomized controlled trials (RCTs) involving patients aged >18 with cardiovascular history and hypertension were included. The primary objective was to assess the impact of bedtime-dosed and morning-dosed aspirin on systolic and diastolic blood pressure. Low-dose aspirin was administered for primary or secondary prevention. The Cochrane Risk of Bias tool evaluated study quality. Meta-analyses were conducted using RevMan 5.3, with mean deviations and 95% confidence intervals employed for outcomes.ResultsInitial searches yielded 1,181 articles, with six studies meeting the inclusion criteria. These RCTs involved 1,470 patients, with 1,086 completing follow-up. Bedtime aspirin dosing demonstrated a significant reduction in both systolic and diastolic blood pressure compared to morning dosing (p < 0.05). Meta-analysis results for systolic blood pressure revealed a weighted mean difference of approximately 3.65 mmHg in favour of bedtime dosing, with low heterogeneity (I2 = 0%). For diastolic blood pressure, the weighted mean difference was 1.92, again favouring bedtime dosing, with 3% heterogeneity.ConclusionThis meta-analysis, involving over 1,300 cardiovascular/hypertensive patients, supports the effectiveness of bedtime aspirin in reducing systolic and diastolic blood pressure compared to morning dosing. The results align with previous findings but distinguish themselves by incorporating a more diverse patient population and addressing moderate heterogeneity. While the study's outcomes are promising, further research, including larger sample sizes and longer durations, is warranted for comprehensive clinical implementation. As the study exclusively focused on aspirin timing, future investigations should explore sustained blood pressure effects in patients with clinical indications for aspirin alongside other hypertensive medications.

Characteristics of COVID-19-associated multisystemic inflammatory syndrome in children treated in a Peruvian hospital, 2020-2022.

Motivation for the study. There are few studies describing the variation of COVID-19-associated multisystem inflammatory syndrome (MIS-C) in Peru across pandemic waves. Main findings. Cases of MIS-C decreased during the first three years of the pandemic, with higher frequency in the second wave with clinical features similar to Kawasaki disease. Implications. MIS-C is a post-infectious complication of SARS-CoV-2. Its diagnostic suspicion is important weeks after peak infections, especially in children who have not yet received COVID-19 vaccines. This study aimed to describe the characteristics of multisystemic inflammatory syndrome associated with COVID-19 (MIS-C) in the first three years of the pandemic in children in a pediatric hospital in Peru. We conducted an observational, descriptive study with data from 73 patients and described the clinical and laboratory characteristics, treatment and complications according to the wave of the pandemic and whether they had shock. The median age was 6 years, gastrointestinal and mucocutaneous manifestations were frequent in the three waves. Kawasaki disease-like phenotype was present in 34 (46.6%) patients and 21 (28.8%) patients developed shock. The most commonly used treatment was immunoglobulin (95.9%), followed by acetylsalicylic acid (94.5%) and corticosteroid (86.3%). Five (7%) patients had coronary aneurysm and 17 (23.3%) were admitted to the intensive care unit (ICU). Patients with shock had greater laboratorial alteration and need for mechanical ventilation. In conclusion, MIS-C has decreased in the first three years of the pandemic, possibly due to COVID-19 vaccination in children.

Adverse Pregnancy Outcomes and Chronic Hypertension in the Era of Prevention: A Contemporary, Retrospective Cohort Study Using Data from the National Inpatient Sample Database.

Chronic hypertension is a known risk factor for the development of preeclampsia and obstetrical morbidity. However, recent risk estimates, particularly in the era of use of low-dose acetylsalicylic acid for preeclampsia prevention, are lacking. This study aimed to estimate the association between chronic hypertension and preeclampsia and other adverse pregnancy outcomes in a contemporary cohort of births spanning the period, since the introduction of a low-dose acetylsalicylic acid protocol. The secondary outcome was to estimate trends in preeclampsia and preterm birth among patients with chronic hypertension during the study period. A retrospective, population-based cohort study was conducted using the National Inpatient Sample Database to identify individuals discharged from hospitals in the United States following obstetrical delivery from 2014 to 2019. Pregnancies complicated by chronic hypertension were identified using ICD 9/10 (International Classification of Diseases 9th and 10th editions) codes. Multivariable logistic regression models were used to estimate the adjusted odds ratios for the association between chronic hypertension and adverse pregnancy outcomes compared with pregnancies not complicated by chronic hypertension. Temporal trends in preeclampsia and preterm birth among patients with chronic hypertension were estimated over the study period. Among 4,451,667 obstetrical delivery-related admissions, 139,556 (3.1%) included pregnancies complicated by chronic hypertension. Of these, 27,146 (19.4%) admissions included pregnancies with superimposed preeclampsia, compared with 222,351 (5.2%) of admissions that included pregnancies with preeclampsia without prior diagnosis of chronic hypertension. Pregnancies complicated by chronic hypertension were associated with 3.29 times the odds of preeclampsia compared with pregnancies without chronic hypertension (95% confidence interval: 3.22-3.36), but the odds of preeclampsia (p-value for linear trend <0.0001) and preterm birth (p-value for linear trend = 0.0001) in this subgroup decreased over the study period. While the odds of preeclampsia are increased among pregnancies complicated by chronic hypertension, the odds of preeclampsia in this population have decreased over time. · Pregnancies complicated by chronic hypertension are at significantly higher odds of preeclampsia.. · Recent guidelines have recommended low-dose acetylsalicylic acid for preeclampsia prevention in these pregnancies.. · In a nationwide cohort, the odds of preeclampsia among these pregnancies are decreasing over time..

Aspirin Hypersensitivity in Patients with Coronary Artery Disease: An Updated Review and Practical Recommendations.

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity.

Metabolic characteristics of ischaemic preconditioning induced performance improvement in Taekwondo athletes using LC‒MS/MS-based plasma metabolomics.

In recent years, ischemic preconditioning (IPC) has garnered significant attention in sports research. While IPC has demonstrated positive effects in high-intensity sports such as judo and swimming, its potential benefits for enhancing the performance of Taekwondo athletes have not been extensively studied. This study aimed to investigate the effects of IPC on taekwondo performance and to observe the metabolic characteristics associated with enhancing sports performance via LC‒MS/MS-based plasma metabolomics. Seventeen participants underwent the repeated frequency speed of kick test (FSKT) after IPC, along with pre- and post-exercise plasma metabolite analysis. Differential abundance metabolite analysis, enriched pathway analysis, and weighted gene coexpression network analysis (WGNCA) were employed to delve into metabolic characteristics. The findings highlighted a significant enhancement in FSKT performance in the experimental group. Metabolomic analysis revealed 109 differentially abundant metabolites, including Dl-lactate, hypoxanthine, acetylcarnitine, and acetylsalicylic acid. Enriched pathway analysis revealed pathways such as pentose and glucuronic acid interconversion, ascorbic acid and aldonic acid metabolism, the pentose phosphate pathway (PPP), and the Warburg effect. In conclusion, IPC can significantly increase the specific athletic abilities of Taekwondo athletes, with enhancements linked to anaerobic metabolism, PPP utilization, the Warburg effect for energy production, redox system stability, reduced muscle fatigue, and pain alleviation.

Biological Activity Evaluation of Phenolic Isatin-3-Hydrazones Containing a Quaternary Ammonium Center of Various Structures.

A series of new isatin-3-hydrazones bearing different ammonium fragments was synthesized by a simple and easy work-up reaction of Girard's reagents analogs with 1-(3,5-di-tert-butyl-4-hydroxybenzyl)isatin. All derivatives have been shown to have antioxidant properties. In terms of bactericidal activity against gram-positive bacteria, including methicillin-resistant strains of Staphylococcus aureus, the best compounds are 3a, 3e, and 3m, bearing octyl, acetal, and brucine ammonium centers, respectively. In addition, brucine and quinine derivatives 3l, and 3j exhibit platelet antiaggregation activity at the level of acetylsalicylic acid, and this series of isatin derivatives does not adversely affect the hemostasis system as a whole. Thus, all the obtained results can lay the groundwork for future pharmaceutical developments for the creation of effective antibacterial drugs with reduced systemic toxicity due to the presence of antioxidant properties.

Platelet Function, Platelet Size and Content of Reticulated Platelets: Interactions in Patients Receiving Dual Antiplatelet Therapy.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy.

Drug-drug-interactions in patients with atrial fibrillation admitted to the emergency department

IntroductionPolypharmacy is a growing concern in healthcare systems. While available data on potential drug-drug interactions (pDDI) from emergency department (ED) patients is derived from heterogenous populations, this study specifically focused on patients with atrial fibrillation (AF). We hypothesized that patients with AF have similar comorbidities, receive similar drugs, and have similar pDDIs. The overarching aim was to highlight frequent pDDIs, providing practical guidance for treating healthcare professionals and consequently reduce the risk of adverse drug reactions.MethodsTwo hundred patients ≥18 years with AF, who received rate- or rhythm-controlling medication at the ED of the University Hospital Vienna, and who were on long-term medication before admission, were eligible. Long-term medication alone, as well as in combination with medication administered at the ED were analyzed for pDDIs using the Lexicomp® Drug interactions database.ResultsWithin the long-term medication of patients’, we identified 664 pDDIs. Drugs administered at the ED increased pDDIs more than 3-fold to 2085. Approximately, every fifth patient received a contraindicated drug combination (on average 0.24 per patient), while 70% received drug combinations for which therapy modifications are recommended (on average 1.59 per patient). The most frequently involved drugs included amiodarone, propofol, bisoprolol, enoxaparin, and acetylsalicylic acid. Increased risk of bleeding, QTc prolongation, and myopathy were among the most relevant potential consequences of these interactions.DiscussionIn conclusion, an optimization of medication would be advisable in almost every AF patient. Treating healthcare professionals should be cautious of drugs that increase bleeding risk, prolong QTc, or bear a risk for myopathy.

Acute toxicity and anti-inflammatory activity of an improved traditional medicine developed in Burkina Faso

An Improved Traditional Medicine (ITM) in capsule form presented by traditional health practitioners in Burkina Faso as used for hepatoprotective and hepatocurative treatment for viral hepatitis B. The study's main objective was to investigate the anti-inflammatory properties of this ITM, which is used in treating viral hepatitis B in traditional medicine in Burkina Faso. Phytochemical screening revealed the presence of flavonoids, saponins, tannins, coumarins, alkaloids, sterols and triterpenes. The in vitro anti-inflammatory assay inhibited LOX by 15.69 ± 0.50% at a 100 µg/mL concentration. The LD50 was estimated to be greater than 5000 mg/kg. In vivo activity using the carrageenan anti-oedema test showed good dose-dependent anti-inflammatory activity of ITM at 30, 65 and 130 mg/kg bw. After 3 hours, the extract at various doses reduced edema to over 50% inhibition. After 5 h, oedema was reduced to 85.209% at the 130 mg/kg. However, the reference acetylsalicylic acid (ASA) at 100 mg/kg bw showed a percentage of 85.048% at 5 h. The IC50 obtained after the ABTS, FRAP and LPO antioxidant tests of the phytomedicine were 351.00 µg/mL, 353.20 mM EAA/L and 81.13%. However, the IC50 with the DPPH method was higher than 104 mg/mL. The phytomedicine would have anti-inflammatory and antioxidant properties due to the presence of bioactive phytochemicals on inflammation and free radicals. Keywords: ITM, Phytochemical, Acute toxicity, Anti-inflammatory, Antioxidants

Harmony in Healing: Investigating Platelet-Rich Plasma Activation during Acetylsalicylic Acid Treatment

Platelet-rich plasma (PRP) therapy holds promise for treating various clinical conditions. The activation process is crucial in releasing growth factors and cytokines from platelets, enhancing the therapeutic properties of PRP. Standard activation methods involve autologous thrombin or collagen, with variations in efficacy and growth factor release. This study explores the impact of acetylsalicylic acid (ASA), a commonly used antiplatelet drug, on PRP activation. The results indicate that non-activated PRP extracted from the whole blood of ASA-treated patients exhibits increased inflammatory cytokine concentrations, notably TNFa. After activation with autologous thrombin/CaCl2 or collagen IV, the measured fluorescence intensities suggest varying release patterns between treated and non-treated groups. Understanding the influence of ASA on platelet activation holds implications for personalized medicine and optimizing outcomes for individual patients undergoing PRP therapy. This research sheds light on the potential challenges associated with using antiplatelet drugs, emphasizing the need for careful consideration in tailoring PRP-based regenerative therapies.

The trajectory of serum salicylate concentrations after ingestion of medicinal oil containing methyl salicylate

Introduction The toxicokinetics of methyl salicylate after unintentional or intentional ingestion of medicinal oil containing methyl salicylate has not been well studied. We aimed to characterize the trajectory of serum salicylate concentrations and to evaluate factors associated with the peak serum salicylate concentration and the time from ingestion to peak concentration. Methods This was a retrospective cohort study of consecutive patients reported to the Hong Kong Poison Control Centre for laboratory-confirmed methyl salicylate poisoning by all local public emergency departments between 1 July 2008 and 30 June 2023. We analyzed cases with at least three serum salicylate concentrations. Multivariable generalized linear regression was used to identify factors significantly associated with the peak serum concentration and the time from ingestion to peak concentration. Results We included 41 patients (median age 81.0 years; 32 women and nine men). The median time from ingestion to the first peak serum salicylate concentration was 5.6 h (IQR: 3.2–10.8 h). Multiple regression showed that gastric aspiration (adjusted regression coefficient [β] − 2.50; 95% CI: −3.93 to −1.08; P = 0.001) and single-dose activated charcoal (adjusted β − 1.22; 95% CI: −2.02 to −0.42; P = 0.003) were significantly associated with a lower peak concentration, after adjusting for patient age, sex, exposure due to intentional self-harm, reported ingested dose, time from ingestion to emergency department presentation, vomiting, concurrent use of aspirin (acetylsalicylic acid) and other medications that affect gastric emptying or gastric acid secretion, blood pH, serum albumin concentration, and creatinine clearance. Discussion The serum salicylate concentration did not peak as quickly as generally believed, highlighting the importance of continued monitoring. Gastric aspiration and single-dose activated charcoal may help reduce gastrointestinal absorption, but their impact on clinical outcomes remains unclear. Conclusions Given the median time of 5.6 h (IQR: 3.2–10.8 h) from ingestion to the peak salicylate concentration, gastric aspiration and single-dose activated charcoal can be considered in patients up to a few hours after medicinal oil ingestion when the airway is protected.

125 Years of Aspirin: Status of Analytical Methods.

Aspirin, an analgesic, antipyretic and non-steroidal anti-inflammatory drug, was a fascinating discovery that became the precursor to one of the oldest pharmaceutical success stories. It was discovered in 1899 by Felix Hoffman and patented in 1900. In 2024, Aspirin turns 125 years old and is still one of the bestselling medicines today. This review aims to celebrate 125 years of Aspirin and show the status of analytical methods available in the literature to evaluate pharmaceutical products based on Acetylsalicylic Acid (ASA). In addition, it contextualizes them with the current needs of green and clean analytical chemistry. ASA, despite being consolidated in the consumer market, embraces continuous improvement as it is a fundamental part of studies for other new purposes and studies with associations with other active ingredients. In the manuscripts available in the literature, ASA is predominantly evaluated by HPLC (41%) and UV-Vis (41%) methods, which use methanol (21.82%) and acetonitrile (18.18%), followed by buffer (16.36%). The most evaluated pharmaceutical matrix is ASA tablets (40%), followed by ASA tablets in combination with other drugs (26%). While ASA continues to innovate in the market through new forms of delivery and combinations, as well as intended purposes, the analytical methods for evaluating its pharmaceutical products do not. They continue with non-eco-efficient analytical options, which can significantly improve and meet the current demand for green and sustainable analytical chemistry.

Dynamic monitoring of the endothelium function in pregnant women at high risk of preeclampsia during pathogenetic prevention of its development

BACKGROUND: Today, preclinical diagnosis of preeclampsia presents significant difficulties. In widespread practice, it is diagnosed based on existing clinical signs and laboratory and functional research methods. Most of them are invasive and expensive, which makes it difficult to use them in widespread clinical practice for diagnosis and, especially, for monitoring the effectiveness of therapy over the dynamics of the disease. It is known that the pathogenesis of preeclampsia can have two independent development paths, converging in a common resulting link — the formation of endothelial dysfunction. Methods for studying endothelial function include determining markers of its imbalance in blood samples and non-invasive functional tests. Non-invasive diagnosis of endothelial dysfunction using the EndoPAT test allows us to quantify endothelium-mediated changes in vascular tone during 5-minute occlusion of the brachial artery. AIM: The aim of this study was to evaluate the method for determining the endothelium function in the first, second and third trimesters of pregnancy during ongoing pathogenetic prevention of preeclampsia. MATERIALS AND METHODS: This interventional uncontrolled study of the effectiveness of preventing preeclampsia using non-invasive assessment of vascular endothelial dysfunction during pregnancy was conducted at the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, St. Petersburg, Russia. The study involved 108 pregnant women at high risk of developing preeclampsia. All pregnant women underwent a cuff test to determine endothelial dysfunction using the peripheral arterial tonometry technique on the Endo-PAT 2000 device. The dynamic study was carried out in the first, second and third trimesters of pregnancy. As a result of the study, when endothelial dysfunction was detected [logarithmic transformation of reactive hyperemia peripheral arterial tonometry index (LnRHI) less 0.51], a complex glycosaminoglycan was additionally added to the basic prophylaxis with acetylsalicylic acid at a dosage of 250 MU (one capsule three times a day for eight weeks), then a cuff test was monitored after 6–12 weeks. Statistical analysis was performed using the IBM SPSS Statistics 20 software. All tests for significance were two-tailed, and differences were considered significant at p 0.05. RESULTS: Endothelial dysfunction was detected in the first trimester in 59 (55%) patients, then during ongoing complex therapy in the second trimester (n = 72) in 46 (64%) patients and in the third trimester (n = 46) in 4 (1%) patients. Moderate preeclampsia in the third trimester (35–39 weeks of gestation) developed in 28 (25.9%) patients out of 108. At the same time, at the start of the study, 15 patients with endothelial dysfunction received complex therapy, and 13 individuals only took acetylsalicylic acid. Among 46 patients who observed the dynamics of the entire pregnancy, only 4 (8.7%) women developed preeclampsia. After complex treatment prescribed based on the first trimester parameters, out of 36 patients who discontinued complex therapy and did not undergo a functional test subsequently, preeclampsia developed in 16 (44.4%) women. In the second trimester, out of 26 patients who stopped complex therapy, preeclampsia developed in 8 (30.8%) people. Thus, constant monitoring and complex therapy reduced the frequency of preeclampsia. In the group with a history of preeclampsia, the disease developed in 13 (39.4%) women. In the group with a high risk of preeclampsia according to the results of combined prenatal screening in the first trimester, with the exception of a history of preeclampsia (blood pressure test, placental growth factor level in the blood serum, lowest uterine artery pulsatility index value calculated to assess the individual risk of preeclampsia with a titer less than 1 : 100), preeclampsia occurred in 4 (13.3%) women. In the group with extragenital pathology associated with the risk of preeclampsia, including obesity, pregestational diabetes mellitus, chronic arterial hypertension, and chronic kidney disease, with the exception of a history of preeclampsia and a high risk of preeclampsia according to the results of perinatal screening, preeclampsia occurred in 11 (24.4%) women. In the high–risk groups for preeclampsia, we identified the highest-risk group, namely, one with the presence of preeclampsia in the anamnesis. CONCLUSIONS: The effectiveness of the functional method for determining endothelial dysfunction in the first, second and third trimesters of pregnancy during pathogenetic prevention of preeclampsia has been proven.

Base-Catalyzed Reaction of Isatins and (3-Hydroxyprop-1-yn-1-yl)phosphonates as a Tool for the Synthesis of Spiro-1,3-dioxolane Oxindoles with Anticancer and Anti-Platelet Properties

An approach to the synthesis of phosphoryl substituted spiro-1,3-dioxolane oxindoles was developed from the base-catalyzed reaction of various isatins with (3-hydroxyprop-1-yn-1-yl)phosphonates. It was found that various aryl-substituted and N-functionalized isatins with the formation of appropriate products with high yields and stereoselectivity when using t-BuOLi are able to react. Cytotoxic activity evaluation suggests that the most significant results in relation to the HuTu 80 cell line were shown by N-benzylated spirodioxolanes. 5-Cloro-N-unsubstituted spirooxindoles exhibit antiaggregational activity exceeding the values of acetylsalicylic acid.

Assessment of IV albumin and ringer lactate on the acute oral toxicity of acetylsalicylic acid in albino rats

BackgroundDespite the frequent inclusion of fluid therapy in the treatment of many conditions, there are limited studies available to provide an evidence-based specific recommendation for fluid therapy in acute drug toxicity. Salicylate toxicity is considered one of the common clinical problems. It is commonly associated with fatal complications and even can lead to death. The study was designed to investigate the effects of various IV fluid types as isotonic saline (NaCl 0.9%), Ringer lactate (RL), and albumin and their impact on acetyl salicylic acid (ASA) toxicity outcome in a rat model of acute salicylate toxicity.Sixty male Albino rats were divided into 10 groups of 6 rats each. The first four groups were the control, saline, RL, and albumin groups. The fifth group received two doses of ASA solution orally, and the next five groups were treated with IV fluids as follows: saline-ASA, RL-ASA, albumin-ASA, RL + albumin-ASA, and saline + albumin-ASA. Upon completion of the study, spirometry, arterial blood gas analysis (ABG), and serum liver and kidney function tests were done on all groups. Furthermore, quantitative real-time polymerase chain reaction (PCR) was used to assess interleukin-6 (IL6), nuclear factor kappa beta (NF-kβ), and beta-actin mRNA gene expression of histopathology and immunohistochemistry assessments were also performed on liver and kidney tissues.ResultsThe results revealed the ASA group showed marked deterioration across all the investigated parameters. The groups that received saline and RL showed improvements in the following: respiratory rates, ABG, liver and kidney function, and histopathological findings.The RL + albumin group did not show any improvements. The albumin group and the saline + albumin group showed variable responses, ranging from mild improvement to no improvement.ConclusionsThe saline and RL groups showed positive results; however, the RL + albumin group showed the worst outcomes. The inclusion of albumin did not appear to provide any extra benefits and produced varying results.

Scandinavian Neurotrauma Guidelines: Frequency of intracranial hemorrhage in patients over 65 years old and on anti-platelet medication

PurposeIn 2013, the Scandinavian Neurotrauma Committee, produced an evidence-based guideline for the use of Computed Tomography (CT) in patients presenting following recent (<24 h) head injury (HI). A head CT scan is recommended for medium-risk patients with a Glasgow Coma Scale (GCS) score of 14–15, who are > 65 years old and on anti-platelet medication. The aim of this study was to determine the prevalence of intracranial hemorrhage (ICH) on head CT scans in this population, and to test for associations between ICH and baseline characteristics, symptoms and objective clinical findings. MethodsThis register-based retrospective study determined the prevalence of ICH on head CT scans performed over a 1-year period based on written CT-reports. Patient medical charts and imaging records were examined for data on symptomatology, objective findings and comorbidities. ResultsThe study population included 325 unique head CT scans with a 5.2% prevalence of ICH. Risk ratios (RR’s) signified higher risk of ICH with a GCS score of 14 compared to a GCS score of 15 (RR 5.35, 95%CI 2.14–13.47). ICH risk was lower in patients on Clopidogrel medication compared to Acetylsalicylic Acid medication (RR 0.33, 95%CI 0.12–0.93). ConclusionsThe associations between ICH and the GCS score call attention to the importance of comprehensive clinical examination of HI patients to minimize CT overuse. The implications for patients and healthcare resources in scanning patients > 65 years on anti-platelet medication should be determined by future prospective studies.