High-dose Acetylsalicylic Acid Research Articles

Acetylsalicylic acid as the only pharmacological method for the prevention of preeclampsia: A retrospective study

Background. Preeclampsia (PE) complicates 28% of pregnancies worldwide, negatively impacting the pregnant woman and the fetus. Therefore, its prevention remains relevant. It is believed that the cause of PE, especially early PE, is a placentation disorder. It warrants studying drugs that can improve placenta development. The leadership in this matter is maintained by acetylsalicylic acid, which, according to the ASPRE study, reduced the incidence of PE at 34 weeks of pregnancy by 82%. The use of low molecular weight heparins (LMWH), dipyridamole, and antioxidants for PE prevention remains controversial and continues to be studied by foreign and Russian scientists.
 Aim. To assess the efficacy of acetylsalicylic acid, LMWH, dipyridamole (Curantyl), and bovine blood derivates (Actovegin) in the Russian population of pregnant women at high risk for PE prevention.
 Materials and methods. The study included 244 patients. We reviewed the archived case records of 103 patients diagnosed with severe PE, who delivered in 2019 at the State Clinical Hospital №24, and 141 pregnant women from the Maternity clinic №3 at the Veresaev Moscow State Clinical Hospital, where the risk of PE was assessed as high, according to the results of extended combined screening of the first trimester of pregnancy. Eighty-nine pregnant women received acetylsalicylic acid at a dose of 75 mg and 54 at a dose of 150 mg. In addition, 22 patients received LMWH, 6 dipyridamole, and 3 Actovegin. The absolute risks, the risk ratio, and statistical significance when taking drugs in each risk group were calculated to assess the efficacy of acetylsalicylic acid and other drugs for PE prevention in the above risk groups.
 Results. The resulting weak inverse correlation (r=-0.31) between the PE severity at delivery and the dose of acetylsalicylic acid indicates that an increase in the acetylsalicylic acid dose was associated with a decrease in the PE severity. The effectiveness of combinations of various drugs for PE prevention was assessed by analyzing factor correspondences. Two-dimensional scaling of the most likely combinations showed that most patients received acetylsalicylic acid in the high-risk group with no PE. Additional use of LMWH, Curantyl, and Actovegin did not reduce the risk of PE.
 Conclusion. Acetylsalicylic acid is the only pharmaceutical method for preventing PE in high-risk groups. Higher doses of acetylsalicylic acid are associated with lower PE severity.

P396 FIBRINOUS PERICARDITIS AND STILL’S DISEASE IN ADULTHOOD: A RARE AND INSIDIOUS COMBINATION

Abstract In 9/2022 we admitted a 69–year–old man with history of hypertension, in therapy with bisoprolol and edoxaban after recent diagnosis of persistent atrial fibrillation, with a minor pericardial effusion at the echocardiogram. He had dyspnea, fever, and atrial fibrillation with elevated cardiac frequency. The echocardiogram showed increased pericardial effusion, circumferential, about 2 cm, with important fibrinous organization, without signs of cardiac tamponade (fig1). Hemocultures and urocultures were repeatedly negative, with significant increase in flogosis parameters. Therapy with high–dose acetylsalicylic acid was started first and then Ibruprofene + colchicine with poor clinical response and persistence of symptoms and effusion. The presence of elevated fever, arthralgias, transient skin rush to the trunk and flogosis indices (CRP 17 mg/dl, ESR 97mm, WBC 11000/ul with 80% neutrophil, ferritin 2200 ng/ml), with negativity of antinucleus antibodies and rheumatoid factor, allowed to place diagnosis of adult Still’s disease (AOSD). High–dose steroid therapy (prednisone 1mg/kg) was initiated with fever regression, progressive normalization of inflammatory indices and spontaneous restoration of sinus rhythm. The 7–day echocardiogram showed almost complete resolution of pericardial fibrinous effusion (fig 2). At 2 months patient remained asymptomatic, no more pericardial effusion, no signs of flogosis. Differential diagnosis of pericarditis is often complex, and therapeutic attitude and prognosis are variable according to etiology. AOSD has a prevalence of about 1/100,000, affects mainly young adults, very late onset cases are rare. Transient, small, salmon–pink, not itchy rashes, usually concurrent with fever, can drive diagnosis, along with major and minor criteria of Yamaguchi. Often patients have serositic involvement with pleuritis or pericarditis, with tamponade needing drainage. Such forms respond well only to steroid treatment. However, cases of fibrinous pericarditis as marked as the one described have not been described; the so important fibrinous component would made an eventual pericardiocentesis difficult. Although infrequent, it is a differential diagnosis that the cardiologist must consider in cases of refractory pericarditis and pericardial effusion.

Asetil Salisilik Asit Solüsyonlarında Ön Çimlendirmenin Havuç Tohumlarının Tuz Stresi Altında Çimlenme ve Çıkışı Üzerine Etkileri

Bu araştırmada asetil salisik asit (ASA) solüsyonun farklı dozlarında ön çimlendirmenin “Nantes” havuç çeşidi (Daucus corata L.) tohumlarının tuz stresi altında çimlenme ve çıkış performansları üzerine etkileri laboratuar koşullarında araştırılmıştır. Tohumlar, ASA solüsyonları içerisinde 24 saat süreyle iklim dolabında ön çimlendirme işlemine tabi tutulmuştur. Bu işlemden sonra ön çimlendirme ve kontrol grubu olarak iki gruba ayrılmıştır. Her iki grup 0, 50, 100 ve 150 mM NaCl stresine maruz bırakılarak, ASA uygulamasının tuzluk sterine tepkileri incelenmiştir. Araştırma sonucunda yüksek tuz konsantrasyonunun (150 mM NaCl) havuç tohumlarının çimlenmesini azalttığı, yüksek dozdaki ASA ön uygulamalarının tohumların çimlenme ve çıkış parametrelerini etkilediği belirlenmiştir. Sonuçlara göre ön uygulamalar arasında doz x tuz interaksiyonunda 150 mg/L ASA uygulmasında 0 ve 50 mM NaCl interaksiyonunda %93 ile en yüksek çimlenme oranı belirlenmiştir. ASA uygulamalarının, düşük ve yüksek tuzluluğa sahip yetiştirme ortamlarında tohumların çimlenme oranında artış sağladığı ve başarılı bir şekilde kullanılabileceği ön görülmüştür.

Low-Dose Aspirin for Venous Thromboembolism Prophylaxis is Associated With Lower Rates of Periprosthetic Joint Infection After Total Joint Arthroplasty

BackgroundAspirin as a venous thromboembolism (VTE) prophylactic agent has been shown to have antistaphylococcal and antibiofilm roles. Optimal acetylsalicylic acid (ASA) dosage would facilitate antimicrobial effects while avoiding over-aggressive inhibition of platelet antimicrobial function. Our purpose was to determine the periprosthetic joint infection (PJI) rate after total joint arthroplasty in patients receiving low-dose ASA (81 mg twice a day), in comparison to high-dose ASA (325 mg twice a day). MethodsWe conducted a retrospective cohort study between 2008 and 2020. Eligible patients were older than 18 years, underwent primary total joint arthroplasty, both total knee arthroplasty and total hip arthroplasty, had a minimum 30-day follow-up, and received a full course ASA as VTE prophylaxis. Patients’ records were reviewed for PJI, according to Musculoskeletal Infection Society criteria. Patients were excluded if they underwent revision arthroplasty, had a history of coagulopathy, or had an ASA regimen that was not completed. In total 15,825 patients were identified, 8,761 patients received low-dose ASA and 7,064 received high-dose ASA. ResultsThe high-dose cohort had a higher PJI rate (0.35 versus 0.10%, P = .001). This relationship was maintained when comparing subgroups comprising total knee arthroplasty (0.32 versus 0.06%, P = .019) or total hip arthroplasty (0.38 versus 0.14%, P = .035) and accounting for potentially confounding demographic and surgical variables (odds ratio = 2.59, 95% CI = 1.15-6.40, P = .028). ConclusionComparing low-dose to high-dose ASA as a VTE prophylactic agent, low-dose ASA had a lower PJI rate. This may be attributable to a balance of anti-infective properties of ASA and antiplatelet effects.

Impact of Early Treatment With High-Dose Intravenous Immunoglobulin on Incidence of Kawasaki Disease Complications in Iranian Children.

Objective: Kawasaki disease (KD) occurs in five-year-old or younger children. This study aimed to evaluate the impact of high-dose intravenous immunoglobulin plus acetylsalicylic acid therapy on the prevention and treatment of coronary artery lesions and to evaluate the impact of high-dose acetylsalicylic acid (ASA) on the hearing of the patients. Materials and methods: In this retrospective cohort study, 31 patients with KD were followed from January 2012 to December 2015. The clinical, para-clinical, color Doppler echocardiogram and audiometry results were evaluated. Results: Overall, seven cases (22.6%) developed coronary artery aneurysm (CAA) in the acute phase of the disease, of whom only two still had CAA at the end of the treatment (6%). One of the five children with CAA recovery had a delay in the onset of treatment and one of two patients with persistent CAA at the end of treatment was admitted within the first 10 days. There was no evidence-based abnormal liver biochemical test. None of the patients developed sensorineural hearing loss (SNHL) on audiometry tests conducted before and after treatment. Conclusion: Recovery of coronary artery lesions was 71.43% after 28 days of the onset of treatment. The distribution of coronary artery aneurysm was not different in terms of the time of the treatment initiation (P-Value = 0.371). None of the children had a sensorineural hearing loss (SNHL) 48 hours and 4 weeks after treatment.

P079 Multi-systemic inflammatory syndrome in children: skin tropism

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a severe immune-mediated syndrome that occurs after COVID-19 infection. It mainly affects children and presents several clinical aspects. The cutaneous and mucous signs are very much part of the diagnostic criteria. The aimisto describe the clinical and evolutionary aspects of the muco-cutaneous signs during MIS-C Patients and methods It was a descriptive retrospective study conducted over a period of 9 months (March 1, 2020 - December 31, 2020) including children admitted to COVID isolation unit with suspicion of MIS-C syndrome. Results We included 17 patients. The average age was 7 years (1–11 years). The sex ratio was 2.2 (11 boys and 6 girls). There was o history of dermatological disease has been reported. Fever was present in all patients. Mucosal signs were present in 13 patients. Conjunctival hyperemia without purulent secretions was noted in 12 patients. Conjunctivitis was bilateral in 11 cases. A rash was found in 10 cases. It was macular (6 cases), maculopapular (2 cases) and vesicular cluster in one 1 case. It was itchy in 2 cases. It was located in the limbs (7 cases), thorax and/or abdomen (5 cases), pelvis (4 cases), palms and/or soles (3 cases) and the face in one case. Cheilitis was found in 6 cases and stomatitis or glossitis in 5 cases. oEdema of the extremities was present in three patients and oedema of the face was noted in one patient. All children received intravenous immunoglobulin therapy combined with high-dose corticosteroids and acetylsalicylic acid at anti-aggregating doses. The course was marked by the disappearance of the muco-cutaneous signs without recurrence in all cases. Conclusion Mucocutaneous involvement is a characteristic manifestation of multisystem inflammatory syndrome. It is one of the various diagnostic criteria for this syndrome.

The Impact of Moderate-Dose Acetylsalicylic Acid in the Reduction of Inflammatory Cytokine and Prevention of Complication in Acute Phase of Kawasaki Disease: The Benefit of Moderate-Dose Acetylsalicylic Acid.

Background: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA. We aimed to evaluate the impact of different doses of ASA on inflammation control while minimizing adverse effects in the acute phase treatment of KD. Methods: The enrolled 323 patients with KD were divided into three groups according to ASA dose: moderate-dose (30–50 mg/kg/day), high-dose (80–100 mg/kg/day), and non-ASA. Results: High-dose ASA group showed a significantly shorter duration of fever from the start of treatment to remission than other groups. Baseline level and delta score of interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, and transforming growth factor β were not statistically different among the groups. The number of patients who received additional treatments in the non-ASA group was more than other groups. Coronary artery dilatation was not significantly different among the groups. One patient with high-dose ASA was diagnosed with Reye syndrome. Conclusion: Different doses of ASA did not show any differences in changes of inflammatory bio-makers and cytokines. However, high-dose ASA showed occurrence of Reye syndrome, and non-ASA showed intravenous immunoglobulin refractoriness. We suggest that moderate-dose ASA may be beneficial for the treatment of patients in the acute phase of KD.

Synergistic platelet inhibition between Omega-3 and acetylsalicylic acid dose titration; an observational study

BackgroundOmega-3 and acetylsalicylic acid (ASA) are two widely used “over-the-counter” drugs. Previous research has shown multiple electrode aggregometry (MEA) can detect ASA and varying Omega-3 platelet inhibiting effects. Synergistic platelet inhibiting effects of ASA and Omega-3 have been found using other methods than MEA. The aim of this study was to investigate the antiplatelet effects of Omega-3, and ASA synergism with MEA.MethodsTen healthy male volunteers ingested Omega-3 (1260 mg/day) for 5 days. MEA was used to analyse platelet function before and after Omega-3 intake. Aggregation was initiated using three different agonists and measured as area under the curve (AUC): adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and arachidonic acid (ASPI). Two concentrations of ASA were dose titrated ex vivo to 2 out of 3 ASPI test cells in order to measure synergism between Omega-3 and ASA.ResultsFollowing 5 days Omega-3 intake, ADP, TRAP and ASPI AUC did not change significantly. In vitro ASA before Omega-3 intake, reduced ASPI AUC < 30 U, indicating a strong platelet inhibiting effect. Below this AUC level, the 5 days Omega-3 intake increased ASPI-AUC with the ex vivo added low dose ASA (P = 0.02) and high dose ASA (P = 0.04).ConclusionsNo synergism between ASA and Omega-3 was found using the MEA ASPI test. The surprising increase in ASPI-AUC following Omega-3 intake and ex vivo ASA suggest that there are methodological issuses with the MEA ASPI test.Trial registrationTrial registration ISRCTN78027929. Registered 19 May 2015.

A Case Report of Exacerbation of Leg Ulcers Associated with Acute High-dose Acetylsalicylic Acid in a Patient with Klinefelter Syndrome

Klinefelter syndrome (KS) is the most frequent type of congenital sex-chromosomal disorder caused by at least one extra X chromosome and commonly treated with lifetime testosterone therapy. Ulcerative lesions on lower extremities may occur as a complication of KS. The pathogenesis of ulcers in KS patients has not been clarified on a molecular level. Here we present a case of leg ulcers exacerbation associated with the administration of a high dose of acetylsalicylic acid in a 63-year-old KS patient with karyotype 47,XXY undergoing testosterone replacement therapy for the last 20 years. The appearance of the ulcer on the patient's leg occurred during one week of high oral acetylsalicylic acid intake (1.2 g daily). The patient was advised to return to his standard daily dose of 0.1 g of acetylsalicylic acid and significant improvement of his leg ulcer was observed after two weeks. We hypothesize that testosterone-mediated nitric oxide balance in KS patient is perturbed under the condition of acute high-dose acetylsalicylic acid administration. We propose that small standard doses of approximately 0.1 g/day of acetylsalicylic acid have no apparent effect on nitric oxide status, whereas higher doses may cause dysregulation of nitric oxide production and/or utilization, creating conditions which may cause the appearance of leg ulcers in the KS patients.

Role of aspirin-triggered lipoxin A4, aspirin, and salicylic acid in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia.

Oxidative stress and inflammation are key events leading to pre-eclampsia, involved in several maternal deaths. Low doses of acetylsalicylic acid (ASA) are used in the prevention and treatment of pre-eclampsia. The synthesis of aspirin-triggered lipoxin (ATL) by cyclooxygenase-2 acetylation is an alternative mechanism of ASA, which could explain the effectiveness of ASA treatments. The aim of this study was to evaluate the role of ASA, salicylates, and ATL in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia. Plasma from 14 women with pre-eclampsia and 17 normotensive pregnant women was probed for inducing oxidative and inflammatory responses on endothelial cells and U937 promonocytes. The role of ATL, ASA, and salicylic acid (SA) on these events was evaluated. Plasma from women with pre-eclampsia induced TBARS and nitrotyrosine production on endothelial and U937 cells. Pre-treatment with both ATL and ASA decreased the TBARS production, while ATL decreased the nitrotyrosine. Pre-eclamptic plasma augmented the translocation of NF-kB on U937 cells, which decreased by a high dose of ASA and SA. Finally, the pre-eclamptic plasma increased the adhesion of leukocytes-PMN and monocytes-to endothelium, and we were able to determine a state of resolution of inflammation, since ATL decreased the PMN adhesion, and conversely, it increased the monocytes adhesion to endothelium. Together, these results suggest that ATL could explain the beneficial actions of ASA and support further research on mechanisms, real efficacy, and rational use of ASA in pre-eclampsia.

EFFECT OF PECTIN/MONTMORILLONITE INTESTINAL ADSORBENTS ON BLOOD BIOCHEMICAL PARAMETERS DURING CHRONIC TREATMENT WITH ACETYLSALICYLIC ACID

Chronic treatment with non-steroidal anti-inflammatory drugs such as acetylsalicylic acid may cause a number of adverse effects and chronic conditions. Intestinal adsorbents based on natural materials are used to prevent or treat various intoxications. In this study, it was described detoxification and protective effect of composite pectin/montmorillonite intestinal adsorbents in rats receiving high doses of acetylsalicylic acid. 60 Wistar rats received 100 mg/kg of acetylsalicylic acid without or together with composite intestinal adsorbents based on montmorillonite and 5%, 10%, and 20% pectin. After 16 days of the experiment, blood samples were collected to measure blood biochemistry profiles, including levels of total protein, albumin, glucose, cholesterol and liver enzymes. It was observed significant changes in blood biochemistry profile as well as in liver enzyme levels in rats receiving acetylsalicylic acid for 16 days. Concomitant administration of acetylsalicylic acid and composite intestinal adsorbents based on montmorillonite and 5%, 10%, and 20% pectin provided a protective effect as judged by recovery of blood biochemistry and liver enzyme profiles to control levels. The composite adsorbent with 20% pectin had maximum effect. Therefore, pectin/montmorillonite intestinal adsorbents can be used to decrease gastrointestinal irritation and adverse effects of drugs, such as acetylsalicylic acid.

High acetylsalicylic acid dosing in infants after modified Blalock-Taussig shunt.

Shunt-related adverse events are frequent in infants after modified Blalock-Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock-Taussig. In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock-Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose. There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2-23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3-71), p&lt;0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7-10), p=0.16] was not associated with decrease in these events. High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock-Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock-Taussig.

Pharmacology of non-opioid analgesics

Due to high prescription rates as well as the frequent use as over the counter drugs, it is of interest to consider non-opioid analgesics when evaluating the quality and appropriateness of agiven overall medication. This article sums up the basic pharmacology and main adverse effects of these analgesics. Non-opioids can be further classified according to their additional mechanisms of action besides analgesia. High-dose acetylsalicylic acid, traditional nonsteroidal anti-inflammatory drugs, and coxibs exhibit antipyretic and anti-inflammatory properties. Acetaminophen and metamizole (dipyrone) are analgesics and antipyretic agents, while metamizole exhibits also spasmolytic effects. Capsaicin and intrathecal ziconotide are pure analgesics.

Antiplatelet therapy and the risk of ischemic and hemorrhagic complications associated with Pipeline embolization of cerebral aneurysms: a systematic review and pooled analysis

BackgroundPipeline embolization devices (PEDs) are increasingly used in the treatment of cerebral aneurysms. Yet, major ischemic or hemorrhagic complications after PED treatment associated with antiplatelet regimens are not well-established.ObjectiveTo investigate...

Aspirin Dose in Kawasaki Disease: The Ongoing Battle.

Kawasaki disease (KD) is an acute childhood vasculitis that may result in coronary aneurysms. Treatment of KD with a single infusion of 2 gm/kg intravenous immunoglobulin (IVIG) is well established, but acetylsalicylic acid (ASA) dose remains controversial. Our primary objective was to determine the difference in the incidence of IVIG resistance between 2 ASA doses. Our secondary objective was to compare the duration of hospital stay and the incidence of coronary artery aneurysm. We reviewed charts of patients with KD from 2 Canadian centers to assess the impact of ASA dose on IVIG resistance (operationally defined as administration of a second dose of IVIG). Both centers used standard IVIG dosing, but center 1 used low-dose ASA from diagnosis (3-5 mg/kg/day) while center 2 used initial high-dose ASA (80-100 mg/kg/day). There were no significant differences in baseline characteristics between the 2 centers. Retreatment with a second dose of IVIG was required in 28 of 122 patients (23%) treated with low-dose ASA, and in 11 of 127 patients (8.7%) treated with high-dose ASA in center 1 and center 2, respectively (P = 0.003). After adjusting for confounders, low-dose ASA was associated with higher odds of IVIG resistance (OR 3.2 [95% confidence interval 1.1, 9.1]). The mean duration of hospital stay was 4.1 and 4.7 days, respectively (P = 0.37). Coronary artery aneurysms were seen in 2 of 117 and 6 of 125 patients from centers 1 and 2, respectively (P = 0.28). Low-dose ASA was associated with 3-times higher odds of IVIG retreatment compared to high-dose ASA, with no significant difference in duration of hospital stay or incidence of coronary artery aneurysms.

Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies.

Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies.

Effects of low and high doses of acetylsalicylic acid on penicillin-induced epileptiform activity.

The most common headache associated with epilepsy occurs after seizure activity and is called a postictal headache. Therefore, the objective of this study was to investigate the effects of low and high doses acetylsalicylic acid (aspirin) on a penicillin-induced experimental epilepsy model. Adult male Wistar rats (n = 28, weighing 220 ± 40 g) were used in the experiments. The rats were divided into four groups as Control, Penicillin, Aspirin 150 mg/kg, Aspirin 500 mg/kg. Seizure activity was triggered by an intracortical injection of penicillin G potassium (500 IU/2.5 μl) into the sensory motor cortex. An electrocorticogram was recorded by using conductive screw electrodes. Aspirin at the doses of 500 mg/kg and 150 mg/kg was given intraperitoneally (ip) 30 min after penicillin administration. Anticonvulsant activity appeared at the 30th and 40th min after an intracortically administered injection of penicillin in the groups given aspirin doses of 500 mg/kg (ip) and 150 mg/kg (ip) respectively. The amplitude of epileptiform activity at both doses of aspirin decreased but the difference was not statistically significant. The results of the present study suggest that low and high doses of aspirin may decrease epileptiform activity in penicillin-induced epilepsy. Aspirin might be suggested for headache associated with epilepsy.

CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease.

Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD. We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression. The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types. This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.

Revisiting the role of steroids and aspirin in the management of acute Kawasaki disease.

Kawasaki disease is an acute multisystem childhood vasculitis with a predilection for the coronary arteries. The role of corticosteroids and acetyl salicylic acid (ASA) in the treatment of acute Kawasaki disease are matters of ongoing debate and changing attitudes from one extreme to the other. Recent work has provided new evidence to guide our thinking about these two therapeutic agents, which will be the focus of this review. Corticosteroids are effective and well tolerated in Kawasaki disease, both as initial adjunctive treatment in those at high-risk for poor outcome, and as rescue therapy after failed intravenous immunoglobulin (IVIG).Higher doses of ASA (> 30 mg/kg/day) in the acute phase of Kawasaki disease, have no clear benefit over antiplatelet doses in improving coronary outcome. Corticosteroids should be used in patients at high-risk for poor coronary outcome, and in patients who fail IVIG. The absence of widely applicable and validated risk-scoring systems in Kawasaki disease outside of Japan remains a limiting factor to identify high-risk children. Current evidence does not demonstrate any advantage of high-dose over low-dose ASA in the acute phase of Kawasaki disease, in preventing coronary artery aneurysms.

Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice

Background: The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied.Objectives and methods: To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case–control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0.Results: Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32–5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms.Conclusions: The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.