Calcium carbonate supplementation for the prevention of preeclampsia in high-risk pregnant women: a randomized clinical trial protocol.

BACKGROUND: Preeclampsia (PE) is a significant cause of maternal mortality worldwide, affecting 2% to 8% of pregnancies. The World Health Organization recommends the use of low-dose acetylsalicylic acid (100 mg of aspirin) and 1.5 to 2 g of calcium carbonate during pregnancy to prevent PE. However, robust evidence supporting the efficacy of calcium supplementation is still needed. This study aims to assess the efficacy of calcium carbonate in preventing preeclampsia in high-risk pregnant women. METHODS: A triple-blind, randomized clinical trial will be conducted at an outpatient clinic in Brazil between May 2024 and March 2026. Pregnant women at high risk of developing preeclampsia and with low dietary calcium intake will be randomly assigned to one of three groups: one group will receive calcium carbonate capsules (commercially available in Brazil) along with 100 mg of aspirin; the second group will receive calcium carbonate derived from Crassostrea sp. along with 100 mg of aspirin; and the control group will receive a placebo alongside 100 mg of aspirin. The primary outcome is the diagnosis of preeclampsia during pregnancy, while secondary outcomes evaluate maternal and fetal health indicators. DISCUSSION: This trial seeks to generate evidence on the efficacy of calcium carbonate in preeclampsia prevention, with a focus on comparing industrial calcium carbonate with calcium carbonate sourced from Crassostrea sp., a more sustainable alternative. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of the Federal University of Sergipe and registered in the Brazilian Registry of Clinical Trials (ReBEC), under the ID RBR-7hqhj3y. Registered on November 16, 2023.

Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process.

BACKGROUND: Severe malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65). METHODS: C57BL/6 mice were randomly divided into control (C) and PbNK65 infected groups and were inoculated with uninfected or 104 infected erythrocytes, respectively. Then, the animals were treated with DHA (3 mg/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7 days and with ASA (100 mg/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses. RESULTS: PbNK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (ΔP1, L) and viscoelastic (ΔP2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA + ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in ΔP1, L and ΔP2, L compared to Pb + DMSO. Also, combined treatment with DHA + ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi. CONCLUSIONS: Therapy with ASA maintained lung morpho-functional impairment triggered by PbNK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases.

Aspirin use in patients with elevated lipoprotein(a): Impact on cardiovascular events and bleeding.

The role of aspirin in cardiovascular primary prevention remains controversial. There are physiological reasons to explore its potential benefits in patients with high levels of lipoprotein(a) [Lp(a)], mainly due to its antifibrinolytic properties and interactions with platelets. The primary objective of this systematic review was to evaluate the cardiovascular benefits and bleeding risks associated with aspirin use in patients who have elevated Lp(a) levels but no history of cardiovascular disease. This systematic review was conducted following PRISMA guidelines. We performed a literature search to identify studies assessing the cardiovascular benefits and bleeding risks of aspirin use in patients with elevated Lp(a) levels (or a related genetic variant) who have no history of cardiovascular disease. Five studies (49,871 individuals) were considered for this systematic review. Three studies assessed the impact of aspirin use in relation to genetic variants associated with elevated Lp(a) levels (SNP rs379822), while the remaining two studies directly measured plasma levels of Lp(a). The endpoints evaluated varied among the studies. Overall, the findings consistently show that carriers of the apolipoprotein(a) variant or patients with Lp(a) levels > 50 mg/dL experience a reduction in cardiovascular risk with aspirin use. No significant bleeding issues were observed, although such events were reported in only two studies. This systematic review suggests that aspirin use in patients with elevated Lp(a) levels and no prior cardiovascular history may reduce cardiovascular risk. The available data on bleeding risk is insufficient.

A Survey of Availability and Affordability of Polypills for Cardiovascular Disease in Selected Countries.

Background: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally. Methods: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply. Results: Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country. Conclusion: Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Direct oral anticoagulants in embolic stroke of undetermined source: an updated meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin).

Patients with diabetes face a 2-4-fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single-center, open-label, sequence randomized, 2 × 2 crossover, single-dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed-dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono-drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24-hour period following administration and were analyzed for metformin and salicylic acid using high-performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0 -t), and (area under the plasma drug concentration-time cruve from 0 up to infinity (AUC0 ∞) data were within the range of 80%-125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono-drugs. There were no adverse events or adverse reactions reported throughout the study.

Metabolic syndrome induces benefits in mice experiencing severe sepsis, comparable to the effects of low-dose aspirin pretreatment in septic mice lacking metabolic syndrome.

BACKGROUND: Sepsis is a complex condition characterized by systemic host inflammation caused by an infection. Experimental and observational studies indicate that obesity, one of the components of metabolic syndrome (MetS), or aspirin (ASA) treatment could be associated with sepsis survival. However, the effects of ASA on septic mice with MetS-induced conditions have not been explored. METHODS: Swiss mice were administered monosodium glutamate (MSG) (4 mg/kg) during their first 5 days of life for MetS induction, while the control mice received an equimolar saline solution. MetS was validated in male mice on their 60th day of life. ASA treatment was administered for 15 days prior to sepsis (40 mg/kg). On the 75th day, sepsis was induced in MetS and control mice through cecal ligation and puncture (CLP). The effects of ASA on septic mice with MSG-induced MetS were assessed by determining survival rates, quantification of nitric oxide (NO), and cytokine levels in the plasma, while correlating these data with hematological, blood glucose and cardiovascular parameters. RESULTS: MetS was validated by Lee-Index (3 body weight/naso-anal length×1000), hypertension, and hyperglycemia in animals receiving MSG as neonates. In control animals, severe sepsis promoted hypoglycemia, which was associated with mortality, as well as increased plasma NO levels, hypotension, hematological alterations, and elevation of proinflammatory cytokines. In contrast, MetS and pre-treatment with ASA were able to prevent sepsis-related alterations. CONCLUSIONS: MetS and ASA pre-treatment provided protection against severe sepsis. However, ASA was ineffective in mice with MetS undergoing severe sepsis.

Safety of metamizole (dipyrone) for the treatment of mild to moderate pain-an overview of systematic reviews.

Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.

Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative. AIMS: We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms. RESULTS: A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality. CONCLUSIONS: DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA.

Current obstetric outcomes in Jamaican women with sickle hemoglobinopathy - a balance of risks for aspirin?

OBJECTIVES: Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes. METHODS: A retrospective comparative analysis of HbSS, HbSC and HbSßThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted. RESULTS: Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSßThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5-32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4-16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1-8.9; p=0.037) and preterm birth (OR=2.6, 1.2-5.8; p=0.018) compared to HbSC and HbSßThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04-0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03-0.9, p=0.03)). CONCLUSIONS: HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes.

Effects of major analgesics on male fertility: A systematic literature review.

OBJECTIVE: To verify, based on a systematic literature review, the effects of the main analgesics on male fertility. DATA SOURCES: The studies were analyzed from the PubMed, SciELO and LILACS databases. STUDY SELECTION: The articles selected for the present review included: cohort studies; cross-sectional studies, clinical trials; complete studies; studies with animal models that addressed the proposed theme and that were published within the stipulated period from March 1, 2013, to March 31, 2023, in English, Portuguese and Spanish. These would later have to go through inclusion stages such as framing the type of study and exclusion criteria. DATA COLLECTION: Author's name, year of publication, study population, number of patients, analgesic, administration time, dose, and effect. CONCLUSIONS: There are in vitro and in vivo studies that link paracetamol and ibuprofen to endocrine and seminal changes that are harmful to male fertility. However, more clinical research is needed to determine the doses and timing of administration that affect fertility. The effects of aspirin on male fertility are still unclear due to the lack of studies and consistent methodologies. There is not enough research on dipyrone and its relationship with male fertility, requiring more studies in this area.

Uso de aspirina en prevención primaria cardiovascular: es tiempo de cambiar el paradigma / Aspirin use for primary cardiovascular prevention: time for a paradigm shift

La Aspirina es una droga ampliamente utilizada con un protagonismo indiscutido en el escenario de la prevención secundaria. Sin embargo, el rol de este medicamento en prevención primaria es aún motivo de discusión. Los primeros ensayos que evaluaron la Aspirina en prevención primaria sugerían reducciones en el infarto agudo al miocardio y el accidente cerebrovascular -aunque no en la mortalidad- con un riesgo no despreciable de hemorragia mayor. Esto llevó a diversas sociedades científicas a recomendar su prescripción sólo en aquellos individuos con alto riesgo de eventos cardiovasculares. Desde el año 2018 en adelante, surgen diversos ensayos aleatorizados que han cuestionado estas indicaciones, mostrando beneficios clínicos muy discretos o ausentes. El objetivo de esta revisión es realizar un análisis histórico de la evidencia sobre el rol de la Aspirina en prevención primaria y resumir las recomendaciones actuales en este escenario.

Aspirin is widely used with a clear role in secondary prevention of cardiovascular diseases. However, its benefit in primary prevention is still a matter of discussion. The first trials evaluating Aspirin for primary prevention suggested reductions in acute myocardial infarction and stroke (although not in mortality) but with a non-negligible risk of major bleeding. This led to aspirin being recommended by various scientific societies, albeit limited to individuals at high risk of cardiovascular events. Since 2018 various randomized trials in primary prevention showed minimal or no beneficial effects of aspirin thus questioning its indication for this purpose. The aim of this review is to make an historical analysis of the evidence for the role of Aspirin in primary prevention and suggest modified recommendations for these subjects.

Evaluation of the Effect of Low-dose Aspirin on the Prevention of Preterm Delivery in Women with a History of Spontaneous Preterm Delivery / Avaliação do efeito da aspirina em baixa dose na prevenção do parto prematuro em mulheres com história de parto prematuro espontâneo

Abstract Objective Currently, uteroplacental vascular disorders are considered one of the main mechanisms of spontaneous preterm delivery (PTD). Low-dose aspirin is used to prevent pre-eclampsia, which has a similar mechanism; hence, the present study aimed to investigate the effect of low-dose aspirin on the prevention of PTD in women with a history of spontaneous PTD. Methods The present pilot randomized clinical trial was conducted on 54 pregnant women in the aspirin group (taking 80 mg daily until the 36th week and classic treatment) and 53 patients in the control group (only receiving classic treatment). Results Forty-three patients (40%) presented before 37 weeks due to symptoms of PTL. Preterm delivery (< 37 weeks) occurred in 28 patients (26%), and there was no significant difference between the aspirin and control groups (10 patients [19%] and 18 patients [34%], respectively; p = 0.069). The time of preterm delivery was early (< 34 weeks) in 6 patients (21%), and its cause was spontaneous labor in 23 patients (82%) which was not significantly different between the two groups (p > 0.05). Out of 40 patients with spontaneous labor, 25 patients (63%) had a PTD, which was significantly lower in the aspirin group than in the control group (9 patients [45%] versus 16 patients [80%], respectively; p = 0.022). Conclusion The findings of the present study demonstrated that despite the reduction in the incidence of PTD using low-dose aspirin, the reduction rate was not statistically significant. On the other hand, in patients with spontaneous labor prone to PTD, aspirin was effective in reducing the incidence of PTD.

Resumo Objetivo Atualmente, os distúrbios vasculares uteroplacentários são considerados um dos principais mecanismos de parto prematuro espontâneo (PTD). A aspirina em baixa dose é usada para prevenir a pré-eclâmpsia, que tem um mecanismo semelhante; portanto, o presente estudo teve como objetivo investigar o efeito da aspirina em baixa dosagem na prevenção de PTD em mulheres com história de PTD espontâneo. Métodos O presente ensaio clínico piloto randomizado foi realizado em 54 gestantes do grupo aspirina (tomando 80 mg diários até a 36ª semana e tratamento clássico) e 53 pacientes do grupo controle (somente tratamento clássico). Resultados Quarenta e três pacientes (40%) apresentaram-se antes de 37 semanas devido a sintomas de PTL. O parto prematuro (< 37 semanas) ocorreu em 28 pacientes (26%) e não houve diferença significativa entre os grupos aspirina e controle (10 pacientes [19%] e 18 pacientes [34%], respectivamente; p = 0,069). O tempo de parto prematuro foi precoce (< 34 semanas) em 6 pacientes (21%) e sua causa foi trabalho de parto espontâneo em 23 pacientes (82%) que não foi significativamente diferente entre os dois grupos (p > 0,05). Das 40 pacientes com trabalho de parto espontâneo, 25 pacientes (63%) tiveram PTD, que foi significativamente menor no grupo aspirina do que no grupo controle (9 pacientes [45%] versus 16 pacientes [80%], respectivamente; p = 0,022). Conclusão Os achados do presente estudo demonstraram que, apesar da redução na incidência de DPT com o uso de aspirina em baixa dosagem, a taxa de redução não foi estatisticamente significativa. Por outro lado, em pacientes com trabalho de parto espontâneo propensas a PTD, a aspirina foi eficaz na redução da incidência de PTD.

VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study.

BACKGROUND AND AIMS: Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR - rs61722009) of the endothelial nitric oxide synthase (eNOS) on the drug response, we assessed the influence of this polymorphism for the risk of upper gastrointestinal bleeding (UGIB). METHODS: A case-control study, including 200 cases and 706 controls, was conducted in a Brazilian hospital complex. Cases were participants with UGIB diagnosis. Controls were participants admitted to surgical procedures not related to gastrointestinal problems. The 4b/4a VNTR was determined through polymerase chain reaction followed by fragment analysis. Conditional logistic regression models were designed. The additive interaction between the presence of the 4b/4a VNTR variant and the use of low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) was calculated by fitting the Cox regression model through the parameters of Synergism index (S) and Relative Excess Risk Due To Interaction (RERI). RESULTS: The presence of the 4b/4a VNTR variant did not increase the risk of UGIB: carriers of the 4a/4a genotype (OR=0.37, 95%CI: 0.09-1.45) and of the variant allele "4a" (OR=0.91, 95%CI: 0.55-1.51). The risk of UGIB in LDA users carriers of the wild genotype (OR=4.96, 95%CI: 2.04- 2.06) and the variant allele "4a" (OR=3.49, 95%CI: 1.18-10.38) is similar, as well as for NSAID users carriers of the wild genotype (OR=5.73, 95%CI: 2.61-12.60) and variant allele "4a" (OR=5.51, 95%CI: 1.42-15.82). No additive interaction was identified between the presence of the genetic variant and the use of LDA [RERI: -1.44 (95%CI: -6.02-3.14; S: 0.63 (95%CI: -1.97-1.15)] and NSAIDs [RERI: -0.13 (95%CI: -6.79-6.53; S: 0.97 (95%CI: -0.23-4.19)] on the UGIB risk. CONCLUSION: Our data suggests that there is no increase in the magnitude of UGIB risk in LDA and NSAIDs users' carrying the variant allele "4a".

Effects of different acetylsalicylic acid doses on body organs, histopathology, and serum biochemical parameters in broiler birds / Efeito de diferentes doses de ácido acetil salicílico nos orgãos corpóreos, histopalogia e parâmetros bioquímicos sorológicos em frangos de corte

The poultry industry suffers from various diseases or stresses. In poultry, apart from being antipyretic, acetylsalicylic acid (ASA) is widely used to cope with different issues including heat stress, and respiratory and digestive orders. This study evaluated the beneficial and toxic effects of ASA at different dose levels in broiler birds. To evaluate these toxic and beneficial effects it is necessary to examine the physical and serum biochemical parameters as well as the histopathological changes with tissue sections taken from broiler birds under experimental trial. This study was conducted on 60 one-day-old broiler chicks purchased from a local market in Faisalabad. Chicks were reared for the first 14 days under similar conditions. On the 15th day, birds were randomly divided into 4 groups (1-4) with 15 birds in each group. Group 4 was kept as control, while groups 1, 2, and 3 were treated with ASA at the dose of 300, 600, and 1200 mg/L of drinking water for 21 days. There were 3 samplings performed at 21, 28, and 35 days post-treatment. The live body weight and carcass weight were noted on each sampling. All the visceral organs were recorded for gross pathological changes. The serum samples were collected for biochemical evaluation. Histopathology of all the visceral organs was performed to observe the microscopic changes. A significant (P<0.05) increase in live body weight at a 300mg/L dose was noted after the first 2 samplings. A significant (P<0.05) increase in the relative organ weight was recorded at 1200 mg/L. The groups treated with ASA 600 and 1200 mg/L showed increased (P<0.05) AST, ALT, and creatinine levels from that of the control group. The group treated with 1200 mg/L of ASA showed increased (P<0.05) urea, serum total protein, and albumin level in all the samplings. Histopathological changes revealed swollen hepatocytes, increased sinusoidal spaces in the liver, congestion and abnormal glomerular spaces in the kidney, congestion and alveolar disruption in the lungs, and generation of villi and cellular degeneration in the intestine in a high-dose group. The study concluded that ASA at a low dose can be used for a long time in broilers and has a growth promontory role, while high-level doses cause hepatorenal toxicity.(AU)

A indústria avícola é afetada por diversas doenças ou estresses. Particularmente devido às aves serem antipiréticas. O ácido acetil salicílico (AAS) é largamente utilizado com diferentes objetivos que incluem o controle do estresse calórico, bem como a atividade respiratória e digestiva. O propósito deste estudo foi a avaliação dos efeitos benéficos e tóxicos do emprego de diferentes dosagens do AAS em frangos de corte. As variáveis analisadas foram: exame físico, parâmetros bioquímicos, bem como as alterações histopatológica em seções de tecidos colhidas das aves em um ensaio experimental. O estudo foi conduzido em 60 frangos de corte com um dia de idade adquiridos em um mercado local de Faisalabad que foram recriados nos primeiros 14 dias em idênticas condições. Então no 15º dia as aves foram distribuídas randomicamente em quatro grupos identificados pelos números 1 a 4, com 15 aves em cada grupo. O grupo 4 foi mantido como grupo controle e os grupos 1, 2 e 3 foram tratados com AAS, respectivamente, nas doses de 300, 600 e 1200 mg/L de água de bebida, durante 21 dias. Foram realizadas três amostragens nos dias 21, 28 e 35 pós-tratamento. O peso vivo corpóreo e da carcaça foi registrado em cada amostragem. Em todos os órgãos viscerais foi analisada a presença de alterações patológicas. As amostras de soro sanguíneo foram colhidas para a avaliação bioquímica. O exame histopatológico de todos os órgãos viscerais foi realizado para a observação de alterações microscópicas. A partir da segunda amostragem foi observado um aumento significante (p<0,05) no peso corpóreo na dosagem de 300mg/L. Um significante aumento no peso relativo dos órgãos foi registrado na dosagem de 1200 mg/L. Os grupos tratados com dosagens de 600 e 1200 mg/L de AAS, apresentaram aumento significante dos níveis de AST, ALT e de creatinina quando comparados ao grupo controle. O grupo tratado com 1200 mg/L de AAS apresentou um aumento significante (P,0,05) de uréia, proteína sérica total e de albumina em todas as amostragens. No grupo de alta dosagem foram observados alterações histopatológicas constituídas por aumento dos hepatócitos, aumento dos espaços sinusoidais no fígado, congestão e anormalidades nos espaços glomerulares nos rins, congestão e ruptura alveolar nos pulmões, degeneração das vilosidades e celular nos intestinos A conclusão obtida foi que em frangos de corte uma baixa dosagem do AAS pode ser utilizada por um período de longa duração, apresentando um efeito promotor do crescimento, contudo as doses elevadas determinam toxicidade hepática e renal.(AU)

Síndrome inflamatorio multisistémico post COVID-19 con afectación miocárdica: reporte de caso / Clinical case: post-COVID multisystem inflammatory syndrome with myocardial involvement / Síndrome inflamatória multissistêmica pós-COVID com acometimento do miocárdio (SIMC): relato de caso

En abril de 2020, durante el pico de la pandemia COVID-19 producida por el coronavirus emergente SARS-CoV-2, en el Reino Unido se comunicaron casos de shock hiperinflamatorio de características similares a la enfermedad de Kawasaki y el síndrome de shock tóxico en un grupo de ocho niños. El Royal College of Pediatrics and Child Health lo denominó síndrome inflamatorio multisistémico pediátrico temporalmente asociado con COVID-19 (SIM-C). Actualmente, el SIM-C es una enfermedad infrecuente, solapada con otras entidades, que requiere una alta sospecha clínica para identificarlo oportunamente. El síndrome inflamatorio multisistémico temporal asociado con SARS-CoV-2 pediátrico (PIMST) es una nueva entidad clínica con un amplio espectro de presentación postexposición al virus, inmunomediado con hiperinflamación y activación de una tormenta de citoquinas. Ocurre típicamente entre la segunda y cuarta semana de evolución. Se describen marcadores de inflamación característicamente elevados, como son la ferritina, proteína C reactiva (PCR), velocidad de eritrosedimentación (VES), lactato deshidrogenasa y dímero-D, asociados a neutropenia, linfopenia y anemia. La Organización Mundial de la Salud (OMS) define: caso a menores de 19 años con fiebre ≥3 días, marcadores inflamatorios elevados, evidencia de infección por SARS-CoV-2 y ninguna otra etiología microbiana; con afectación de al menos dos sistemas: dermatológico (rash, conjuntivitis no exudativa, inflamación mucocutánea), hemodinámico (hipotensión, shock), cardíaco (disfunción de miocardio, pericardio, valvular o coronario), hematológico (coagulopatía), digestivo (vómitos, diarrea, dolor abdominal). Considerando la gravedad de esta nueva entidad, es necesario el reconocimiento oportuno y referencia temprana para atención especiaizada y tratamiento oportuno.

Summary: In April 2020, during the peak of the COVID-19 pandemic caused by the emerging coronavirus SARS-CoV-2, 8 children reported cases of hyperinflammatory toxic shock with characteristics similar to Kawasaki disease and syndrome in the United Kingdom. The Royal College of Pediatrics and Child Health has called it pediatric Multisystem Inflammatory Syndrome (MIS) temporally associated with COVID-19. Currently, MIS-C is a rare disease, overlapping with other conditions, which requires a high clinical suspicion for its timely identification. Pediatric SARS-CoV-2-associated temporary multisystem inflammatory syndrome (TMIS-C) is a new clinical entity with a broad spectrum of presentation after exposure to the virus, immune-mediated with hyperinflammation and activation of a cytokine storm. It typically occurs between the 2nd to 4th week of evolution. Characteristically elevated markers of inflammation are described, such as ferritin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase and D-dimer, associated with neutropenia, lymphopenia and anemia. The World Health Organization (WHO) defines it as: a case under 19 years of age with fever ≥ 3 days, elevated inflammatory markers, evidence of SARS-CoV-2 infection and no other microbial etiology; with involvement of at least 2 systems: dermatological (rash, non-exudative conjunctivitis, mucocutaneous inflammation), hemodynamic (hypotension, shock), cardiac (myocardial, pericardial, valvular, or coronary dysfunction), hematologic (coagulopathy), digestive (vomiting, diarrhea, abdominal pain) Considering the seriousness of this new entity, timely recognition and early referral for specialized care and timely treatment are key.

No mês de abril de 2020, durante o pico da pandemia de COVID-19 causada pelo emergente coronavírus SARS-CoV-2, 8 casos de crianças com choque hiperinflamatório com características semelhantes à doença e síndrome de Kawasaki foram relatados no Reino Unido. O Royal College of Pediatrics and Child Health nomeou-o como síndrome inflamatória multissistêmica pediátrica (MIS) temporariamente associada ao COVID-19. Atualmente, o SIM-C é uma doença rara, sobrepondo-se a outras entidades, o que requer alta suspeição clínica para sua identificação oportuna. A síndrome inflamatória multissistêmica temporária associada ao SARS-CoV-2 pediátrico (SIMT) é uma nova entidade clínica com amplo espectro de apresentação após exposição ao vírus, imunomediada com hiperinflamação e ativação de uma tempestade de citocinas. Geralmente ocorre entre a 2ª a 4ª semana de evolução. São descritos marcadores de inflamação caracteristicamente elevados, como ferritina, proteína C reativa (PCR), velocidade de hemossedimentação (VHS), lactato desidrogenase e D-dímero, associados a neutropenia, linfopenia e anemia. A Organização Mundial da Saúde (OMS) a define como: caso de menor de 19 anos com febre ≥ 3 dias, marcadores inflamatórios elevados, evidência de infecção por SARS-CoV-2 e nenhuma outra etiologia microbiana; com envolvimento de pelo menos 2 sistemas: dermatológico (erupção cutânea, conjuntivite não exsudativa, inflamação mucocutânea), hemodinâmica (hipotensão, choque), cardíaca (disfunção miocárdica, pericárdica, valvar ou coronariana), hematológica (coagulopatia), digestiva (vômitos, diarreia, dor abdominal) Considerando a gravidade dessa nova entidade, é necessário o reconhecimento oportuno e encaminhamento precoce para atendimento especializado e tratamento oportuno.

Effect of diabetic kidney disease on therapeutic strategies for coronary artery disease: ten year follow-up.

BACKGROUND: The best treatment for coronary artery disease (CAD) in patients with type 2 diabetes (DM2) and chronic kidney disease is unknown. METHODS: This retrospective study included MASS registry patients with DM2 and multivessel CAD, stratified by kidney function. Primary endpoint was combined of mortality, myocardial infarction, or additional revascularization. RESULTS: Median follow-up was 9.5 years. Primary endpoint occurrences among strata 1 and 2 were 53.4% and 40.7%, respectively (P=.020). Mortality rates were 37.4% and 24.6% in strata 1 and 2, respectively (P<.001). We observed a lower rate of major adverse cardiovascular events (MACE) (P=.027 for stratum 1 and P<.001 for stratum 2) and additional revascularization (P=.001 for stratum 1 and P<.001 for stratum 2) for those in the surgical group. In a multivariate analysis, eGFR was an independent predictor of MACE (P=.034) and mortality (P=.020). CONCLUSIONS: Among subjects with DM2 and CAD the presence of lower eGFR rate was associated with higher rates of MACE and mortality, irrespective of treatment choice. CABG was associated with lower rates of MACE in both renal function strata. eGFR was an independent predictor of MACE and mortality in a 10-year follow-up.

Platelet Reactivity in Patients With Acute Coronary Syndromes Awaiting Surgical Revascularization.

BACKGROUND: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. OBJECTIVES: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. METHODS: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). RESULTS: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003). CONCLUSIONS: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267).

Risk of Early Bleeding with Dual Antiplatelet Therapy in Acute Stroke and Transient Ischemic Attack Regardless of NIHSS Admission.

BACKGROUND: Dual antiplatelet therapy (DAT) is a therapeutic option for patients with minor ischemic stroke (IS) or transient ischemic attack (TIA). No study has evaluated the incidence of early bleeding in patients with moderate to major ischemic stroke. The current study aimed to analyze both the frequency of early bleeding and hospital morbidity related to DAT for either acute IS or TIA regardless of admission National Institute of Health Stroke Scale (NIHSS) score. METHODS: This was a retrospective analysis based on data collected from a prospective data bank of a single center. We included patients who underwent DAT in the first 24 hours of symptom onset with a loading dose (aspirin 300 mg + clopidogrel 300 mg) on the first day, followed by a maintenance dose (aspirin 100 mg + clopidogrel 75 mg). We analyzed intracranial and/or extracranial hemorrhage that had occurred during the hospital admission, symptomatic bleeding, modified Rankin Scale (mRS) score at discharge, and death rates as outcomes. RESULTS: Of the 119 patients analyzed, 94 (79 %) had IS and 25 (21 %) had TIA. Hemorrhage occurred in 11 (9.2 %) and four (3.4 %) patients with TIA or NIHSS ≤ 3, respectively, although none were symptomatic. Patients with bleeding as a complication had higher admission NIHSS [4 (3-7) vs. 2 (1-4), p = 0.044] and had higher mRS at discharge (mRS 2 [1-5] vs. mRS 1 [0-2], p = 0.008). These findings did not indicate increased mortality, as one (9 %) patient died from bleeding and two (1.8 %) patients died without bleeding (p = 0.254). CONCLUSION: DAT seems to be a safe therapy in patients regardless of admission NIHSS if started within the first 24 h after symptom onset because only 1.6 % of patients had symptomatic bleeding.