BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

暂无摘要。

Preeclampsia is a syndrome that continues to be a major contributor to maternal and neonatal mortality, especially in low-income countries. Low-dose aspirin reduces the risk of preeclampsia, but the mechanism is still unknown. Risk factors to identify women at risk of preeclampsia are based on clinical characteristics. Women identified as high-risk would benefit from aspirin treatment initiated, preferably at the end of the first trimester. Current efforts have largely focused on developing screening algorithms that incorporate clinical risk factors, maternal biomarkers, and uterine artery Doppler evaluated in the first trimester. However, most studies on preeclampsia are conducted in high-income settings, raising uncertainties about whether the information gained can be totally applied in low-resource settings. In low- and middle-income countries, lack of adequate antenatal care and late commencement of antenatal care visits pose significant challenges for both screening for preeclampsia and initiating aspirin treatment. Furthermore, the preventive effect of first-trimester screening based on algorithms and subsequent aspirin treatment is primarily seen for preterm preeclampsia, and reviews indicate minimal or no impact on reducing the risk of term preeclampsia. The lack of evidence regarding the effectiveness of aspirin in preventing term preeclampsia is a crucial concern, as 75% of women will develop this subtype of the syndrome. Regarding adverse outcomes, low-dose aspirin has been linked to a possible higher risk of postpartum hemorrhage, a condition as deadly as preeclampsia in many low- and middle-income countries. The increased risk of postpartum hemorrhage among women in low-income settings should be taken into consideration when discussing which pregnant women would benefit from the use of aspirin and the ideal aspirin dosage for preventing preeclampsia. In addition, women\'s adherence to aspirin during pregnancy is crucial for determining its effectiveness and complications, an aspect often overlooked in trials. In this review, we analyze the knowledge gaps that must be addressed to safely increase low-dose aspirin use in low- and middle-income countries, and we propose directions for future research.

Our study aimed to investigate the clinical features of recurrent preeclampsia (rPE) and evaluate the preventive effect of low-dose aspirin (LDA) in rPE. We retrospectively analyzed the data of 109 patients who experienced preeclampsia in two consecutive pregnancies and delivered at Peking University First Hospital from January 2016 to December 2022. We analyzed the pregnancy outcomes of patients with rPE and assessed whether the use of LDA during pregnancy could improve these outcomes. Our results revealed that patients with rPE had a higher body mass index (BMI) and a higher incidence of diabetes during pregnancy compared to their first onset of preeclampsia (29.01 ± 4.70 kg/m2 vs. 27.13 ± 4.25 kg/m2, P < 0.05; 11.01% vs. 1.83%, P < 0.05). Furthermore, the incidence of severe preeclampsia was higher at recurrence in patients with rPE compared to their first onset (83.49% vs. 70.64%, P < 0.05), as well as the incidence of severe preeclampsia with chronic hypertension (34.86% vs. 8.26%, P < 0.05). Additionally, the incidence of gestational diabetes and postpartum hemorrhage was higher in patients with rPE compared to their first preeclampsia onset (25.69% vs. 5.50%, P < 0.05; 20.18% vs. 5.83%, P < 0.05). Compared to the first onset of preeclampsia, patients with rPE had an earlier gestational age at delivery (35.42 ± 3.06 weeks vs. 36.60 ± 2.74 weeks, P < 0.05), lower birth weight of neonates (2478.39 ± 828.44 g vs. 2883.71 ± 712.94 g, P < 0.05), and a higher risk of premature birth (67.00% vs. 47.19%, P < 0.05). However, in patients with rPE, the use of LDA delayed the gestational age at delivery, increased the birth weight of the neonate, reduced the premature birth rate, and increased the perinatal survival rate. In conclusion, patients with rPE are at an increased risk of adverse maternal and fetal outcomes. However, the use of LDA during pregnancy effectively improves these outcomes.

OBJECTIVE: To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia.
METHODS: PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords \"preeclampsia\", \"Low Molecular Weight Heparin\", \"LMWH\", \"Heparin, Low Molecular Weight\", \"Dalteparin\", \"Nadroparin\", and \"Tinzaparin\".
METHODS: Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia.
METHODS: Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI).
RESULTS: LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption.
CONCLUSIONS: For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.

BACKGROUND: Preterm birth is a leading cause of perinatal morbidity and mortality. There are significant racial disparities in the rates of preterm delivery in the United States, with Black individuals at disproportionately higher risk than their White counterparts. Although low-dose aspirin is currently under investigation for reducing the rates of preterm delivery, limited data are available on how the use of low-dose aspirin might affect racial and ethnic disparities in the rates of preterm delivery.
OBJECTIVE: Our group and others have shown that low-dose aspirin decreases spontaneous preterm delivery in low-risk parturients. This study aimed to examine whether the relationship between low-dose aspirin and the risk of spontaneous preterm delivery is modified by race and ethnicity.
METHODS: This was a secondary analysis of a randomized clinical trial examining low-dose aspirin for preeclampsia prevention in low-risk nulliparous individuals. The parent trial defined low risk as the absence of preexisting hypertension or other medical comorbidities. Participants received 60-mg aspirin or placebo between 13 and 25 weeks of gestation. Here, multiple pregnancies, fetal anomalies, terminations or abortions at <20 weeks of gestation, and participants with previous miscarriages were excluded. Our exposure, race and ethnicity, was self-reported in the parent trial and categorized as non-Hispanic White, Hispanic, non-Hispanic Black, and other. The primary outcome was spontaneous preterm delivery at <34 weeks of gestation; the secondary outcomes included spontaneous preterm delivery at <37 weeks of gestation and all preterm deliveries at <34 and <37 weeks of gestation. Fit logistic regression models were used to examine how the use of low-dose aspirin modified the relationship between race and ethnicity and preterm delivery, adjusting for confounders. Furthermore, sensitivity analyses were performed to compare the rates of preterm delivery by race and ethnicity.
RESULTS: Of note, 2528 of 3171 parent study participants were included in this analysis. Of the participants, 425 (16.8%) were White, 819 (32.4%) were Hispanic, 1265 (50%) were Black, and 19 (0.8%) were other. The baseline characteristics differed among racial and ethnic groups, including maternal age, body mass index, education level, marital status, tobacco and alcohol use, and pregnancy loss. The rate of spontaneous preterm delivery at <34 weeks of gestation was significantly higher in Black participants (2.8%) than in White (1.2%) and Hispanic (1.2%) participants (P=.04). Logistical regression analysis showed that Black race was no longer an independent risk factor for spontaneous preterm delivery at <34 weeks of gestation when controlling for low-dose aspirin (adjusted odds ratio, 1.71; 95% confidence interval, 0.67-4.40). A similar pattern was found for spontaneous preterm delivery at <37 weeks of gestation and preterm delivery at <34 and <37 weeks of gestation. In our sensitivity analyses, spontaneous preterm delivery at <34 weeks of gestation differed by race and ethnicity in the placebo group (P=.01) but did not differ in the low-dose aspirin group (P=.90).
CONCLUSIONS: The use of low-dose aspirin mitigated racial disparities in spontaneous preterm delivery at <34 weeks of gestation. Additional investigation is warranted to assess the reproducibility of our findings.

Our objective was to evaluate whether pregnancy is prolonged by the use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in the preterm birth rate. Rather than considering a dichotomous outcome (preterm versus term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with the PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, p < 0.01). Newborns of screened subjects had significantly shorter NICU stays but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We conclude that screening with the PreTRM test followed by interventions for screen-positive pregnancies may prolong pregnancy and reduce NICU LOS, but these observations need to be confirmed by additional research.

Low-dose aspirin (LDA) has been shown to reduce the risk of preterm pre-eclampsia and it has been suggested that it should be recommended for all pregnancies. However, some studies have reported an association between LDA and an increased risk of bleeding complications in pregnancy. Our aim was to evaluate the risk of placental abruption and postpartum hemorrhage (PPH) in patients for whom their healthcare provider had recommended prophylactic aspirin.
This multicenter cohort study included 72 598 singleton births at 19 hospitals in the USA, between January 2019 and December 2021. Pregnancies complicated by placenta previa/accreta, birth occurring at less than 24 weeks\' gestation, multiple pregnancy or those with data missing for aspirin recommendation were excluded. Propensity scores were calculated using 20 features spanning sociodemographic factors, medical history, year and hospital providing care. The association between LDA recommendation and placental abruption or PPH was estimated by inverse-probability treatment weighting using the propensity scores.
We included 71 627 pregnancies in the final analysis. Aspirin was recommended to 6677 (9.3%) and was more likely to be recommended for pregnant individuals who were 35 years or older (P < 0.001), had a body mass index of 30 kg/m2 or higher (P < 0.001), had prepregnancy hypertension (P < 0.001) and who had a Cesarean delivery (P < 0.001). Overall, 1.7% of the study cohort (1205 pregnancies) developed preterm pre-eclampsia: 1.3% in the no-aspirin and 5.8% in the aspirin group. After inverse-probability weighting with propensity scores, aspirin was associated with increased risk of placental abruption (adjusted odds ratio (aOR), 1.44 (95% CI, 1.04-2.00)) and PPH (aOR, 1.21 (95% CI, 1.05-1.39)). The aOR translated to a number needed to harm with LDA of 79 (95% CI, 43-330) for PPH and 287 (95% CI, 127-3151) for placental abruption.
LDA recommendation in pregnancy was associated with increased risk for placental abruption and for PPH. Our results support the need for more research into aspirin use and bleeding complications in pregnancy before recommending it beyond the highest-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Previous studies assessed the prognostic effect of aspirin, statins, and metformin in breast cancer (BC) patients, with inconclusive results.
We performed a nationwide population-based cohort study to evaluate if post-diagnostic use of low-dose aspirin, statins, and metformin was associated with BC-specific survival. Women aged ≥ 50 years and diagnosed with BC in 2004-2017, who survived ≥ 12 months after diagnosis (follow-up started 12 months after diagnosis), were identified in the Cancer Registry of Norway. The Norwegian Prescription Database provided information on prescriptions. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between post-diagnostic use and BC-specific survival, overall and by oestrogen receptor (ER) status.
A total of 26,190 patients were included. Of these, 5324 (20%), 7591 (29%), and 1495 (6%) were post-diagnostic users of low-dose aspirin, statins, and metformin, respectively. The median follow-up was 6.1 years, and 2169 (8%) patients died from BC. HRs for use, compared to no use, were estimated at 0.96 (95% CI 0.85-1.08) for low-dose aspirin (ER+: HR = 0.97, 95% CI 0.83-1.13; ER-: HR = 0.97, 95% CI 0.73-1.29, p value for interaction = 0.562), 0.84 (95% CI 0.75-0.94) for statins (ER+: HR = 0.95, 95% CI 0.82-1.09; ER-: HR = 0.77, 95% CI 0.60-1.00, p value for interaction = 0.259), and 0.70 (95% CI 0.51-0.96) for metformin (compared to use of non-metformin antidiabetics) (ER+: HR = 0.67, 95% CI 0.45-1.01; ER-: HR = 1.62, 95% CI 0.72-3.62, p value for interaction = 0.077).
We found evidence supporting an association between post-diagnostic use of statins and metformin and survival, in patients with BC. Our findings indicate potential differences according to ER status.

UNASSIGNED: It remains controversial whether it is better to continue oral low-dose aspirin (LDA) during the perioperative period in spinal surgery. This study aims to evaluate the safety of continued LDA administration in the perioperative periods of microendoscopic laminectomy (MEL) by assessing perioperative complications and clinical outcomes.
UNASSIGNED: We ultimately included 88 patients (35 males, 53 females) who underwent one level of MEL for lumbar spinal canal stenosis from April 2016 to March 2022. Patients who did not undergo anticoagulation therapy were classified into Group A (65 patients), those who stopped anticoagulation therapy at the perioperative periods were classified into Group B (9 patients), and those who continued oral administration of LDA throughout the perioperative periods were classified into Group C (14 patients). Surgery time, intraoperative estimate blood loss (EBL), differences between hemoglobin (Hb) and platelet (Plt) before and after surgery, perioperative complications, and cross-sectional area of hematoma and dural sac on MRI taken within 1 week and at 6 months or more after surgery were assessed between three groups. The EuroQol-5 dimensions (EQ-5D), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were also evaluated as the clinical outcomes.
UNASSIGNED: There was no statistically significant difference between the three groups in operation time, intraoperative EBL, differences between Hb and Plt before and after surgery, and cross-sectional area of hematoma and dural sac on MRI. A case of hematoma removal was confirmed in Group A. There was also no statistically significant difference between the three groups in EQ-5D, ODI, and each domain of JOABPEQ.
UNASSIGNED: The continuation of LDA throughout the perioperative periods did not affect perioperative complications and clinical outcomes of one-level MEL. In MEL, it might be possible to continue oral administration of LDA throughout the perioperative periods.