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Cureus May 2024Sublingual hematoma, a rare but potentially life-threatening condition, can arise spontaneously or secondary to various triggers, including trauma, dental procedures, or...
Sublingual hematoma, a rare but potentially life-threatening condition, can arise spontaneously or secondary to various triggers, including trauma, dental procedures, or anticoagulant therapy. We present a case of massive spontaneous sublingual hematoma in a 45-year-old woman receiving aspirin therapy for rheumatic heart disease. Despite the absence of trauma or procedural triggers, the patient presented with bleeding from the floor of the mouth and significant submental swelling, prompting urgent intervention to secure the airway and manage coagulopathy. Conservative measures, including discontinuation of aspirin and intravenous vitamin K administration, led to gradual hematoma resolution and favorable patient outcomes. This case highlights the importance of prompt recognition and early management of sublingual hematoma, particularly in the context of aspirin therapy-induced coagulopathy.
PubMed: 38899276
DOI: 10.7759/cureus.60684 -
Cureus May 2024Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in...
Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.
PubMed: 38899239
DOI: 10.7759/cureus.60659 -
Kidney International Reports Jun 2024Beta-carotene (BC) protects the body against free radicals that may damage the kidney and lead to the development of acute kidney injury and chronic kidney disease...
INTRODUCTION
Beta-carotene (BC) protects the body against free radicals that may damage the kidney and lead to the development of acute kidney injury and chronic kidney disease (CKD). Previous studies in animal models have demonstrated a potential protective effect of 30 mg/kg BC supplementation on renal ischemia or reperfusion injury and subsequently improved kidney function. The extension of these findings to humans, however, remains unclear.
METHODS
Our study leverages previously collected data from the Physicians' Health Study I (PHS I), a large-scale, long-term, randomized trial of middle-aged and older US male physicians testing 50 mg BC every other day for primary prevention of cardiovascular disease and cancer. We examined the impact of randomized BC supplementation on self-reported incident CKD identified by self-reports stating "yes" to kidney disease from annual follow-up questionnaires from randomization in 1982 through the end of the randomized BC intervention at the end of 1995, and on CKD defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m at the end of 1995. Analyses compared incident CKD between BC supplementation and placebo using Cox proportional hazards regression models and logistic regression. We also examined whether smoking status (current vs. former or never smoker) or other factors modified the effect of randomized BC supplementation on CKD.
RESULTS
A total of 10,966 participants were randomized to BC, and 10,952 participants were randomized to a placebo group. Baseline characteristics between randomized BC groups were similar. There was no significant benefit between BC supplementation and self-reported incident CKD after adjusting for age and randomized aspirin treatment (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.86-1.08, -value = 0.56). Stratified by smoking status, there was no significant benefit of BC supplementation and self-reported incident CKD either among former or never smokers (HR = 0.95, 95% CI: 0.84-1.07, -value = 0.41) or current smokers (HR = 1.08, 95% CI: 0.78-1.50, -value = 0.64). Smoking status did not modify the association between BC supplementation and incident CKD (-interaction = 0.47). In subgroup analysis among those with available serum creatinine at the study end (5480 with BC and 5496 with placebo), there was no significant benefit between BC supplementation and CKD based on eGFR < 60 ml/min per 1.73 m (odds ratio [OR] = 0.96, 95% CI: 0.85-1.08, -value = 0.49).
CONCLUSION
Long-term randomized BC supplementation did not affect the risk of incident CKD in middle-aged and older male physicians.
PubMed: 38899218
DOI: 10.1016/j.ekir.2024.04.001 -
Biochemical Genetics Jun 2024Osteoporosis, in which bones become fragile owing to low bone density and impaired bone mass, is a global public health concern. Bone mineral density (BMD) has been...
Osteoporosis, in which bones become fragile owing to low bone density and impaired bone mass, is a global public health concern. Bone mineral density (BMD) has been extensively evaluated for the diagnosis of low bone mass and osteoporosis. Circulating monocytes play an indispensable role in bone destruction and remodeling. This work proposed a machine learning-based framework to investigate the impact of circulating monocyte-associated genes on bone loss in osteoporosis patients. Females with discordant BMD levels were included in the GSE56815, GSE7158, GSE7429, and GSE62402 datasets. Circulating monocyte types were quantified via CIBERSORT, with subsequent selection of plasma cell-associated DEGs. Generalized linear models, random forests, extreme gradient boosting (XGB), and support vector machines were adopted for feature selection. Artificial neural networks and nomograms were subsequently constructed for osteoporosis diagnosis, and the molecular machinery underlying the identified genes was explored. SVM outperformed the other tuned models; thus, the expression of several genes (DEFA4, HLA-DPB1, LCN2, HP, and GAS7) associated with osteoporosis were determined. ANNs and nomograms were proposed to robustly distinguish low and high BMDs and estimate the risk of osteoporosis. Clozapine, aspirin, pyridoxine, etc. were identified as possible treatment agents. The expression of these genes is extensively posttranscriptionally regulated by miRNAs and mA modifications. Additionally, they participate in modulating key signaling pathways, e.g., autophagy. The machine learning framework based on plasma cell-associated feature genes has the potential for estimating personalized risk stratification and treatment vulnerability in osteoporosis patients.
PubMed: 38898268
DOI: 10.1007/s10528-024-10861-y -
Scientific Reports Jun 2024The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight... (Meta-Analysis)
Meta-Analysis
The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).
Topics: Humans; Abortion, Habitual; Heparin, Low-Molecular-Weight; Female; Pregnancy; Aspirin; Anticoagulants; Randomized Controlled Trials as Topic; Live Birth
PubMed: 38898143
DOI: 10.1038/s41598-024-62949-5 -
Journal of Bone and Mineral Research :... Jun 2024In previous studies, we have demonstrated that stress response-induced high glucocorticoid levels could be the underlying cause of traumatic heterotopic ossification...
In previous studies, we have demonstrated that stress response-induced high glucocorticoid levels could be the underlying cause of traumatic heterotopic ossification (HO), and we have developed a glucocorticoid-induced ectopic mineralization (EM) mouse model by systemic administration of a high dose of dexamethasone (DEX) to animals with muscle injury induced by cardiotoxin injection. In this model, dystrophic calcification (DC) developed into HO in a cell autonomous manner. However, it is not clear how DC is formed after DEX treatment. Therefore, in this study, we aimed to explore how glucocorticoids initiate muscle EM at a cellular and molecular level. We showed that DEX treatment inhibited inflammatory cell infiltration into injured muscle but inflammatory cytokine production in the muscle was significantly increased, suggesting that other non-inflammatory muscle cell types may regulate the inflammatory response and the muscle repair process. Accompanying this phenotype, transforming growth factor β1 (TGF-β1) expression in fibro-adipogenic progenitors (FAPs) was greatly down-regulated. Since TGF-β1 is a strong immune suppressor and FAP's regulatory role has a large impact on muscle repair, we hypothesized that down-regulation of TGF-β1 in FAPs after DEX treatment resulted in this hyperinflammatory state and subsequent failed muscle repair and EM formation. To test our hypothesis, we utilized a transgenic mouse model to specifically knock out Tgfb1 gene in PDGFRα positive FAPs to investigate if the transgenic mice could recapitulate the phenotype that was induced by DEX treatment. Our results showed that the transgenic mice completely phenocopied this hyperinflammatory state and spontaneously developed EM following muscle injury. On the contrary, therapeutics that enhanced TGF-β1 signaling in FAPs inhibited the inflammatory response and attenuated muscle EM. In summary, these results indicate that FAPs-derived TGF-β1 is a key molecule in regulating muscle inflammatory response and subsequent EM, and that glucocorticoids exert their effect via down-regulating TGF-β1 in FAPs.
PubMed: 38896028
DOI: 10.1093/jbmr/zjae097 -
The Neurohospitalist Jul 2024Dual antiplatelet therapy is often required for neurointerventional procedures, especially when a stent or flow diverter is placed in the cervical and intracranial...
BACKGROUND
Dual antiplatelet therapy is often required for neurointerventional procedures, especially when a stent or flow diverter is placed in the cervical and intracranial vessels. Patients are usually started on aspirin and clopidogrel given the simplicity of the once daily regimen with reasonable cost. Unfortunately, about a third of patients do not show the desired antiplatelet response to clopidogrel and another agent needs to be introduced. Ticagrelor is a potent antiplatelet medication that has a favorable pharmacological profile and has emerged as a reliable alternative to clopidogrel in recent years. Despite ticagrelor non-responders being rare, they do exist, and identification of these patients is important.
RESULTS
A 74-year-old female was incidentally found to harbor a right posterior communicating aneurysm which was successfully treated electively with stent-assisted coiling. Platelet inhibition testing revealed non-responsiveness to Clopidogrel. Ticagrelor was initiated but the patient's platelet reactivity unit remained in the normal range. Management algorithms to maximize a patient's ticagrelor response by facilitating enteral absorption were applied but no platelet inhibition was achieved. The patient was eventually identified as a true ticagrelor non-responder.
CONCLUSION
Resistance to antiplatelet medication can result in devastating complications with permanent neurological deficits. Ticagrelor non-responders are rare but do exist. Platelet inhibition testing should be part of the preprocedural workup for neurointerventions.
PubMed: 38894997
DOI: 10.1177/19418744241228630 -
Journal of Clinical Medicine Jun 2024Management of intracranial aneurysms (IAs) is determined by patient age, risk of rupture, and comorbid conditions. While endovascular and microsurgical interventions... (Review)
Review
Management of intracranial aneurysms (IAs) is determined by patient age, risk of rupture, and comorbid conditions. While endovascular and microsurgical interventions offer solutions to mitigate the risk of rupture, pharmacological management strategies may complement these approaches or serve as alternatives in appropriate cases. The pathophysiology of IAs allows for the targeting of inflammation to prevent the development and rupture of IAs. The aim of this review is to provide an updated summary of different pharmaceutical management strategies for IAs. Acetylsalicylic acid and renin-angiotensin-aldosterone system (RAAS) inhibitor antihypertensives have some evidence supporting their protective effect. Studies of selective cyclooxygenase-2 (COX-2) inhibitors, statins, ADP inhibitors, and other metabolism-affecting drugs have demonstrated inconclusive findings regarding their association with aneurysm growth or rupture. In this manuscript, we highlight the evidence supporting each drug's effectiveness.
PubMed: 38893035
DOI: 10.3390/jcm13113324 -
Journal of Clinical Medicine May 2024Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between... (Review)
Review
Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between 2006 and 2016, the burden of CVD remains disproportionately higher in low- and middle-income countries compared to high-income countries. Even though proven, effective approaches based on multiple-drug intake aimed at the prevention and treatment of CVD are currently available, poor adherence, early discontinuation of treatment, and suboptimal daily execution of the prescribed therapeutic regimes give rise to shortfalls in drug exposure, leading to high variability in the responses to the prescribed medications. Wald and Law, in their landmark paper published in BMJ 2003, hypothesized that the use of a fixed-dose combination of statins, β-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin (classic Polypill composition) may increase adherence and decrease CVD by up to 80% when prescribed as primary prevention or in substitution of traditional protocols. Since then, many clinical trials have tested this hypothesis, with comparable results. This review aims to describe the available clinical trials performed to assess the impact of fixed-dose combinations on adherence, cost-effectiveness, and the risk factors critical to the onset of CVD.
PubMed: 38892892
DOI: 10.3390/jcm13113179 -
Journal of Clinical Medicine May 2024Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic... (Review)
Review
Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-β2-glycoprotein I (β2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.
PubMed: 38892776
DOI: 10.3390/jcm13113064