Vascular Disease Research Articles

Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA Adverse Event Reporting System

ABSTRACT Background The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It’s necessary to investigate the adverse effects (AEs) of these inhibitors. Research design and methods We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). Results Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib. Conclusions The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.

Clinical and patient reported treatment outcomes of livedoid vasculopathy: A systematic review

Abstract Livedoid vasculopathy (LV) is a rare condition affecting the lower extremities, often linked to hypercoagulable states or vascular disorders, and despite increasing treatment options, patients frequently experience suboptimal outcomes. Our systematic review of 44 studies, involving 216 patients, found that Rivaroxaban was the most common treatment, with complete (n=18, 31%) or partial (n=40, 68%) ulcer healing and complete pain resolution in the 19% reported, while IVIG also showed promise, though results were mixed. The review highlights the need for further research to identify optimal treatments for LV and establish a standard of care for future clinical trials.

Neuroma morphology: A macroscopic classification system.

Neuromas come in different shapes and sizes; yet the correlation between neuroma morphology and symptomatology is unknown. Therefore, we aim to investigate macroscopic traits of excised human neuromas and assess the validity of a morphological classification system and its potential clinical implications. End-neuroma specimens were collected from prospectively enrolled patients undergoing symptomatic neuroma surgery. Protocolized images of the specimens were obtained intraoperatively. Pain data (Numeric rating scale, 0-10) were prospectively collected during preoperative interview, patient demographic and comorbidity factors were collected from chart review. A morphological classification is proposed, and the inter-rater reliability (IRR) was assessed. Distribution of neuroma morphology with patient factors, was described. Forty-five terminal neuroma specimens from 27 patients were included. Residual limb patients comprised 93% of the population, of which 2 were upper (8.0%) and 23 (92.0%) were lower extremity residual limb patients. The proposed morphological classification, consisting of three groups (bulbous, fusiform, atypical), demonstrated a strong IRR (Cohen's kappa = 0.8). Atypical neuromas demonstrated higher preoperative pain, compared with bulbous and fusiform. Atypical morphology was more prevalent in patients with diabetes and peripheral vascular disease. A validated morphological classification of neuroma is introduced. These findings may assist surgeons and researchers with better understanding of symptomatic neuroma development and their clinical implications. The potential relationship of neuroma morphology with the vascular and metabolic microenvironment requires further investigation.

Mobilization of Endogenous CD34+/CD133+ Endothelial Progenitor Cells by Enhanced External Counter Pulsation for Treatment of Refractory Angina

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counterpulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injection. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (β = −2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases.

Comorbidity and Disease Activity in Multiple Sclerosis.

Multiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists. To evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS. A 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024. Comorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders. The main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging. A total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14). In this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.

G6pdN126D Variant Increases the Risk of Developing VEGFR (Vascular Endothelial Growth Factor Receptor) Blocker-Induced Pulmonary Vascular Disease.

G6PD (glucose-6-phosphate-dehydrogenase) is a key enzyme in the glycolytic pathway and has been implicated in the pathogenesis of cancer and pulmonary hypertension-associated vascular remodeling. Here, we investigated the role of an X-linked G6pd mutation (N126D polymorphism), which is known to increase the risk of cardiovascular disease in individuals from sub-Saharan Africa and many others with African ancestry, in the pathogenesis of pulmonary hypertension induced by a vascular endothelial cell growth factor receptor blocker used for treating cancer. CRISPR-Cas9 genome editing was used to generate the G6pd variant (N126D; G6pdN126D) in rats. A single dose of the vascular endothelial cell growth factor receptor blocker sugen-5416 (SU; 20 mg/kg in DMSO), which is currently in a Phase 2/3 clinical trial for cancer treatment, was subcutaneously injected into G6pdN126D rats and their wild-type littermates. After 8 weeks of normoxic conditions, right ventricular pressure and hypertrophy, pulmonary artery remodeling, the metabolic profile, and cytokine expression were assessed. Right ventricular pressure and pulmonary arterial wall thickness were increased in G6PDN126D+SU/normoxic rats. Simultaneously, levels of oxidized glutathione, inositol triphosphate, and intracellular Ca2+ were increased in the lungs of G6PDN126D+SU/normoxic rats, whereas nitric oxide was decreased. Also increased in G6PDN126D+SU/normoxic rats were pulmonary levels of plasminogen activator inhibitor-1, thrombin-antithrombin complex, and expression of proinflammatory cytokines CCL3 (chemokine [C-C motif] ligand), CCL5, and CCL7. Our results suggest G6PDN126D increases inositol triphosphate-Ca2+ signaling, inflammation, thrombosis, and hypertrophic pulmonary artery remodeling in SU-treated rats. This suggests an increased risk of vascular endothelial cell growth factor receptor blocker-induced pulmonary hypertension in those carrying this G6PD variant.

Intelligent cardiovascular disease diagnosis using deep learning enhanced neural network with ant colony optimization

To identify patterns in big medical datasets and use Deep Learning and Machine Learning (ML) to reliably diagnose Cardio Vascular Disease (CVD), researchers are currently delving deeply into these fields. Training on large datasets and producing highly accurate validation results is exceedingly difficult. Furthermore, early and precise diagnosis is necessary due to the increased global prevalence of cardiovascular disease (CVD). However, the increasing complexity of healthcare datasets makes it challenging to detect feature connections and produce precise predictions. To address these issues, the Intelligent Cardiovascular Disease Diagnosis based on Ant Colony Optimisation with Enhanced Deep Learning (ICVD-ACOEDL) model was developed. This model employs feature selection (FS) and hyperparameter optimization to diagnose CVD. Applying a min–max scaler, medical data is first consistently prepared. The key feature that sets ICVD-ACOEDL apart is the use of Ant Colony Optimisation (ACO) to select an optimal feature subset, which in turn helps to upgrade the performance of the ensuring deep learning enhanced neural network (DLENN) classifier. The model reforms the hyperparameters of DLENN for CVD classification using Bayesian optimization. Comprehensive evaluations on benchmark medical datasets show that ICVD-ACOEDL exceeds existing techniques, indicating that it could have a significant impact on CVD diagnosis. The model furnishes a workable way to increase CVD classification efficiency and accuracy in real-world medical situations by incorporating ACO for feature selection, min–max scaling for data pre-processing, and Bayesian optimization for hyperparameter tweaking.

Potential of Sulodexide in the Treatment of Diabetic Retinopathy and Retinal Vein Occlusion.

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.

White coat hypertension in acute retinal vein occlusion

PurposeTo investigate the association between white-coat hypertension (WCH) and acute retinal vein occlusion (RVO).MethodsIn this retrospective case-control study, patients aged 40 years or older diagnosed with acute-phase RVO were included. Patients with other pathologies served as non-RVO controls. Blood pressure (BP) was measured in the office during their initial visit, and information about home BP and hypertension (HTN) medication was obtained through interviews. After 1:2 age and sex-matching between the RVO and non-RVO groups, the proportions of HTN cases were compared. A similar comparison was made in subgroups with or without HTN medication.ResultsFifty-one patients with RVO and 102 with non-RVO were included in the analysis. For the entire cohort, the RVO group exhibited a significantly greater proportion of WCH and sustained HTN compared to the non-RVO group. In the subgroup without HTN treatment, the proportion of WCH or sustained HTN was still significantly higher in the RVO group. However, in the subgroup receiving HTN treatment, the proportion of WCH or sustained HTN was higher in the RVO group than in the non-RVO group, though not statistically significant.ConclusionThis case-control study suggests that WCH may be associated with RVO, particularly in patients without HTN treatment. Given that interventions for WCH have not been standardized, a more detailed and prospective study is warranted to elucidate the risk of WCH for RVO and other retinal vascular diseases.

Does having a patient attend a postpartum vascular risk reduction clinic improve physician knowledge and management of preeclampsia as a cardiovascular risk factor?

Background Preeclampsia is an independent risk factor for vascular diseases. The Postpartum Preeclampsia Clinic (PPPC) intervenes in the first year postpartum to address these risks. This study aims to characterize physicians’ understanding and management of the cardiovascular risk associated with preeclampsia and whether this differs in physicians who had a patient attend the PPPC. Methods Family physicians, obstetricians, internists, obstetric internists, and cardiologists in Edmonton were anonymously surveyed. Results were analyzed using SPSS. Results Sixty-four surveys were returned, with physicians correctly identifying preeclampsia as a vascular risk factor 73% of the time. Physicians who had a patient attend the PPPC were more likely to counsel patients on their increased cardiovascular risk, although increased knowledge did not reach statistical significance. Conclusion Vascular risk reduction clinics may benefit the long-term management of patients with a history of preeclampsia by improving counseling by physicians, which may reduce the disproportionate vascular morbidity these patients face.

Derivation of Splenic Stiffness in Subjects with Normal Liver Stiffness and No Vascular Liver Disease Using Transient Elastography with a Spleen-Dedicated Module: A Large Cross Sectional Study.

Liver and splenic stiffness measurements (LSM and SSM) are useful to predict varices and clinical decompensation in cirrhosis. SSM values are highly variable and overlapping and no guidelines exists on what constitutes normal SSM, that might limit interpretation of results. Consecutive subjects with LSM < 6 kPa and reliable SSM (FibroScan630 Expert device with spleen-dedicated module) and no vascular liver disease were analysed for significant correlations of SSM values with age, sex, BMI, portal and splenic vein diameter, splenic diameter, liver fat and diabetes. Based on timeline of SSM, subjects were randomly assigned in 70:30 ratio into derivation [n = 502] and validation subset [n = 214]. Of 7200 subjects with simultaneous reliable LSM and SSM, 715 fulfilled the selection criteria (mean age: 43.8 ± 12.8years, 67.2% male, mean BMI-26.4 ± 4.5kg/m2). The mean SSM was 22.6 ± 5.8kPa (c10-c90 percentile range: 15.2-31.3kPa) and followed the normal distribution curve. In the derivation subset, mean SSM for males was higher than female (23.06 ± 6.2vs. 21.78 ± 5.93kPa; p = 0.028). SSM value correlated with LSM (r = 0.454, p = 0.001). Mean SSM in subjects with LSM 3-4, 4.1-5 and 5.1-6kPa were 21.7 ± 5.8, 22.27 ± 5.67and 23.76 ± 5.88kPa (p value = 0.001). There was no difference in SSM based on age, BMI, diabetes and liver fat on ultrasound. Above results hold true for subjects in validation subset. SSM range in subjects with normal LSM and no vascular liver disease using spleen-dedicated module varies from 15.2 to 31.3kPa, values being higher in male and not affected by Age, BMI, spleen size, liver fat and diabetes. Our results may serve as reference point in evaluation of SSM in compensated advanced liver disease patients.

Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area.

Biomarkers of Oxidative Stress in Diabetic Microvascular Complications Review Article

Reactive oxygen species (ROS) are produced as a result of biochemical processes that are not in balance with the body's antioxidant defense mechanism. This metabolic dysfunction is referred to the oxidative stress (OS). Metabolic dysfunction-associated diseases are affected by changes in the redox balance. It is now widely recognized that oxidative stress significantly affects diabetes mellitus (DM), particularly type 2 diabetes. The biochemical changes associated with DM could disturb the oxidative milieu, leading to several microvascular complications in diabetic patients. Thus, DM is a perfect disease to explore the harmful consequences of oxidative stress and how to treat it. Oxidative stress triggered by hyperglycemia is an important contributor to the effects of diabetic microvascular diseases. Uncontrolled hyperglycemia carried by deficiencies in insulin secretion or action produces a number of problems, such as peripheral vascular disorders, nephropathy, neuropathy, retinopathy, increased morbidity and/or mortality, as well as the incidence of diabetes mellitus (DM) are rising globally. The development and progression of diabetic problems are strongly correlated with reactive oxygen species and oxidative stress, according to a wide body of research. This review aims to explore various markers of oxidative stress and the role of ROS in the pathogenesis and progression of late diabetic microvascular complications.

THE ANTICOAGULATION STRATEGIES FOR MANAGEMENT AND PREVENTION OF STROKE IN NEUROLOGICAL PRACTICE

Strokes are categorized as either ischemic or hemorrhagic and the specific interventions will be based on the type of stroke. About 13% of stroke is hemorrhagic and 87% is ischemic. Transient Ischemic Attacks require emergency intervention to decrease the threat of stroke, which is thought to be maximum within the first few days after TIA. Anticoagulants play a major role in the primary and secondary prevention of ischemic strokes. The optimal timing of anticoagulants initiation or resumption inpreventing and managing ischemic strokes is very important. This article will explore certain controversies surrounding this issue, while also highlighting the benefits of antithrombotic therapy used in prevention of ischemic strokes in antiphospholipid antibody syndrome (APS), atrial fibrillation, prosthetic heart valve, cancer, and vascular disorders. Aggressive local and regional efforts to organize stroke care and greater use of evidence-based recommendations may help improve outcomes. Peer Review History: Received 16 May 2024; Reviewed 11 July 2024; Accepted 24 August; Available online 15 September 2024 Academic Editor: Essam Mohamed Eissa, Beni-Suef University, Egypt, dressamceutics@yahoo.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Taha A.I. El Bassossy, Medicinal and Aromatic Plants Department, Desert Research Center, Cairo, Egypt, tahachemist2008@gmail.com Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, sansan4240732@163.com

Trends in the Treatment of Chronic Wounds.

Chronic wounds remain one of the significant burdens to health across the world, mainly in view of diabetes and its natural consequences. This category of lesions includes pressure ulcers, vascular diseases, and surgery-related wounds, which affect millions and pose a major challenge to the healthcare industry. The paper reviews the various physiological mechanisms of wound healing, factors that impede it, and some new treatments emerging at this moment. In contrast, current developments include surgical and non-surgical alternatives like topical dressings, medicated formulations, and skin substitutes. Advanced wound care today covers tissue-engineered skin substitutes, 3D-printed wound dressings, topical medicated formulations, and growth factor-based therapies. These are non-invasive, biocompatible methods that are cost-effective, userfriendly, and more conducive to natural healing than traditional therapies. Hydrogel dressings have high water content to create a moist environment that encourages healing. They also reflect excellent physicochemical and biological properties, which enhance autolytic debridement and reduction of pain due to the moisture retention, biocompatibility, and non-toxicity conferred. Tissue-engineered skin substitutes, comprising allogeneic or autologous cells, wound-healing enhancement bioengineered allogeneic cellular therapies are like the natural skin and encourage regeneration. 3D printing allows the production of customized dressings to aid in better treatment. Newer therapies, including bioengineered allogeneic cellular therapies and fish skin grafting, require more clinical trials to confirm safety and efficacy. With such innovations in wound healing technologies and therapies, the future looks quite promising in managing chronic wounds, enhancing healing, reducing healthcare expenditure, and promoting a better quality of life for patients.

The Effects of Diabetes on Gas Transfer Capacity, Lung Volumes, Muscle Strength, and Cardio-pulmonary Responses During Exercise.

Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known. Research question Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity? Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories. 40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27kg/m2). The presence of diabetes was independently associated with a reduction in FEV1 (-130ml), FVC (-220ml), DLCO (-1.52ml/min/mmHg), and VA (-340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), p < 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI. The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI.

Establishment of Mouse Models of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a chronic vascular disease that commonly affects elderly individuals but has recently increased in younger populations. As the aneurysm grows, it can cause compression symptoms such as abdominal pain, rupture, and bleeding, which are absent in the early stages. Once an AAA ruptures and causes bleeding, the mortality rate is alarmingly high. Currently, the pathogenesis for AAA is unknown, and therapeutic options are limited, necessitating improvement in treatment efficacy. An essential research method for studying the processes and potential treatment of AAA is establishing animal models using mice. The present study provides a detailed overview of the widely used AAA mouse animal models and their construction strategies, advantages, disadvantages, scope of applications, and prospects.

Phenogroups and Their Prognosis of Acute Decompensated Heart Failure with Preserved Ejection Fraction.

Acute heart failure is an important cause of unplanned hospitalizations and poses a significant burden through increased mortality and frequent hospitalizations. Heart failure with preserved ejection fraction (HFpEF) presents as a diverse condition characterized by complex cardiovascular and non-cardiovascular pathology. This study aimed to identify distinct clinical phenotypes in acute decompensated HFpEF (ADHF) using cluster analysis and assess their prognostic significance. We applied a latent class analysis to 1,281 ADHF patients admitted to a single cardiac intensive care unit between 2008 and 2022 with a left ventricular ejection fraction ≥ 50%. We used 83 factors obtained at hospitalization. We evaluated the association between phenogroups and clinical outcomes using either Cox regression model or Fine-Gray competing risk model. We identified 4 phenogroups: Phenogroup 1 (n = 133, 10%) included younger patients with metabolic disorders and a low level of B-type natriuretic peptide (BNP); Phenogroup 2 (n = 346, 27%) had systemic congestion and high BNP levels; Phenogroup 3 (n = 514, 40%) had multiple comorbidities and vascular disorders; Phenogroup 4 (n = 288, 22%) included older patients with bradyarrhythmia and atrial fibrillation. After adjusting for age, sex, and Get with the Guidelines-Heart Failure risk score, Phenogroup 2 had the highest risk of all-cause death and cardiac death. In conclusion, we identified 4 clinically relevant phenogroups of ADHF patients, each associated with different adverse outcomes. Phenotyping may provide a better understanding of the underlying mechanisms involved in the heterogeneity of ADHF and decompensation. Furthermore, it may facilitate the search for phenotype-specific therapeutic strategies.

Safety analysis of fluoroquinolone drugs in elderly patients over 65 based on FAERS

ABSTRACT Objective This study investigates adverse drug event (ADE) reports from the FAERS related to FQs drugs (ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin) in patients aged 65 and older. The findings aim to guide the rational clinical use of these drugs in elderly patients. Methods We employed Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for the representative FQ drugs from Q1 2015 to Q4 2023, covering 36 quarters. Results The analysis identified 6883 ADE cases for ciprofloxacin, 5866 for levofloxacin, 1498 for moxifloxacin, and 317 for ofloxacin. Moxifloxacin showed higher incidences of Cardiac disorders and Psychiatric disorders ADEs (4.01%, 23.11%).The strongly associated ADEs were Torsade de pointes(X2:255.69),Delirium(X2:4600.04),Dysphoria(X2:11802.38),Mental disorder(X2:3584.69);Vascular disorders ADEs were similar among FQs.Ciprofloxacin and levofloxacin showed higher ADE rates in musculoskeletal and connective tissue diseases (20.18% and 26.97%) compared to moxifloxacin(3.62%) and ofloxacin(9.25%),The most frequently reported and strongly associated ADEs were tendinitis (X2: 13383.57, X2: 31499.01), tendon pain (X2: 18730.22, X2: 40313.79), and tendon disorders (X2: 9534.69, X2: 13143.72).Additionally, moxifloxacin and ofloxacin showed higher ADE rates for eye disorders (10.61% and 15.03%). Significant ADEs included iridocyclitis (X2: 10931.34) and corneal erosion (X2: 1348.35). Conclusion Different FQs exhibit varying ADE profiles across cardiovascular, vascular and lymphatic, renal and urinary, psychiatric, musculoskeletal and connective tissue, and ocular systems. Patients with underlying systemic diseases should avoid FQs with higher ADE risks for their conditions. Enhanced monitoring and evaluation of FQs are crucial for promptly identifying and managing adverse reactions. Personalized medication plans for elderly patients should also be strengthened.

Sensitive Cancer Hypoxia Detection via a Dual-Locking Fluorescence Response System Using Two Hypoxia Indicators.

Hypoxia is intricately associated with various diseases, including ischemia, vascular disorders, and cancer. Particularly in cancer cells, hypoxia promotes tumor growth, cell proliferation, migration, and invasion and enhances treatment resistance, making its detection crucial for cancer diagnosis and therapy. However, methods for detecting hypoxia are limited, often relying on single-detection systems. In this study, we developed a dual-lock-based fluorescent probe that selectively exhibits strong green fluorescence under hypoxic conditions due to simultaneous activity of nitroreductases (NTRs) and hydrogen sulfide (H2S), with a high signal-to-background ratio. The biocompatibility and photophysical properties of the probes were thoroughly investigated through both extracellular and intracellular experimental analyses. Among the synthesized naphthalimide-based probes, the dual-detection probe DNNC demonstrated excellent selectivity and sensitivity to the simultaneous activity of NTR/H2S compared to other single-detection probes. The performance of DNNC was applied to various organ-derived cancer cells and tumor tissue models such as HeLa cell sparoids, enabling spatiotemporal confocal fluorescence imaging and quantitative analysis of hypoxic levels in cancer. Our development of DNNC is expected to significantly advance cancer diagnosis and treatment by molecularly detecting hypoxia associated with cancer aggressiveness, therapy resistance, and unfavorable prognosis.