Search Results (650)

Background: Hereditary angioedema (HAE) is a rare, potentially life-threatening disease in which delayed recognition and inappropriate medication use may result in preventable morbidity and mortality. We aimed to assess physicians’ knowledge regarding HAE-related triggers, clinical features, and management strategies across multiple medical specialties. Methods: This single-center, cross-sectional survey was conducted among 350 physicians at a tertiary training and research hospital. A structured electronic questionnaire assessed knowledge of HAE pathophysiology, diagnosis, medication-related triggers, and management. A predefined composite knowledge score (0–14) was calculated. Results: Although self-reported familiarity with HAE was high, overall disease-specific knowledge was limited. Awareness of critical medication-related triggers—including angiotensin-converting enzyme inhibitors, dipeptidyl peptidase-4 inhibitors, and estrogen-containing therapies—was low across all specialties, with no significant between-group differences. Substantial knowledge gaps were identified in the recognition of clinical features, diagnostic evaluation, and acute management. In multivariable analysis, prior clinical exposure to HAE patients was the only independent predictor of higher knowledge scores (B = 1.097, p = 0.001), whereas specialty group, gender, and years of professional experience were not independently associated with knowledge scores. However, the regression model explained only a small proportion of the variance in knowledge scores. Conclusions: Significant gaps in clinically relevant HAE knowledge persist among physicians from multiple medical specialties. Prior clinical exposure was associated with higher knowledge scores, whereas specialty group, gender, and years of professional experience were not independently associated with physician knowledge. Targeted, practice-oriented educational interventions focusing on medication-related triggers and acute management may help bridge these knowledge gaps, complement experiential learning, and ultimately enhance patient safety. Full article

Background/Objectives: The global rise in obesity-related hypertension, metabolic syndrome, and chronic inflammation calls for a precise characterization of the safety profiles of first-line therapies. While amlodipine is considered metabolically neutral, its real-world impact on dysglycemia and inflammatory biomarkers remains incompletely defined. This study aims to characterize the metabolic and inflammatory adverse drug reaction profile of amlodipine, using the EudraVigilance database. Methods: Descriptive and disproportionality analyses were performed on 41,872 Individual Case Safety Reports recorded prior to 17 May 2026. Amlodipine was compared against major antihypertensive classes (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartans, and diuretics), calculating reporting odds ratios (ROR) and 95% confidence intervals. Results: “Hyperglycaemia” could be considered a safety signal for amlodipine, compared to beta-blockers (e.g., bisoprolol—ROR: 2.56), ACE inhibitors (e.g., ramipril—ROR: 2.82), and sartans (e.g., candesartan—ROR: 3.85). “Metabolic syndrome” was reported for amlodipine with a lower probability than for hydrochlorothiazide (ROR: 0.35). Inflammatory signals (e.g., increased C-reactive protein) appeared less frequently for amlodipine than for certain renin–angiotensin–aldosterone system inhibitors (e.g., perindopril—ROR: 0.53). Conclusions: The disproportionality analysis identified relatively lower reporting frequencies for several metabolic and inflammatory adverse drug reactions, compared with selected antihypertensive agents. These findings represent pharmacovigilance signals that warrant further investigation in analytical epidemiological and clinical studies. Although hyperglycemia was reported disproportionally relative to several comparator drugs, reports of T2DM were less frequently reported for amlodipine. However, these observations should not be interpreted as evidence of differences in clinical risk, because disproportionality analyses cannot establish incidence or causality. Reports of inflammation likely reflect patient comorbidities rather than a direct drug effect. These findings demonstrate that post-marketing surveillance remains essential, even when accounting for the methodological limitations of spontaneous reporting. Full article

Background: Resistant hypertension poses a significant therapeutic challenge, often leading to severe polypharmacy. Renal denervation (RDN) has re-emerged as a valuable adjunctive intervention for blood pressure control. Case Presentation: We report the case of a 64-year-old man (body mass index [BMI] 34 kg/m²) with long-standing resistant hypertension (RH), after previous percutaneous coronary intervention (PCI) to the left anterior descending artery, heart failure with preserved ejection fraction (HFpEF), and prior nephron-sparing surgery for clear cell renal carcinoma. Despite treatment with an extensive antihypertensive regimen encompassing nine pharmacological classes including diuretic therapy (angiotensin-converting enzyme inhibitor; calcium channel blocker, thiazide diuretic, β-blocker, α1-blocker, central α2-agonist, mineralocorticoid receptor antagonist, loop diuretic, long-acting nitrates), blood pressure remained severely uncontrolled on both home and office measurements. Persistent hypertension was accompanied by exertional dyspnoea and episodes of exertional chest discomfort. Following comprehensive evaluation and exclusion of secondary causes of hypertension, the patient underwent catheter-based renal denervation using the SymplicitySpyral™ (Medtronic) multi-electrode radiofrequency system. The procedure was associated with substantial and sustained improvement in blood pressure control, with mean 24 h ambulatory blood pressure measurements decreasing to 130/80 mmHg at six-month follow-up. Importantly, successful blood pressure reduction enabled major simplification of pharmacotherapy, including complete discontinuation of clonidine, loop diuretic therapy, and long-acting nitrates, together with marked dose reduction in doxazosin. Conclusions: This case illustrates the potential clinical utility of renal denervation in carefully selected patients with true resistant hypertension and pronounced sympathetic overactivity. Beyond achieving satisfactory blood pressure control, RDN may facilitate meaningful reduction in medication burden, potentially improving treatment adherence, quality of life, and long-term cardiovascular risk. Written informed consent was obtained from the patient for both the procedure and the publication of this case report. Full article

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in metastatic non-small cell lung cancer (NSCLC), yet only a subset of patients derives durable benefit, suggesting that host and tumor-related factors may modify treatment efficacy. The renin–angiotensin system has been implicated in regulation of the tumor microenvironment, and angiotensin-converting enzyme inhibitors (ACEIs) have therefore been proposed as potential modulators of immunotherapy response. Material and methods: We conducted a retrospective observational cohort study including patients with advanced metastatic NSCLC treated in the first-line setting with treatment-based immunotherapy, with or without chemotherapy, between January 2017 and September 2025. Chronic ACEI exposure was defined as continuous use for at least two years prior to initiation of immunotherapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier estimates and compared using the log-rank test, and multivariable Cox proportional hazards models were adjusted. Results: Among 446 eligible patients, 71 (16%) received ACEIs and 375 (84%) did not. The median age of the cohort was 67.5 years, and 70% were male. Adenocarcinoma was the predominant histology (67.7%), and most patients received chemo–immunotherapy (81.6%), while 18.4% received immunotherapy alone. PD-L1 expression ≥ 1% was present in 59.2% of patients. In the overall cohort, median PFS and OS were 12 and 15 months, respectively. Median OS was 17 months in the ACEI group compared with 14 months in the non-ACEI group (log-rank p < 0.047), while median PFS was 14 months versus 11 months, respectively (p = 0.066). The survival advantage was more pronounced for OS than for PFS and remained consistent after adjustment for clinical characteristics including age, sex, ECOG performance status, smoking status, histology, treatment regimen, and PD-L1 expression. Conclusions: These findings suggest that chronic ACE inhibitor use may be associated with improved outcomes in metastatic NSCLC patients treated with immune checkpoint inhibitors. Full article

Among cardiovascular diseases, myocardial infarction (MI) has become one of the leading causes of mortality worldwide, and the prevalence is anticipated to rise considerably in the coming years. Within non-surgical procedures, chemical drugs, including diuretics, vasodilators, calcium channel blockers, ꞵ blockers, angiotensin converting enzyme inhibitors, are now a well-established option to treat MI progression. However, these drugs are not developed to mitigate oxidative stress directly, which has been recently proven to contribute to MI advancement. Naturally occurring antioxidant compounds possess promising cardioprotective properties and have the potential to be used both as lead compounds for finding novel drugs and complementary therapy to manage MI. While some of them, namely quercetin, puerarin, α-lipoic acid, and curcumin, have already made their way up to clinical trials, numerous compounds have not been sufficiently investigated clinically. To develop and formulate natural antioxidant compounds as drugs against MI, it is crucial to comprehend their underlying mechanisms of cardio-protective activities and structure–activity relationships (SARs). This comprehensive review sheds light on the contribution of oxidative stress in the pathogenesis and progression of Myocardial Infarction, and highlights the cardio-protective roles of 51 natural antioxidant compounds along with their mechanistic insights and SAR. Full article

Background: Migrated foreign bodies in the prevertebral region represent a rare but potentially serious condition. This case underscores the importance of thorough visual and digital intraoperative exploration for successful foreign body retrieval and highlights the potential diagnostic and surgical challenges associated with migrated foreign bodies in the cervical region. Case report: A 77-year-old female patient presented with dysphagia following the intake of an Angiotensin-Converting Enzyme (ACE) inhibitor. Due to hemodynamic instability and laboratory findings that indicated multiple organ failure, a computed tomography (CT) scan was performed, which revealed a left-sided prevertebral abscess with gas collections. Because of persistently elevated and fluctuating inflammatory markers, multiple CT scans were performed, which showed an obliquely oriented, wire-like tubular structure approximately 30 mm in length, 5 mm in width and 1 mm in diameter in the prevertebral region of the previous abscess cavity. Eventually, after three surgical interventions—one transoral and two transcervical approaches—the foreign body could be identified and removed. Afterwards, the patient’s inflammatory markers decreased and her dysphagia resolved. Conclusions: This case demonstrates that early diagnosis and timely removal of foreign bodies in the cervical space are essential to prevent complications such as retropharyngeal abscess formation or mediastinitis. A combination of careful clinical examination, endoscopic evaluation, and cross-sectional imaging—particularly CT scan—is crucial for accurate localization. Finally, this report highlights the importance of maintaining a high index of suspicion for migrated foreign bodies in patients presenting with persistent symptoms or unexplained cervical infections following suspected foreign body ingestion. Full article

The inhibition of angiotensin-converting enzyme (ACE) to lower angiotensin is important in the treatment of hypertension (HT). ACE inhibitory activity is rarely documented in Thai traditional and indigenous medicine. Here, we evaluated the angiotensin I–converting enzyme inhibitory (ACEi) activity through bio-screening of selected medicinal plant species traditionally used for HT treatment by ethnic communities in northern Thailand, including Blumea balsamifera (L.) DC., Clerodendrum chinense (Osbeck) Mabb., Rotheca serrata (L.) Steane & Mabb., and Zingiber purpureum Roscoe. Using an in vitro assay, ethanolic extracts were evaluated for ACE inhibitory activity. Among the four extracts tested, the ethanolic leaf extract of Blumea balsamifera was the most effective by reducing ACE activity by 29, 36, and 64% at concentrations of 0.4, 2.0, and 10.0 mg/mL, respectively. The rhizome extract of Zingiber purpureum showed the second highest activity, with inhibition rates of 34%, 39%, and 40% at the corresponding concentrations. Cytotoxicity testing in HEK293T kidney cells was conducted to underscore the detectable toxicity under the tested conditions. Interestingly, intercultural and cross-cultural comparisons revealed a degree of agreement in the use of medicinal plants for hypertension treatment. Plant species traditionally used across multiple cultures tended to show higher levels of ACE inhibitory activity, suggesting their potential as candidates for the development of novel anti-hypertensive agents. To our knowledge, this is the first report describing the ACE inhibitory activity of medicinal plant species used for hypertension treatment by ethnic communities in northern Thailand. Full article

Background/Objectives: Fibronectin glomerulopathy (FNG) is a rare autosomal dominant inherited kidney disease. Approximately 40% of genetically confirmed FNG cases are associated with likely pathogenic variants in FN1. Patients with FNG have similar clinical features as those with chronic nephritis. Due to nonspecific clinical manifestations mimicking common childhood glomerular diseases, FNG poses significant diagnostic challenges in children, frequently resulting in delayed diagnosis. Case Description: A 9-year-old Chinese girl presented with manifestations suggestive of acute poststreptococcal glomerulonephritis (APSGN), including edema, hypertension, hypocomplementemia, nephrotic-range proteinuria (3.34 g/24 h), and microscopic hematuria (45–55 cells/HP). Despite resolution of edema and normalized complement C3 after initial therapy, proteinuria and hematuria persisted. Renal biopsy revealed prominent mesangial deposits extending to glomerular capillary walls, with strong fibronectin (FN) immunoreactivity and fibrillary electrondense deposits on electron microscopy. Genetic testing identified a heterozygous FN1 missense variant c.3051G>C (p.Trp1017Cys) in the proband and her asymptomatic father, classified as likely pathogenic per ACMG guidelines (supporting evidence: PS1, PM2, PP3, PP4). mRNA and cDNA sequencing confirmed the transcription of the mutant allele in the family members. Notably, these transcriptional analyses cannot provide direct evidence for the functional pathogenicity of the variant. The patient received combined angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy, and renal function remained stable during 3 years of follow-up. Conclusions: The FN1 c.3051G>C represents a novel nucleotide variant, while the corresponding amino acid alteration p.Trp1017Cys has been reported in the previous literature. This case expands the variant spectrum of FN1 and emphasizes the critical value of renal biopsy and genetic testing for diagnosing FNG in pediatric patients with persistent renal manifestations after suspected APSGN. Family screening is essential for identifying asymptomatic carriers. Our findings also highlight the phenotypic heterogeneity of FNG. Full article

Diabetic kidney disease (DKD) represents the single most common etiology of chronic kidney disease and end stage kidney disease globally, a burden that continues to expand in direct proportion to the worldwide growth of the diabetes epidemic. The pathogenesis of DKD is multifactorial, involving metabolic, hemodynamic, inflammatory, and fibrotic pathways. Among these, aldosterone has emerged as a key mediator of kidney injury, extending beyond its traditional role in sodium balance and blood pressure regulation. Through activation of both MR-dependent transcriptional processes and MR-independent signaling cascades, aldosterone drives a coordinated pattern of renal injury encompassing oxidative stress generation, endothelial dysfunction, podocyte damage, inflammatory cell recruitment, and progressive interstitial fibrosis. Current therapies targeting the renin–angiotensin–aldosterone system (RAAS), including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists, have significantly improved outcomes in DKD. Despite these advances, a considerable degree of residual cardiovascular and renal risk persists, attributable in part to the incomplete attenuation of aldosterone activity and the well-characterized phenomenon of aldosterone escape under sustained RAAS blockade. Aldosterone synthase inhibitors (ASIs) represent a mechanistically distinct therapeutic approach that targets aldosterone overproduction at its enzymatic source, potentially addressing both MR-dependent and independent pathways. Early clinical trials evaluating the efficacy of ASIs have demonstrated promising effects on blood pressure and albuminuria. This review summarizes the role of aldosterone in DKD pathogenesis, evaluates current therapeutic approaches, and discusses emerging evidence supporting ASIs as a potential addition to the evolving treatment landscape. Full article

Background/Objectives: Diuretic resistance is a recognized complication in patients with heart failure (HF) and is associated with worse clinical outcomes; however, information regarding its frequency and associated factors in hospitalized patients in Mexico is limited. This study aimed to describe the frequency of diuretic resistance in patients hospitalized with HF in a hospital unit in western Mexico and to identify factors associated with diuretic resistance. Methods: This retrospective study used data obtained from clinical records. Patients older than 18 years with decompensated HF whose complete clinical records included the variables of interest were included. Patients were classified according to the presence or absence of diuretic resistance. Bivariate and multivariate analyses were performed to evaluate factors associated with diuretic resistance. Results: A total of 76 patients were analyzed, and the frequency of diuretic resistance was 35.5% (n = 27). In bivariate analysis, type 2 diabetes mellitus, chronic kidney disease, elevated creatinine, urea, blood urea nitrogen (BUN), and urine protein levels, decreased glomerular filtration rate (GFR) and serum albumin, and prior treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists (ACEI/AARII) were significantly associated with diuretic resistance. In the multivariate logistic regression model, prior ACEI/AARII treatment, history of type 2 diabetes mellitus, BUN levels, and serum albumin levels remained independently associated with diuretic resistance classification. Conclusions: Diuretic resistance was frequent in this cohort of patients hospitalized with decompensated heart failure, and several clinical and biochemical factors were independently associated with its occurrence. These findings may help identify patients at higher risk of diuretic resistance, although they should be confirmed in future prospective studies. Full article

Particularly in regions experiencing rapid industrial and healthcare development, the presence of pharmaceutical residues in wastewater is becoming an increasingly pressing environmental concern. In this study, an analytical method was developed to quantify lisinopril (LIS), ramipril (RAM), and enalapril (ENA) in wastewater while being both sensitive and inexpensive. To improve the precision and accuracy of the measurements, propranolol (PRO) was used as an internal standard. To achieve dual preconcentration and enhanced sensitivity, the method integrates filed amplified sample stacking (FASS) with solid-phase extraction (SPE) before capillary electrophoresis (CE) in a synergistic way. Important experimental factors such the composition of the background electrolyte (BGE), pH, injection settings, stacking efficiency, and selection of the SPE sorbent were meticulously calibrated. Under ideal circumstances, the SPE-CE-FASS method demonstrated remarkable linearity within the concentration range of 10–1000 ng L⁻¹ (R² > 0.999), an outstanding level of accuracy (intra- and inter-day RSD < 6%), and satisfactory recovery percents (90–97%) in real wastewater samples. This method offers an eco-friendly and cost-effective alternative to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) by reducing waste, using less solvent, and providing enough sensitivity for trace-level analysis. Hence, it is very suitable for the regular monitoring of angiotensin converting enzyme (ACE) inhibitors in complex wastewater matrices. Full article

Background: In patients with type 2 diabetes mellitus (T2DM), angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are first-line antihypertensive treatments with important cardiovascular benefits, but their impacts on coronary-specific inflammation are unknown. Pericoronary adipose tissue (PCAT) attenuation, as assessed by coronary computed tomography angiography (CCTA), serves as a specific biomarker for coronary inflammation. Here, we aim to assess whether treatment with ACE-I or ARB is correlated with lower PCAT attenuation. Methods: In this retrospective observational study, we analyzed 223 patients with T2DM and coronary atherosclerosis who underwent CCTA from 1 January 2017 to 1 September 2024 at our institution. PCAT attenuation was measured in the proximal right coronary artery. Propensity score matching and multivariate linear regression analyses were performed for comparisons. Results: Of the 223 patients (mean age of 64.9 ± 8.8 years, 69.1% male), 122 patients were on ACE-I or ARB (ACE-I/ARB). ACE-I/ARB users had similar PCAT attenuation as their counterparts after propensity score matching (−72.1 ± 7.5 and −71.7 ± 8.1 HU, respectively; p = 0.722). Subgroup analysis in patients with glomerular filtration rate (GFR) < 90 mL/min revealed lower PCAT attenuation in ACE-I/ARB users (−74.8 ± 6.6 vs. −71.4 ± 7.1 HU; p = 0.038), with a significant interaction between these two factors in the multivariate analysis (p = 0.047). Other antihypertensive treatments (beta blockers, dihydropyridine calcium channel blockers, and thiazides) were not linked with lower coronary inflammation. Conclusions: In T2DM patients with coronary atherosclerosis, we did not find an association between ACE-I/ARB treatment and lower coronary inflammation as defined by PCAT attenuation, although such a relationship may exist in those with reduced GFRs. Full article

Hypertension remains a leading cause of global morbidity and mortality, and angiotensin-converting enzyme (ACE) represents a central therapeutic target within the renin–angiotensin–aldosterone system. Marine microalgae, particularly Phaeodactylum tricornutum, provide an underexplored reservoir of structurally diverse metabolites with potential cardiovascular relevance. In this in silico study, we characterized metabolites putatively annotated by UPLC-ESI-HRMS and evaluated their predicted ACE inhibitory potential. We performed molecular docking with AutoDock 4 and assessed pharmacokinetic and toxicological properties using the SwissADME, PASS, and ProTox platforms. Several metabolites showed favorable binding orientations within the ACE catalytic pocket, including interactions with key residues and proximity to the zinc-binding motif. Lehualide G, Val–Asn–Pro, tanariflavanone B, hydroxyterbinafine, and anhydro-vitamin A exhibited the most favorable docking profiles. PASS predictions indicated vascular-related bioactivity signals for selected compounds, whereas ADMET modeling revealed heterogeneous but classifiable pharmacokinetic and safety characteristics. The convergence of predicted binding compatibility, bioactivity signals, and stratified safety margins supports P. tricornutum as a promising source of candidate molecules for further experimental validation in antihypertensive research. Full article

Heat waves have intensified since the 1960s, leaving older adults uniquely susceptible to heat-related illnesses, including hyperthermia and fluid-electrolyte imbalances. While clinicians recognize that certain medications increase heat vulnerability, the specific interplay between drug use and patient characteristics remains unclear. This scoping review, following the Joanna Briggs Institute framework for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, investigated the risk of heat-related illness associated with medication use in older adults to identify research gaps. Investigators queried four databases for English-language primary literature (2000–2025) based on predefined Population, Concept, and Context criteria. Additionally, a grey literature search mapped existing United States (U.S.) mitigation strategies. Two reviewers independently screened studies via Covidence, and one extracted data. Results included 61 primary studies and 41 grey literature sources. While epidemiological data confirm higher heat-related morbidity and mortality in older populations, few experimental studies evaluate medication’s specific role. Despite many public health efforts, specific, evidence-based guidance on managing drug-heat interactions is limited. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), anticholinergics, and antipsychotics were the medication classes most frequently associated with heat-related illness. This review underscores a critical need for research into the confluence of age, multimorbidity, and polypharmacy to inform future clinical mitigation and protect vulnerable populations. Full article

Gut microbiome composition influences cardiovascular drug efficacy and safety, yet its integration into heart failure (HF) management remains underexplored. Alterations in intestinal microbial communities have been linked to atherosclerosis, coronary artery disease, heart failure, and hypertension through multiple mechanisms. Dysbiosis disrupts the balance between commensal and pathogenic bacterial species, impairing gut barrier function and activating inflammatory pathways. The altered microbial ecosystem modulates the production of key metabolites—such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acids (BAs)—that directly impact cardiovascular function. This narrative review synthesizes current evidence on bidirectional interaction between heart failure pharmacotherapy and gut microbiome composition. Commonly used drugs in heart failure management show microbiome-dependent pharmacokinetics. Digoxin undergoes bacterial inactivation by Eggerthella lenta, while angiotensin converting enzyme inhibitors and beta-blockers demonstrate enhanced efficacy with specific Firmicutes populations. Conversely, certain probiotic strains attenuate drug-induced gut barrier injury and restore gut homeostasis. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists, and angiotensin receptor–neprilysin inhibitors exhibit beneficial microbiome-modulating effects beyond their primary cardiovascular actions. These findings underscore the potential for microbiome-informed precision medicine in heart failure. However, significant methodological challenges must be addressed, including lack of standardization in microbiome profiling, small sample sizes, and limited longitudinal data. Future research should focus on identifying specific microbial signatures that predict drug response, developing targeted probiotic interventions, and conducting prospective clinical trials to validate pharmacomicrobiomics approaches in heart failure management. Full article