Search Results (9,751)

Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic characteristics, comorbidities, and survival outcomes of patients with AS, stratified by gender and aortic valve morphology. Methods: A retrospective analysis of 145,454 echocardiographic examinations (2009–2018) at the Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” identified 84,851 patients meeting the inclusion criteria (Vmax ≥ 2.0 m/s, age ≥ 18 years). Patients were stratified by gender and valve morphology (bicuspid aortic valve [BAV] vs. tricuspid aortic valve [TAV]). Survival was assessed in 475 pts with AS over a 16-year period (2009–2025) using Kaplan–Meier analysis. Statistical comparisons utilized STATISTICA v. 10.0, with p-values derived from P-tests. Results: Of the cohort, 4998 men and 6322 women had AS. Men with AS were older (median 64 vs. 57 years, p < 0.0001) and had higher systolic blood pressure (140 vs. 130 mmHg, p < 0.0001) than men without AS. Women with AS were also older (median 70 vs. 58 years, p < 0.0001) with higher systolic (140 vs. 130 mmHg, p < 0.0001) and diastolic blood pressure (80 vs. 80 mmHg, p < 0.0001). Men with AS had higher rates of hyperlipidemia (HLP) (26.3% vs. 10.3%, p < 0.0001), while women with AS had increased coronary artery disease (CAD) (35.7% vs. 26.4%, p < 0.0001), diabetes mellitus (DM) (13.4% vs. 10.2%, p < 0.0001), and obesity (10.9% vs. 10.2%, p = 0.06). Chronic heart failure (CHF) was more frequently reported in patients with AS, regardless of gender, compared to patients without AS (in men 53.4% vs. 41.8%, p < 0.0001; in women 54.5% vs. 37.5%, p < 0.0001). BAV was associated with higher AS prevalence (54.5% in men, 66.4% in women). Survival analysis revealed higher mortality. Over the 16-year follow-up period, the mortality rate was 21.7%. Conclusions: Mortality in a representative AS cohort reached 21.7%, underscoring the progressive nature of the disease and its long-term impact. Survival was negatively affected by age over 68.5 years, as well as the presence of aortic regurgitation (AR), increased peak aortic jet velocity, and enlarged maximum aortic diameter. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. Beta-blocker therapy in patients with varying degrees of aortic AS severity has not only demonstrated its safety but has also shown a positive effect on reducing mortality (improving survival). In contrast, the combination of angiotensin II receptor blockers (ARBs) with calcium channel blockers (CCBs) is quite dangerous for patients with AS and reduces their survival. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. In contrast, the absence of fibrinolytic therapy and anticoagulant treatment is associated with an improved prognosis. Conversely, the administration of antiarrhythmic agents and statins is correlated with enhanced survival outcomes, potentially attributable to their influence on coexisting comorbidities. Further research is required to delineate their precise mechanisms and contributions. These results emphasize the importance of early identification, comprehensive risk assessment, and individualized management strategies in improving outcomes for patients with AS. Full article

Background: Conservative mastectomy with prepectoral breast reconstruction is becoming increasingly widespread and validated in recent years. Today, while aesthetic advantages and improvement in quality-of-life outcomes are widely acknowledged, oncological safety remains subject of debate. There is limited evidence on residual breast tissue after conservative mastectomy, and it still represents an unknown risk for local recurrence. The recent spread of this surgical technique precludes a standardized surgical approach in case of local recurrence of ipsilateral breast cancer, and the lack of evidence in the literature complicates the decision-making process. The objective of this study is to describe the surgical treatment of local relapses for breast cancer patients following conservative mastectomy and prepectoral implant-based reconstruction. Methods: Between January 2018 and May 2024 at a single institution, 648 consecutive patients underwent conservative mastectomy and prepectoral reconstruction as their primary treatment. We identified 12 patients with T1-2 breast cancer who subsequently had histologically confirmed ipsilateral breast cancer recurrence and a local wide excision or radical mastectomy were performed. Each clinical case was discussed in a multidisciplinary meeting to define the most appropriate surgical treatment. At time of diagnosis of recurrence, patients with lymph node metastasis or systemic involvement were excluded from the study. Results: Among 648 consecutive patients who underwent conservative mastectomy, 12 with histologically confirmed ipsilateral breast cancer recurrence were included. The mean interval to recurrence was 43 months (range 10–76 months) from the primary operation. Recurrence sites were as follows: upper outer quadrant in four patients (33.4%), upper inner quadrant in three (25.0%), lower inner quadrant in two (16.6%), lower outer quadrant in one (8.4%), and central quadrant with nipple involvement in two (16.6%). Of the 12 patients, 9 (75%) underwent wide local excision, including 2 who also received partial capsulectomy, while 3 (25%) required radical mastectomy with implant removal. Adjuvant radiation therapy was administered to 6 patients (50%)—5/6 (83.3%) in the excision group and 1/6 (16.7%) in the mastectomy group. No significant differences were observed in distant disease–free survival or overall survival between the two groups. Conclusions: Currently, surgical treatment of ipsilateral breast tumor recurrence following conservative mastectomy and prepectoral breast reconstruction is not reported in the literature, and this study represents the first instance where wide local excision is described. The management of ipsilateral recurrence should be discussed in multidisciplinary meetings and could be performed safely in selected cases, sparing the prosthesis and avoiding radical mastectomy. Full article

Objectives: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. Methods: A Phase I/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and ⁹⁹Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. Results: From 2008–2025, 31 ECOG 0–2 patients (10 male) aged 33–75 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 ± 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1–4 days) except for 6–7 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg/m² 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to ⁹⁹Tc differentials within 6.1 ± 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. Conclusions: Suffusion for metastatic malignancies appears safe and warrants further investigation. Full article

Dysregulation contributes to Alzheimer’s disease (AD) pathophysiology. Zinc therapy promotes enterocyte copper sequestration, potentially reducing systemic copper. Individual biological responses may vary. Methods: ZINCAiD was a 24-week, randomized, double-blind, placebo-controlled phase II trial assessing zinc therapy in individuals with mild cognitive impairment (MCI) due to AD (EudraCT No.: 2019-000604-15; registered on 26 March 2020). Participants were randomized 2:1 to receive elemental zinc (135 mg/day for 12 weeks, then 65 mg/day) or placebo. Ceruloplasmin was measured at predefined intervals for safety monitoring, blinded to the investigators. Post hoc, “Zinc Responders” were defined by ≥20% reduction in ceruloplasmin at week 12. The primary cognitive endpoint was the Cognitive Composite 2 scale (CC2); secondary endpoints included MMSE and CDR-Sob. Findings: Of the 48 participants randomized, 9 discontinued, primarily due to unrelated clinical deterioration; 39 had complete ceruloplasmin data. Two serious adverse events occurred in the Placebo group. Mild gastrointestinal symptoms occurred in eight participants, with only four leading to dropout. In the primary zinc vs. placebo analysis, no significant differences emerged in cognitive outcomes. A post hoc exploratory analysis stratified participants by pharmacodynamic response: 12 individuals with MCI due to AD (31%) met the criteria for “Zinc Responder,” defined by ≥20% reduction in serum ceruloplasmin at week 12. Only Zinc Responders maintained cognitive stability over 24 weeks, whereas the combined group of Zinc Non-Responders and placebo-treated participants showed a significant decline. For the composite cognitive score (CC2), the interaction between visit and response group was significant (p = 0.030), with deterioration observed only in the Non-Responder + Placebo group (Δ = –2.72, p < 0.0001 vs. –0.71, p = 0.35 in Responders). Similar patterns were observed for CDR-Sob (interaction p = 0.017) and MMSE (trend p = 0.09). Interpretation: Zinc therapy stabilized cognition in a pharmacodynamically defined MCI subgroup. These exploratory findings suggest serum ceruloplasmin as a feasible biomarker of target engagement. Larger trials are needed for confirmation. Full article

There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic cell transplantation (HCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.5%), probable (26.9%) and possible (59.5%). Among 66 proven and probable IFIs, 53% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.8%) patients had acute myelogenous leukemia, and 40.9% had received HCT. Forty-eight (72.7%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16–44). Fluconazole and posaconazole were the most frequently received antifungal prophylaxis. ISA was prescribed as first-line therapy in 31 (46.9%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.1%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p = 0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HCT patients with and without bIFIs. Full article

Background: Chronic illnesses pose a major global health challenge with an estimated 1.56 billion people affected worldwide in 2025, and 85% of these being older adults facing at least one chronic condition. These patients are particularly vulnerable to severe influenza complications and higher mortality rates due to weakened immune responses; in addition, vaccination rates in China remain significantly lower than those in developed nations. Methods: This review examines how chronic conditions exacerbate influenza-related effects through immune dysfunction and metabolic imbalances, and how influenza infection worsens chronic diseases by triggering inflammation, suppressing immunity, and causing secondary infections that lead to respiratory complications, cardiac complications, and blood sugar disturbances. Results: A bidirectional adverse interaction exists in which chronic illnesses increase influenza severity via poor immunity, while influenza accelerates chronic disease progression (e.g., cardiac events and diabetic ketoacidosis). Vaccination reduces hospitalization by 32–52% in patients with lung disease and mortality by 16–46% in diabetic patients, with good safety. Conclusions: The findings emphasize the urgent need for improved vaccination strategies in patients with chronic diseases. Such strategies are crucial to reducing disease burden, enhancing clinical outcomes, and improving quality of life, while also providing critical evidence for the development of public health policies. Full article

Molecular imaging and precision therapies are transforming ophthalmology, enabling earlier and more accurate diagnosis and targeted treatment of sight-threatening diseases. This review focuses on age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis, examining high-resolution imaging techniques such as optical coherence tomography (OCT), OCT angiography, MALDI-MSI, and spatial transcriptomics. Artificial intelligence supports these methods by improving image interpretation and enabling personalized analysis. The review also discusses therapeutic advances, including gene therapies (e.g., AAV-mediated RPE65 delivery), stem cell-based regenerative approaches, and biologics targeting inflammatory and neovascular processes. Targeted molecular therapies targeting specific signaling pathways, such as MAPK, are also explored. The combination of single-cell transcriptomics, proteomics, and machine learning facilitates the development of personalized treatment strategies. Although these technologies hold enormous potential, their implementation in routine clinical care requires further validation, regulatory approval, and long-term safety assessment. This review highlights the potential and challenges of integrating molecular imaging and advanced therapies in the future of precision ophthalmic medicine. Full article

Early-onset colorectal cancer (EOCRC) is emerging as a significant global health concern, particularly among individuals under the age of 50. This alarming trend has coincided with an increase in the consumption of processed foods that often rely heavily on synthetic preservatives. At the same time, these additives play a critical role in ensuring food safety and shelf life. Growing evidence suggests that they may contribute to adverse gut health outcomes, which is a known risk factor in colorectal cancer development. At the same time, synthetic preservatives serve essential roles such as preventing microbial spoilage, maintaining color, and prolonging shelf life. Natural preservatives, on the other hand, not only provide antimicrobial protection but also exhibit antioxidant and anti-inflammatory properties. These contrasting functions form the basis of current discussions on their safety and health implications. Despite their widespread use, the long-term health implications of synthetic preservatives remain inadequately understood. This review synthesizes recent clinical, epidemiological, mechanistic, and toxicological data to examine the potential link between synthetic food preservatives and EOCRC. Particular focus is placed on compounds that have been associated with DNA damage, gut microbiota disruption, oxidative stress, and chronic inflammation, which are the mechanisms that collectively increase cancer risk. In contrast, natural preservatives derived from plants and microbes are gaining attention for their antioxidant, antimicrobial, and possible anti-inflammatory effects. While these alternatives show promise, scientific validation and regulatory approval remain limited. This review highlights the urgent need for more rigorous, long-term human studies and advocates for enhanced regulatory oversight. It advocates for a multidisciplinary approach to developing safer preservation strategies and highlights the importance of public education in making informed dietary choices. Natural preservatives, though still under investigation, may offer a safer path forward in mitigating EOCRC risk and shaping future food and health policies. Full article

Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and long-term toxicity study and to elucidate the in vivo metabolic pathways of 221s (2,9) in order to provide critical insights into the observed toxicity. In the acute toxicity study, a single oral dose of 221s (2,9) at 3000 mg/kg in mice produced no clinical signs of toxicity or mortality, indicating an MTD of 3000 mg/kg. In a subsequent 12-week repeated-dose toxicity study in rats, doses of 20, 40, and 80 mg/kg were well tolerated, with no adverse clinical observations or deaths. Notably, organ coefficient analysis revealed transient lung injury, which resolved following a 4-week recovery period. The metabolite identification study indicated that metabolism in rats is predominated by Phase II metabolites, potentially contributing to the low toxicity of 221s (2,9). Further investigation into the impact of the drug metabolic enzyme–transporter interplay on the in vivo disposition of 221s (2,9) is warranted. Full article

Background: The objective of this study was to assess the efficacy and safety of faricimab in diabetic macular edema (DME) in patients who were treatment-naïve or previously treated in a real-world setting. Methods: This was a retrospective, observational, single-center study that included 105 eyes from 79 patients diagnosed with DME and treated with intravitreal faricimab between January 2024 and January 2025. Patients were categorized into two groups according to their treatment history, namely treatment-naïve eyes and eyes previously treated (switch group). Functional (best-corrected visual acuity, BCVA) and anatomical (central foveal thickness, CFT; macular volume, MV) outcomes were assessed. The safety of faricimab was evaluated from changes in intraocular pressure and the occurrence of adverse events. Results: BCVA improved significantly in both groups, with a mean gain of +0.16 in treatment-naïve eyes and +0.10 in switch eyes. The mean reduction in CFT was −53.7 µm in the naïve group and −37.8 µm in the switch group. MV decreased by −0.4 mm³ overall, with significant reductions in both groups. No adverse events were reported, confirming the safety of faricimab in routine clinical practice. Conclusions: Faricimab showed significant improvements in functional and anatomical outcomes in patients with DME, regardless of the use of previous anti-VEGF therapies. These findings support the effectiveness and safety of faricimab in a real-world clinical setting and reinforce its potential as a valuable treatment option for DME. Full article

Background: This study aimed to evaluate the risk of upper gastrointestinal (UGI) adverse events (AEs) associated with oral anticoagulants (OACs) and identify potential interactions with cardiovascular (CV) drugs. Methods: Individual case safety reports (ICSRs) from the FDA Adverse Event Reporting System from July 2014 to December 2023 were analyzed. Dataset I was constructed to assess the associations between OACs and UGI AEs using disproportionality analysis. Dataset Ⅱ included OAC-related ICSRs to explore potential interactions with CV drugs through logistic regression. Positive signals were defined as potential associations identified by disproportionality analysis metrics, such as reporting odds ratios (RORs) or adjusted RORs (aRORs) accounting for confounders. Results: Dataset I included 12,905,290 ICSRs, and a positive signal for dabigatran was detected with an ROR of 1.19 (95% CI, 1.13–1.25). A total of 364,044 OAC-related ICSRs were included in dataset II. At the pharmacologic drug class level, several positive signals were identified, represented as aRORs with 95% CIs: for warfarin, amiodarone analogs (1.22; 1.04–1.43); for apixaban, angiotensin-converting enzyme inhibitors (1.34; 1.24–1.45), angiotensin receptor blockers (1.23; 1.14–1.33), dihydropyridine calcium channel blockers (1.30; 1.21–1.41), and digitalis glycosides (1.72; 1.49–2.00); and for edoxaban, angiotensin receptor blockers (1.88; 1.48–2.37), amiodarone analogs (1.73; 1.06–2.85), and anti-platelets (1.56; 1.20–2.03). No signals were observed for rivaroxaban or dabigatran. At the individual drug level, 62 OAC-CV pairs were identified as having potential interactions. Conclusions: Drug-specific interaction profiles should be considered to ensure safe and personalized use of OACs in clinical practice. Full article

Background/Objectives: This systematic review evaluated the efficacy and safety of Emotional Freedom Techniques (EFT) for anxiety disorders, compared with conventional and alternative therapies. Methods: A comprehensive literature search was conducted across nine electronic databases up to February 2025, including only parallel-group randomized controlled trials (RCTs) that investigated EFT as a standalone intervention for anxiety symptoms. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias 2.0 tool. Results: Seven RCTs with 506 participants were included. Populations ranged from clinical to non-clinical groups. EFT interventions varied in duration (1–56 sessions), with control groups including no treatment, supportive interviews, cognitive behavioral therapy (CBT), breathing therapy, and progressive muscle relaxation. All six studies comparing EFT to no intervention reported significant reductions in anxiety symptoms in favor of EFT. Compared to active controls, EFT showed similar or superior effects to breathing therapy and muscle relaxation but no significant difference from CBT. Most studies showed “some concerns” in risk of bias, mainly due to self-reported outcomes and lack of blinding. Conclusions: EFT appears to be a promising and safe complementary intervention for reducing anxiety symptoms, with additional benefits for related psychological outcomes. However, methodological limitations and heterogeneity among studies preclude firm conclusions. High-quality RCTs using standardized protocols and objective outcome measures are warranted to confirm these findings and to explore the effectiveness of EFT as an adjunct to conventional therapies. Full article

Background: In Italy, workplace safety regulations require the training of first-aid officers to manage medical emergencies, including acute coronary syndromes. Although clinical guidelines recommend the early use of acetylsalicylic acid in myocardial infarction, little is known about the implementation of this recommendation in practice. This study aims to assess the use of acetylsalicylic acid for ST-elevation myocardial infarction (STEMI) in workplace and non-workplace settings, with a focus on informing the evaluation and improvement of first-aid training programs and emergency response protocols. Methods: We conducted a retrospective, observational cohort study using 2019 data from the Regional Agency for Emergency Urgency. Cases were identified and stratified by event location (workplace vs non-workplace), to analyze patterns of acetylsalicylic acid administration. A logic model has been developed to program a stepwise plan of action for policies development. Results: A total of 2174 STEMI cases were identified, of which 380 (17.5%) occurred in the workplace. Workplace cases were younger and more likely to be male. Acetylsalicylic acid was administered in only 31 cases overall, with no statistically significant difference between settings. This assessment advocates for the implementation of targeted actions, which may include updates to current legislation and policies. Conclusions: These findings highlight an urgent need to systematically evaluate existing workplace first-aid training and emergency protocols. Integrating modules on acetylsalicylic acid administration into training curricula, along with performance monitoring mechanisms, may significantly enhance early STEMI management and patient outcomes. Updating safety programs to align with evidence-based practices should follow a structured approach. Full article

Large language models (LLMs) have the potential to transform healthcare by assisting in documentation, diagnosis, patient communication, and medical education. However, their integration into clinical practice remains a challenge. This perspective explores the barriers to implementation by synthesizing recent evidence across five challenge domains: workflow misalignment and diagnostic safety, bias and equity, regulatory and legal governance, technical vulnerabilities such as hallucinations or data poisoning, and the preservation of patient trust and human connection. While the perspective focuses on barriers, LLM capabilities and mitigation strategies are advancing rapidly, raising the likelihood of near-term clinical impact. Drawing on recent empirical studies, we propose a framework for understanding the key technical, ethical, and practical challenges associated with deploying LLMs in clinical environments and provide directions for future research, governance, and responsible deployment. Full article

Fractional laser (FL) and fractional radiofrequency (FRF) are effective treatments for atrophic acne scars, yet comparative data in Asian populations with darker skin types remain limited. This retrospective cohort study compared the clinical effectiveness and safety of FL and FRF in Thai patients aged 18–60 years with Fitzpatrick skin types III–IV who underwent at least two treatment sessions between 2012 and 2023. Baseline characteristics were balanced using propensity score stratification, and missing data were addressed through multiple imputation with chained equations. The primary endpoint was the proportion of patients achieving ≥25% improvement in scarring at 6 months, with equivalence testing performed using a 20% margin. A total of 397 patients (254 FL, 143 FRF) were included, with balanced baseline characteristics after stratification. At 6 months, 88.1% of FRF-treated and 71.9% of FL-treated patients achieved the primary endpoint. FRF showed numerically greater mean improvement at all time points, though differences were not statistically significant. FL met the non-inferiority criterion but not equivalence. FRF was associated with significantly higher pain scores (p < 0.001), while adverse events, including post-inflammatory hyperpigmentation, were rare and similar between groups. Both modalities demonstrated meaningful clinical benefit and acceptable safety, although statistical equivalence could not be established and FRF was associated with greater procedural discomfort. Full article