Search Results (6,097)

Background: Hemorrhoidal disease (HD) is a common anorectal condition characterized by symptoms such as bleeding, pain, discomfort and itching. While often underdiagnosed due to patient reluctance to seek care, HD significantly impacts quality of life (QoL). Conservative treatments are preferred for low-grade HD, with increasing interest in natural substance-based therapies. Materials and Methods: A large-scale survey was conducted using a digital platform to collect real-world data (RWD) from patients, pharmacists and physicians. The research assessed perceived effectiveness, safety, tolerability, quality of life (QoL) and usage patterns of NeoFitoroid BioOintment. Quantitative analysis was also performed using a global score (GS) based on Likert scale ratings and their distribution. Results: A total of 2618 participants were included. A strong concordance across the three participating cohorts in the answers provided for all items of the questionnaire was observed. The descriptive analysis revealed high grades of effectiveness, safety and tolerability. Indeed, over 90% of respondents rated the product as “good” or “excellent” in terms of effectiveness and safety. Conclusions: These findings underscore the treatment’s effectiveness, safety, tolerability and positive influence on QoL in HD patients. Full article

Background/Objectives: Standard dental practice is being reshaped by digital technologies, and artificial intelligence (AI) is emerging as one of the most challenging recent innovations. Methods: The present study assessed the interest of Romanian dentists in the integration of AI into their current practice through an anonymous questionnaire distributed to 200 respondents. The questionnaire addressed the integration of AI in dentistry by analyzing the following areas of intervention: stages of patient care, perceived impact on the doctor–patient relationship, data security, implementation costs, and the legislative framework. Results: The results showed that 53.6% of dentists reported low difficulties, 37.3% reported moderate difficulties, and 9.1% reported high difficulties with using digital tools. Dentists’ reported willingness to adopt AI-based solutions was as follows: 58.6% were very willing, 30% were moderately willing, and only 11.4% were not very willing. Currently, 80.5% already use digital techniques in their daily practice. The participants emphasized the need to maintain a strong doctor–patient relationship while recognizing the benefits of increased efficiency. They were aware of the risk of diminishing human connection and trust. Also, data security and the financial stress associated with implementing and maintaining new systems were seen as major obstacles. Conclusions: The dentists surveyed showed an increased interest in modern digital technologies, provided that there is a clear legal framework, a strong data protection system, and the preservation of the doctor–patient relationship based on trust and confidentiality that defines the medical profession. Full article

Background/Objectives: Nutrigenetics has emerged as a promising tool to advance personalized nutrition strategies. This study aimed to analyze the scope and perception of Mexican dietitians regarding nutritional genomics with an emphasis on nutrigenetics’ use in clinical practice. Methods: A survey was conducted online among dietitians in Mexico to assess their educational background, awareness of nutrigenetic testing, use in practice, and interest in further training through 33 questions. Results: One hundred and thirty participants from states across six Mexican regions completed the survey, and most of respondents had a bachelor’s degree. The analysis showed that while most respondents were familiar with the concepts of nutrigenomics and nutrigenetics, 92.3% did not incorporate genetic testing into their practice; the main barriers of their use were misinformation, limited access to reliable resources, and ethical concerns surrounding genetic testing. Although 86.2% expressed interest in learning about nutrigenetics, only 31.5% were willing to invest in further training. Social media and non-academic sources were important sources of information, raising concerns about their inaccurate content and highlighting their importance in completing the curricula. Patients’ demand for genetic testing is limited and directed by disease prevention interests. Conclusions: Nutrigenetics is currently an area with limited practical application among Mexican dietitians; however, it is perceived as a valuable tool for future daily practice. The gap between perception and application underscores the need to integrate nutrigenetics into undergraduate curricula and to provide accessible, evidence-based professional development; these are essential to promote the ethical and effective use of nutrigenetics and support the transition toward personalized nutrition. Full article

Background: Breast cancer, particularly the luminal subtype, often responds to endocrine therapies. However, 20–30% of patients develop resistance, resulting in more aggressive disease. Long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. Objective: This study aimed to evaluate the role of the lncRNA insulin-like growth factor 2 antisense (IGF2-AS) in tamoxifen-resistant breast cancer and assess its potential as a therapeutic target. Methods: Two tamoxifen-resistant breast cancer cell lines (TAMR-V and TAMR-H) were used to assess IGF2-AS expression via qPCR. Knockdown experiments with siRNA evaluated the role of IGF2-AS in cell proliferation, invasion, and migration. Next-generation sequencing (NGS) analyzed gene expression differences between the cell lines. Kaplan–Meier survival analysis determined the clinical significance of IGF2-AS expression in breast cancer patients. Results: IGF2-AS expression was significantly upregulated in TAMR-V and TAMR-H cell lines compared to control MCF-7 cells. Knockdown of IGF2-AS reduced cell proliferation and invasion in TAMR-V cells but did not significantly affect TAMR-H cells, indicating a cell line-specific role in tamoxifen resistance. NGS revealed differential gene expression profiles between TAMR-V and TAMR-H cells, suggesting variability in resistance mechanisms. Survival analysis demonstrated that higher IGF2-AS expression was associated with poorer prognosis in breast cancer patients, including those with hormone-positive and triple-negative subtypes. Conclusions: IGF2-AS is upregulated in tamoxifen-resistant breast cancer and promotes cell proliferation and invasion in a cell line-specific manner. Its differential expression in TAMR-V and TAMR-H cells highlights the complexity of resistance mechanisms, suggesting IGF2-AS as a potential therapeutic target for overcoming tamoxifen resistance. Full article

Background/Objectives: Ethical challenges in healthcare require awareness and adherence to professional codes of ethics, particularly in interdisciplinary settings such as tertiary hospitals. This study aimed to assess the attitudes and awareness of healthcare professionals regarding codes of ethics at the University Hospital of Split in Croatia, which did not have an institutional code at the time of the study. Methods: A cross-sectional survey using a structured, anonymous questionnaire was distributed both physically across hospital departments and online via email. Welch’s t-test, ANOVA, Kruskal–Wallis, and correlation tests were used to assess associations between favourability scores and participant characteristics. Linear and logistic regression analyses further examined predictors of favourable attitudes. Results: Of 442 returned questionnaires, 377 were complete and included in the analysis, mainly from nurses (56.5%) and physicians (42.7%). The median favourability score was 83.8% (88/105; IQR 78.1–88.6), with 87.0% scoring above the favourable threshold (≥75%). Female gender and higher education were significantly associated with more favourable attitudes. Participants strongly endorsed core principles such as patient confidentiality and autonomy, yet 57.6% considered ethics education during training inadequate, and only 36.3% viewed dual practices as a conflict of interest. Most respondents reported adherence to ethical standards (85.4%), while only over half were familiar with their professional ethics code (64.5%) and the hospital Ethics Committee (56.2%); a total of 66.3% supported introducing a hospital-specific code. Awareness and support for ethical structures were higher among women and those with more education. Conclusions: This study reveals a gap between personal ethical commitment and institutional ethical infrastructure. Strengthening ethics education and implementing a hospital-specific ethics code may enhance organisational ethical culture. Full article

A multicenter molecular biomarker survey was conducted in Multiple Sclerosis (MS) centers across Central-Eastern European countries, encompassing a population of 107 million. Our aim was to provide a “snapshot” for future studies investigating the use of molecular biomarkers in MS. A self-report questionnaire was distributed via email to MS centers in seven Central-Eastern European countries (Croatia, Czech Republic, Poland, Romania, Serbia, Slovakia, and Slovenia) and to four reference centers (two in Austria, one in Germany, and one in Denmark), focusing on cerebrospinal fluid (CSF) analysis and molecular biomarkers in MS. Responding centers routinely request CSF oligoclonal band (OCB) testing in suspected MS cases, although no consensus exists on the number of CSF-restricted bands required to define OCB positivity, either within or between countries. More than half of the surveyed centers in the Czech Republic, Slovakia, Slovenia, and the reference centers request kappa free light chain (κFLC) testing in patients with suspected MS. Neurofilament light chain (NfL) is frequently used as a molecular biomarker for MS in Romania, Slovakia, and the reference centers. In summary, besides the use of CSF-specific OCB there is no consensus among the surveyed countries regarding the use of molecular biomarkers in MS. Full article

Background/Objectives: In the last decade, several studies revealed individual response variability to different antiplatelet agents, and patients who have no response to these drugs are considered poor responders. Some studies explored platelet function during antiplatelet treatment to identify those patients with “high on-treatment platelet reactivity” (HPR), which exposes them to increased risk of major adverse cardiovascular events (MACE). Methods: We conducted a study with patients with ST-elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, including long-term follow-up after 5 years. We used thromboelastography, the total thrombus formation analysis system, and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) to analyze HPR with different methods; selected laboratory parameters were measured during hospitalization to check significant correlations. Results: We identified STEMI patients treated with DAPT with HPR as a risk group for MACE in a 5-year follow-up. Additionally, we have shown that HPR is associated with atherosclerosis by analyzing lipid profile parameters. Conclusions: High on-treatment platelet reactivity (HPR) increases the risk of major adverse cardiovascular events in the long term, especially with elevated C-reactive protein or an atherogenic lipid profile. Standardizing HPR assessment is crucial for optimizing individualized antiplatelet therapy and improving patient outcomes post-STEMI. Full article

Background: Long COVID can persist for years, but little is known about its prevalence in relation to the number of infections. This study examines the prevalence of long COVID in association with the number of infections and vaccination status. Methods: We analyzed anonymized data on long COVID cases, thrombotic events and polypharmacy from March 2020, provided by the Data Analysis Control Department for the population assigned to the CST (192,651 at March 2025). Additionally, we analyzed responses to a long COVID symptom-specific survey distributed in March 2024 to individuals aged 18 to 75 years from the CST population diagnosed with COVID-19 as of December 2023 (n = 43,398; 3227 respondents). Symptomatic patients suspected of having long COVID underwent blood tests to exclude alternative diagnoses. Results: The overall detected prevalence of long COVID was 2.4‰, with higher frequency among women aged 30–59 years (p < 0.001). The survey, combined with specific blood tests, improved detection rates by 26.3%. Long COVID prevalence was 3–10 times higher in individuals with three or more infections than in those with only one recorded infection (based on survey/CST data, respectively). The absolute number of thrombotic events among individuals aged >60 doubled from 2020 to 2024, occurring in both vaccinated and unvaccinated individuals, as well as in those with or without prior documented COVID-19 infection, including in patients without chronic treatments. Conclusions: We found a link between SARS-CoV-2 reinfection and long COVID, and a post-pandemic rise in thrombotic events across all populations, regardless of vaccination or prior infection. Findings support continued COVID-19 diagnosis in suspected cases and mask use by healthcare workers treating respiratory patients. Full article

Background/Objectives: Multifocal Motor Neuropathy (MMN) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) are immune-mediated polyneuropathies often treated with immunoglobulin therapy. They were prioritized for COVID-19 vaccination during the pandemic. However, their immune response following COVID-19 vaccination remains unclear. We investigated short- and long-term immune responses to COVID-19 vaccination in patients with MMN and CIDP compared to controls. Methods: In a prospective observational study, patients with CIDP or MMN and matched controls were followed over 24 months. Controls were age- and sex-matched 1:9. Participants received COVID-19 vaccines in accordance with the Danish vaccination program. Primary outcomes were levels of SARS-CoV-2 IgG antibodies and virus-neutralizing capacity. A positive vaccine response was defined as IgG > 225 AU/mL and neutralizing capacity ≥ 25%. Results: We included 34 patients and 306 matched controls. While baseline SARS-CoV-2 IgG levels were similar, controls exhibited higher IgG levels at 6- (mean difference, 88%; p = 0.008), 18- (91%; p = 0.023), and 24 months (160%; p < 0.001). Neutralization capacity was also higher in controls at 6 (10%, p = 0.004), 18 (7%, p < 0.001), and 24 months (9%, p = 0.002). Despite this, the proportion of vaccine responders did not differ between the two groups after 24 months (p = 0.196). In patients receiving immunoglobulin therapy, IgG levels were lower than in controls at 24-month follow-up alone (56%, p < 0.001); all demonstrated a positive vaccine response. Conclusions: Patients with CIDP and MMN demonstrated a positive humoral response to COVID-19 vaccination. Although IgG and neutralization levels were lower than in controls, all patients receiving immunoglobulin therapy were vaccine responders. Full article

MRGPRX2 (Mas-related G protein-coupled receptor member X2) is implicated in mast cell (MC)-driven disorders due to its ability to bind diverse ligands, which may be G-protein-biased or balanced, with the latter activating both G-proteins and the β-arrestin pathway. Icatibant, a peptide drug, produces injection-site reactions in most patients and is used experimentally to probe MRGPRX2 function in skin tests. While reported to be G-protein-biased, it is unknown how skin MCs respond to icatibant, although these are the primary target cells during therapy. We therefore compared responses to icatibant with those induced by the balanced agonist substance P (SP) in skin MCs. Degranulation and desensitization were assessed via β-hexosaminidase release, receptor internalization by flow cytometry, and downstream signaling by immunoblotting. Skin MCs degranulated in response to SP and icatibant, relying on Gi proteins and calcium channels; Gq and PI3K (Phosphoinositide 3-kinase) contributed more strongly to exocytosis following icatibant, while JNK (c-Jun n-terminal kinase) was more relevant for SP. Both agonists activated ERK, PI3K/AKT, and (weakly) p38. Surprisingly, and in contrast to the LAD2 (Laboratory of Allergic Diseases 2 mast cell line) MC line, icatibant was at least as potent as SP in eliciting MRGPRX2 internalization and (cross-)desensitization in skin MCs. These findings suggest that icatibant functions differently in primary versus transformed MCs, acting as a fully balanced ligand in the former by triggering not only degranulation but also receptor internalization and desensitization. Therefore, not only the ligand but also the MRGPRX2-expressing cell plays a decisive role in whether a ligand is balanced or biased. These findings are relevant to our understanding of icatibant’s clinical effects on edema and itch. Full article

Background/Objectives: Leishmania spp. are protozoan parasites transmitted by female sandflies (Phlebotomus or Lutzomyia). Clinical manifestations depend on species and host immunity. While cutaneous and visceral forms prevail, mucocutaneous involvement—particularly isolated nasal septum leishmaniasis—is rare and frequently misdiagnosed as an inflammatory, infectious, or neoplastic condition. Risk factors associated with mucocutaneous leishmaniasis include systemic or local immunodeficiency, prior renal transplantation, treatment with chronic inhaled steroids, residence in endemic areas or travel to such regions, and previous Leishmania infections. Immunosuppressed patients are at higher risk for atypical presentations and delayed diagnosis, which can result in extensive tissue destruction. Early clinical suspicion, histopathological confirmation, and prompt therapy are essential to prevent permanent mucosal damage. Therefore, a multidisciplinary approach is needed for adequate evaluation and effective treatment. Methods: A 67-year-old man with rheumatoid arthritis on methotrexate reported a two-year history of right-sided nasal obstruction and ulceration that failed to respond to antibiotics. He did not present systemic symptoms. Results: Facial CT revealed a septal deviation; the patient underwent septoplasty, and biopsy confirmed Leishmania amastigotes. Serology (rK39 immunochromatographic test) was positive. He was treated with liposomal amphotericin B at 4 mg/kg/day for five days, followed by miltefosine at 100 mg/day orally for 14 days. At an eight-week follow-up, the nasal mucosa was fully healed, obstruction was resolved, and there was no evidence of recurrence. Conclusions: Although nasal septum leishmaniasis is uncommon, it should be considered in the differential diagnosis of chronic nasal lesions, especially in immunocompromised patients or those from endemic regions. Definitive diagnosis requires biopsy with histological or molecular confirmation. Combined liposomal amphotericin B and miltefosine therapy yields high cure rates and prevents mucosal destruction. Early recognition is critical to avoid diagnostic delays and long-term sequelae. Full article

Uterine fibroids are one of the leading health concerns for women worldwide, affecting up to 80% of women by the age of 50. While recent advancements have improved the diagnosis and treatment of fibroids, the current standard of care still faces important limitations due to the need for a personalized approach to treatment. Uterine fibroid embolization (UFE) has emerged as a promising minimally invasive alternative to traditional surgery, offering advantages such as shorter recovery times, fewer complications, and the preservation of the uterus. However, despite their highly reported effectiveness, only about 1% of eligible patients are offered UFE. This drastic underutilization is partially due to limited physician confidence in predicting patient-specific outcomes. To address this challenge, in this study, we aim to present an objective analysis of the factors influencing UFE success and introduce a scalable and interpretable machine learning (ML) system designed to support clinical decision-making. We have curated a dataset that includes 74 patients, with a total of 311 fibroids for our analysis. We have also developed two sets of ML models for predicting UFE procedure success based on a pre-operative MRI scan as the input. The first model predicts overall procedure success and the likelihood of relieving specific symptoms, achieving an accuracy of 75% (AUC = 0.74) for procedure outcome and 81–88% (AUC = 0.81–0.87) for different symptoms, respectively. The second set of models predicts the success of each individual fibroid responding to the treatment, achieving a 76% accuracy and 75% F-1 score. The AI models in this study can potentially provide patient-specific prediction of procedure effectiveness on both patient-level and fibroid-level, enhancing procedure referral accuracy. Full article

Background: Neoadjuvant chemotherapy (NAC) is the important and effective approach to treat locally advanced breast cancer (LABC). The prediction of response to NAC prior to start is an efficient approach to obtaining perspective about the effectiveness of treatment. The objective of this study is to design a machine learning pipeline to predict tumor response to NAC treatment for patients with LABC using the combination of clinical features and radiomics computed tomography (CT) features. Method: A total of 858 clinical and radiomics CT features were determined for 117 patients with LABC to predict the tumor response to NAC treatment. Since the number of features is greater than the number of samples, dimensionality reduction is an indispensable step. To this end, we proposed a novel hybrid feature selection to not only select top features but also optimize the classifier hyperparameters. This hybrid feature selection has two phases. In the first phase, we applied a filter-based strategy feature selection technique using matrix rank theorem to remove all dependent and redundant features. In the second phase, we applied a genetic algorithm which coupled with the SVM classifier. The genetic algorithm determined the optimum number of features and top features. Performance of the proposed technique was assessed by balanced accuracy, accuracy, area under curve (AUC), and F1-score. This is the binary classification task to predict response to NAC. We consider three models for this study including clinical features, radiomics CT features, and a combination of clinical and radiomics CT features. Results: A total of 117 patients with LABC with a mean age of 52 ± 11 were studied in this study. Of these, 82 patients with LABC were the responder group (response to NAC) and 35 were the non-response group to chemotherapy. The best performance was obtained by the combination of clinical and CT radiomics features with Accuracy = 0.88. Conclusion: The results indicate that the combination of clinical features and CT radiomic features is an effective approach to predict response to NAC treatment for patients with LABC. Full article

The challenge for healthcare policy makers, managers and practitioners is finding ways to effectively collaborate with patients and community to plan, deliver and evaluate services. The study examined how managers engage the community with the strategic redesign of health services. The study focused on four large scale redevelopment projects, valued at A$2.8B, occurring within a health district in New South Wales, Australia. The study employed a multiple qualitative methods design comprising semi-structured interviews and focus groups. Participants were professionals (n = 24) involved in the strategic planning of health facility redevelopment. Thematic analysis was used to identify, analyse and report findings. Three issues emerged as significant factors influencing engagement, including the following: establishing a new mindset to service planning and delivery; future proofing service delivery; and management of stakeholder expectations. The unique contribution of the research is the identification of three interwoven strategies with 30 actions proposed to assess, understand and respond to external factors: 1. Foster an environment that allows for flexible and adaptable thinking and discussion; 2. Develop systems, structures and processes that facilitate engagement; 3. Encourage systems thinking for effective continuous service provision and redevelopment. Large scale redevelopment projects provide a platform for the strategic redesign of health services. When doing so, engaging the community with strategic planning, implementation and evaluation of healthcare services can lead to improved care outcomes. Full article

Introduction: Osteoarthritis (OA) is a chronic degenerative joint disease with limited treatment options focused primarily on symptom management. Emerging evidence suggests that dietary interventions may influence inflammation and pain through modulation of the gut microbiome and metabolome. Methods: We conducted a 4-week open-label pilot trial evaluating the effects of an anti-inflammatory dietary intervention (ITIS diet) in 20 patients with knee OA (ClinicalTrials.gov ID: NCT05559463, registered prior to enrollment; sponsor: University of California, San Diego; responsible party: Monica Guma; study start date: 1 October 2021). The following were assessed before and after the intervention: (1) clinical outcomes; (2) gut and salivary microbiomes; and (3) salivary, stool, and plasma metabolomes. Responders were defined as patients achieving ≥30% reduction in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores. Results: The ITIS diet was well-tolerated, with good adherence (66.2%) and a significant improvement in clinical outcomes, including reduced pain and improved overall health measured with the visual analog scale (VAS). Responders (n = 8) showed distinct gut microbiome and metabolome profiles compared to non-responders (n = 12). Notably, taxa within the Lachnospiraceae family exhibited dynamic, bidirectional shifts post-intervention: Anaerostipes and Limivivens were enriched among responders and negatively correlated with pain scores, while Oliverpabstia and Fusicatenibacter were depleted following dietary intervention. These taxa also showed strong correlations with anti-inflammatory metabolites, including hydroxydecanoic acid derivatives and pyridoxine. Furthermore, subsequent network analysis revealed more structured and selective microbiome–metabolome interactions in responders, specifically post-intervention. Conclusions: This pilot study shows that a short-term anti-inflammatory dietary intervention was associated with meaningful changes in the gut microbiome and metabolome. Members of the Lachnospiraceae family emerged as key taxa associated with pain reduction and anti-inflammatory metabolite production. Our findings suggest that specific microbial responses—rather than global diversity changes—may underlie dietary responsiveness in OA. Although exploratory and limited by sample size, our results support further investigation into personalized, microbiome-informed nutritional strategies for OA management. Full article