Search Results (711)

Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article

The invention of antibacterial agents (antibiotics) was a significant event in the history of the human race, and this invention changed the way in which infectious diseases were cured; as a result, many lives have been saved. Recently, antibiotic resistance has developed as a result of excessive use of antibiotics, and it has become a major threat to world health. ARGs are spread across biomes and taxa of bacteria via lateral or horizontal gene transfer (HGT), especially via conjugation, transformation, and transduction. This review concerns transduction, whereby bacteriophages or phages facilitate gene transfer in bacteria. Bacteriophages are just as common and many times more numerous than their bacterial prey, and these phages are much more influential in controlling the population of bacteria. It is estimated that 25% of overall genes of Escherichia coli have been copied by other species of bacteria due to the HGT process. Transduction may take place via a generalized or specialized mechanism, with phages being ubiquitous in nature. Phage and virus-like particle (VLP) metagenomics have uncovered the emergence of ARGs and mobile genetic elements (MGEs) of bacterial origins. These genes, when transferred to bacteria through transduction, confer resistance to antibiotics. ARGs are spread through phage-based transduction between the environment and bacteria related to people or animals, and it is vital that we further understand and tackle this mechanism in order to combat antimicrobial resistance. Full article

Desmoid tumors are rare, deep-seated myofibroblastic tumors with an unpredictable course, ranging from spontaneous regression to infiltrative growth and locally aggressive behavior, but without metastatic potential. Over the past few decades, advances in understanding their natural history, underlying molecular pathways, and patient care priorities have shifted the treatment paradigm from upfront surgical resection to initial active surveillance, with further treatment dictated by continuous disease progression or associated symptoms. However, there are still specific scenarios where surgery continues to play an important role in locoregional treatment and symptom control. This article will focus on current treatment strategies and surgical indications in adult patients with desmoid tumors, emphasizing patient selection, anatomic site-specific considerations, and surgical technique. Understanding the nuanced role of surgery within the growing treatment landscape is key for individualized patient care in a multidisciplinary setting to optimize quality of life and long-term outcomes. Full article

Background: A growing body of evidence suggests that diet can modify Parkinson’s disease (PD) outcomes, although there is disagreement about what should be included and excluded in such a diet. Existing evidence suggests that adherence to the MIND and Mediterranean (MEDI) diets are associated with reduced PD symptoms, but only a few variables from the adherence scales are responsible for the statistically observed improvement. Objectives: The goal was to use patient-reported outcomes in a large cohort to identify the foods and dietary patterns (PRO diet) most strongly associated with the fewest PD symptoms over time, and to develop a composite adherence scale to enable comparisons between MEDI, MIND, and PRO. Methods: Data were obtained from the prospective longitudinal natural history study and from Modifiable Variables in Parkinsonism (MVP)—a study designed to identify behaviors associated with patient-reported outcomes (PRO-PD). Upon the completion of the binary and food frequency data collection, using various predictive models and considering congruence with historical data, the PRO diet was created via an iterative process. Our goal was to create a new scale and compare its performance to the existing MIND and MEDI scores. The comparison was made at baseline, using the regression models for PRO-PD and the different scales as the predictors. The models were compared via the Akaike Information Criterion (AIC). To examine whether baseline adherence levels predicted subsequent symptom trajectories, the baseline PRO diet adherence and subsequent slope of progression were evaluated. Results: Data from 2290 individuals with PD were available for this analysis. The Mediterranean and MIND diets showed almost identical effects. For both the diets, the effect they had on non-motor symptoms was about twice the effect on motor symptoms. The slopes for the total PRO-PD for MEDI, MIND, and PRO-21 were −64.20467, −64.04220, and −28.61995, respectively. The AIC value differences were substantial (>2), indicating meaningful improvements in the model fit for total PRO-PD, as follows: MEDI: 28,897.24, MIND: 28,793.08, and PRO-21: 27,500.71. The subset of individuals who were most adherent to the PRO-21 diet at baseline had the slowest subsequent progression, as measured by a 43% reduced PRO-PD slope, compared to the less adherent groups. Conclusions: The PRO-21 outperformed the MIND and MEDI diets in the model fit, overcoming the ceiling effects and showing orders of magnitude and superior explanatory power for variance in PD outcomes, despite the smaller per-unit effect sizes. However, its rigorous demands may introduce barriers related to cost, feasibility, and sustainability, underscoring the need for future intervention trials to assess real-world feasibility, adherence, side effects, and clinical impact. Full article

Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and higher production costs in the global pig industry. Our goal was to conduct a comprehensive study correlating both the anti-PRRSV immune response and 21 secondary infectious agents with PRDC severity. Methods: To this end, PRRSV-negative weaners were vaccinated with a PRRSV-2 MLV and put into a farm with a history of PRDC. Subsequently, anti-PRRSV cellular and antibody responses were monitored pre-vaccination, at 28 days post vaccination (dpv) and during PRDC outbreak (49 dpv). NanoString was used to quantify 21 pathogens within the bronchoalveolar lavage (BAL) at the time of necropsy (51 dpv). PRRSV-2 was present in 53 out of 55 pigs, and the other five pathogens (PCMV, PPIV, B. bronchiseptica, G. parasuis, and M. hyorhinis) were detected in BAL samples. Results: Although the uncontrolled settings of field trials complicated data interpretation, multivariate correlation analyses highlighted valuable lessons: (i) high weaning weight predicted animal resilience to disease and high weight gains correlated with the control of the PRRSV-2 field strain; (ii) most pigs cleared MLV strain within 7 weeks, and the field PRRSV-2 strain was the most prevalent lung pathogen during PRDC; (iii) all pigs developed a systemic PRRSV IgG antibody response which correlated with IgG and IgA levels in BAL; (iv) the induction of anti-field strain-neutralizing antibodies by MLV PRRSV-2 vaccination was both late and limited; (v) cellular immune responses were variable but included strong systemic IFN-γ production against the PRRSV-2 field strain; (vi) the most detected lung pathogens correlated with PRRSV-2 viremia or lung loads; (vii) within the six detected pathogens, two viruses, PRRSV-2 and PCMV, significantly correlated with the severity of the clinical outcome. Conclusions: While a simple and conclusive answer to the multifaceted nature of PRDC remains elusive, the key lessons derived from this unique study provide a valuable framework for future research on porcine respiratory diseases. Full article

Emerging evidence suggests a significant association between monocytes and the pathophysiology and prognosis of idiopathic pulmonary fibrosis (IPF). This review aims to systematically evaluate current knowledge regarding blood monocyte counts and their relationship with the etiology, progression, and prognosis of IPF. We conducted a systematic search in the PubMed database for articles published through 17 February 2025, using the MeSH terms “lung diseases, interstitial” and “monocytes,” which yielded 314 results. After filtering for full-text articles in English (n = 242), we included only studies focusing on blood monocyte counts with clinical implications in IPF. Articles relating to other cell types or non-IPF lung diseases were excluded. Our systematic search identified 12 relevant articles. Monocytes play an essential role in regulating inflammatory responses and resolution across multiple diseases, with established but incompletely understood contributions to lung fibrosis development in IPF. Correlations have been demonstrated between elevated blood monocyte counts and the following: (1) the presence and progression of interstitial lung abnormalities, (2) the progression from an indeterminate usual interstitial pneumonia (UIP) pattern on CT scans to definitive IPF, and (3) worse lung function parameters, an increased risk of acute exacerbations, and reduced overall survival in IPF patients. Monocytes serve as critical orchestrators throughout IPF’s natural history—from early interstitial changes to disease progression and acute exacerbations. Targeting monocyte recruitment pathways and reprogramming their differentiation represents a promising therapeutic approach, while circulating monocyte counts offer potential as accessible biomarkers for disease progression and treatment response. Future research should characterize stage-specific monocyte phenotypes to enable precision-targeted interventions. Full article

The natural history of focal non-infected lesions of the abdominal aorta (fl-AA) remains unclear and largely depends on their aetiology. These lesions often involve a focal “tear” or partial disruption of the arterial wall. Penetrating aortic ulcers (PAUs) and intramural hematomas (IMHs) are examples of focal tears in the aortic wall that can either progress to dilatation (saccular aneurysm) or fail to fully propagate through the medial layers, potentially leading to aortic dissection. These conditions typically exhibit a morphology consistent with eccentric saccular aneurysms. The management of focal non-infected pathologies of the abdominal aorta remains a subject of debate. Unlike fusiform abdominal aortic aneurysms, the inconsistent definitions and limited information regarding the natural history of saccular aneurysms (sa-AAAs) have prevented the establishment of universally accepted practice guidelines for their management. As emphasized in the latest 2024 ESVS guidelines, the focal nature of these diseases makes them ideal candidates for endovascular repair (class of evidence IIa—level C). Moreover, the Society for Vascular Surgery just referred to aneurysm diameter as an indication for treatment suggesting using a smaller diameter compared to fusiform aneurysms. Consequently, the management of saccular aneurysms is likely heterogeneous amongst different centres and different operators. Endovascular repair using tube stent grafts offers benefits like reduced recovery times but carries risks of migration and endoleak due to graft rigidity. These complications can influence long-term success. In this context, the use of endovascular bifurcated grafts may provide a more effective solution for treating these focal aortic pathologies. It is essential to achieve optimal sealing regions through anatomical studies of aortic morphology. Additionally, understanding the anatomical characteristics of focal lesions in challenging necks or para-visceral locations is indeed crucial in device choice. Off-the-shelf devices are favoured for their time and cost efficiency, but new endovascular technologies like fenestrated endovascular aneurysm repair (FEVAR) and custom-made devices enhance treatment success and patient safety. These innovations provide stent grafts in various lengths and diameters, accommodating different aortic anatomies and reducing the risk of type III endoleaks. Although complicated PAUs and focal saccular aneurysms rarely arise in the para-visceral aorta, the consequences of rupture in this segment might be extremely severe. Experience borrowed from complex abdominal and thoracoabdominal aneurysm repair demonstrates that fenestrated and branched devices can be deployed safely when anatomical criteria are respected. Elective patients derive the greatest benefit from a fenestrated graft, while urgent cases can be treated confidently with off-the-shelf multibranch systems, reserving other types of repairs for emergent or bail-out cases. While early outcomes of these interventions are promising, it is crucial to acknowledge that limited aortic coverage can still impede effective symptom relief and lead to complications such as aneurysm expansion or rupture. Therefore, further long-term studies are essential to consolidate the technical results and evaluate the durability of various graft options. Full article

Background: Psoriasis is a chronic inflammatory skin disease frequently associated with systemic comorbidities. Human neutrophil peptides 1–3 (HNP1–3), released by neutrophils, have both antimicrobial and proinflammatory effects and may contribute to the pathogenesis of psoriasis and its related conditions. The aim of this study was to evaluate the serum levels of HNP1–3 in patients with psoriasis compared with healthy controls and to assess their association with selected comorbidities and clinical parameters. Methods: In this cross-sectional study, forty-nine patients with psoriasis and forty-nine matched healthy controls were enrolled. Serum HNP1–3 levels were measured using ELISA. Clinical data, including waist-to-hip ratio (WHR), smoking status, and the presence of comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, and pulmonary or autoimmune disorders, were recorded. Results: The mean HNP1–3 levels were significantly higher in the psoriasis patients than in the controls (3.85 ± 0.76 vs. 2.52 ± 0.84 ng/mL; p < 0.001), especially in patients with concomitant PsA (4.21 ± 0.69 ng/mL). Multivariable regression identified increased WHR (β = 1.77, p < 0.01) and smoking (β = 0.45, p < 0.001) as independent predictors of elevated HNP1–3 levels. Positive correlations were also found between HNP1–3 and ESR (r = 0.505, p = 0.019) and IL-6 (r = 0.561, p = 0.008). Conclusions: The elevated serum HNP1–3 levels identified in psoriasis patients—especially those with PsA, central obesity, and smoking history—suggest their potential utility as biomarkers of systemic inflammation. These findings highlight the systemic nature of psoriasis and warrant further research into the clinical utility of HNP1–3 in disease monitoring and risk stratification. Full article

Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity to other pancreatic diseases. At the same time, splenic mesothelial cysts are also rare and typically benign. This report presents a unique case of pancreatic endometriosis coexisting with a splenic mesothelial cyst in a 31-year-old woman. The patient presented to the emergency department with complaints of persistent epigastric and low back pain. She noted having similar symptoms approximately a year prior. Her past medical history was otherwise unremarkable, and there was no known family history of pancreatic disease or neoplasms. Initial imaging revealed a 3.8 cm cystic lesion in the pancreatic tail, with features suggestive of mucinous cystadenoma. Following clinical evaluation and confirmation of the cyst’s nature through endoscopic ultrasound-guided biopsy, the patient subsequently underwent laparoscopic distal pancreatectomy and splenectomy due to worsening symptoms. Gross examination revealed a multilocular pancreatic cyst with a smooth, hemorrhagic wall. Microscopic analysis showed the cyst to be lined by cuboidal to columnar epithelium, consistent with pancreatic endometriosis, confirmed by immunohistochemical staining. The spleen showed cystic formations, diagnosed as a multifaceted mesothelial cyst. In conclusion, this report is the first to document the coexistence of pancreatic endometriosis and splenic mesothelial cysts, highlighting the importance of accurate imaging and pathologic evaluation in the diagnosis of these rare conditions. Early diagnosis and surgical intervention lead to favorable outcomes, reinforcing the importance of comprehensive diagnostic strategies. Full article

Background: Primary vaginal cancer is a rare gynecological condition. We present a case of complete utero-vaginal prolapse complicated by primary invasive vaginal carcinoma. To our knowledge, only a few similar cases have been reported in our region. Case Report: A 77-year-old woman, gravida two and para two, was admitted for treatment of pelvic organ prolapse. The patient reported an eight-year history of uterine bulging but had not used a pessary. The gynecological examination revealed a complete manually irreducible utero-vaginal prolapse with an ulcerative lesion on the right posterolateral vaginal wall. The histological examination diagnosed an HPV-independent keratinizing squamous cell carcinoma, grade I. Comprehensive imaging showed no evidence of metastasis. The patient underwent radical hysterectomy, bilateral adnexectomy, complete resection of the vaginal mass, and pelvic lymphadenectomy. The histopathological examination confirmed clear surgical margins. According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, the disease was classified as stage I vaginal cancer. Postoperatively, the patient received radiotherapy (45 Gy) and high-dose-rate brachytherapy (14 Gy). Conclusions: The co-occurrence of vaginal cancer and utero-vaginal prolapse is exceedingly rare. Surgical intervention followed by radiotherapy is the most common treatment approach. Given the aggressive nature of the disease, comprehensive follow-up is essential. Further research is needed to determine whether long-term genital prolapse increases the risk of vaginal carcinoma. Full article

Background: Oral squamous cell carcinoma (OSCC) is a multifactorial and multistage disease influenced by both genetic susceptibility and environmental risk factors. However, conventional oral cancer preventions are often based on environmental exposures but do not allow for genetic susceptibility and both factors contributing to multistage progressions. This study developed a comprehensive multistate risk model combining both types of factors. Methods: Using data from literature, the researchers built a multistate progression model and calculated transition risks to simulate outcomes in a high-risk population, similar to those eligible for oral cancer screening in Taiwan. Results: The findings showed that OSCC risk varied dramatically across the population, ranging from 362 to over 24,000 cases per 100,000, depending on risk level. The integration of genetic and environmental risk factors into a multistate disease model allows for more accurate risk stratifications of precancerous and invasive OSCC. Frequent screening is more effective, notably in high-risk individuals. Incorporating a health education program provided an additional 2 to 6% reduction in incidence, particularly benefiting higher-risk groups. Simulation findings indicate that tailored screening strategies, particularly when combined with health education interventions, can significantly improve the effectiveness of oral cancer prevention. Conclusions: Quantifying the effects of genetic susceptibility and environmental factors on multistate natural history of precancerous lesions and oral cancer provides a valuable framework for developing the risk-guided policies for oral cancer prevention. Full article

Precision prevention strategies for cervical cancer that integrate genetic biomarkers provide opportunities for personalized risk assessment and optimized preventive measures. An HPV infection–Precancerous–Cancer risk assessment model incorporating genetic polymorphisms and DNA methylation was developed to better understand the regression and progression of cervical lesions by HPV infection status. Utilizing a virtual cohort of 300,000 Taiwanese women aged 30 years and older, our model simulated the natural history of cervical cancer, capturing transitions from a healthy state through precancerous lesions (LSILs and HSILs) to invasive carcinoma and incorporating the possibility of regression between states. Genetic and epigenetic markers significantly influenced disease transitions, demonstrating heterogeneous risks among women with distinct molecular biomarker profiles. Guided by these individual risk profiles, tailored preventive strategies including varying intervals for Pap smear screening, HPV DNA testing, and HPV vaccination showed improved efficiency and effectiveness in reducing cervical cancer incidence compared to uniform approaches. The proposed dynamic transition model of cervical neoplasms incorporating genetic biomarkers can facilitate the development of an individualized risk-based approach for guiding precision prevention towards the goal of cervical cancer elimination. Full article

Lafora progressive myoclonus epilepsy (LD, OMIM#254780, ORPHA:501) is an ultra-rare and severe autosomal recessive neurological disorder that typically manifests in early adolescence. It is characterized by the accumulation of insoluble forms of aberrant glycogen in the brain and peripheral tissues. Given the urgent need for reliable tools to monitor disease progression, we aimed to identify reliable biomarkers in minimally invasive fluids, which could also provide valuable insights into the natural history of the disease. Plasma-EDTA samples from eleven LD patients and healthy controls were analyzed to identify potential biomarkers of LD using a high-throughput assay. The findings were subsequently validated using specific enzyme-linked immunosorbent assays (ELISAs). Eleven cytokines and growth factors were identified to be significantly reduced in LD patient samples compared to healthy controls. Among these, four mediators [platelet-derived growth factor subunit B (PDGF-BB), epidermal growth factor (EGF), brain derived growth factor (BDNF), and macrophage migration inhibitory factor (MIF)] exhibited the greatest fold change between the groups and were further validated. Given the minimally invasive nature of plasma sampling and the straightforward quantification via ELISA assays, these biomarkers hold strong promise for rapid translation to the clinic, potentially enhancing early diagnosis and longitudinal disease monitoring in LD patients. Full article