BioMed, Volume 5, Issue 4 (December 2025) – 6 articles

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574. Full article

Background and Clinical Significance: Primary Cutaneous Cribriform Apocrine Carcinoma (PCCAC) is a rare, inert low-grade cutaneous malignancy that is diagnosed on histopathologic assessment. PCCAC usually presents in middle-aged adults as a solitary, subcutaneous nodule on the extremities. Characterized by anastomosing tubules and solid/cribriform nests of atypical epithelial cells generating a sieve-like display, the tumor is a histopathological variant of apocrine metaplasia of the skin. PCCAC also follows characteristic staining patterns. It is important to distinguish PCCAC from other similar histological variants, which may hold more grievous indications. Case Presentation: A 47-year-old female presented with an enlarging, itchy growth of several months on her back. On physical exam, an indurated pink, nontender papule of 8 mm on the left lateral side wall was noted. Histopathology demonstrated a well-circumscribed, pandermal tumor composed of anastomosing solid and cribriform nests, tubules, and cords of mildly atypical, eosinophilic epithelial cells forming a glandular lumina. An immunohistochemical study revealed the tumoral epithelium to express CK7, CK5/6, BER-EP4, CD117 (C-kit), and S100. Positive EMA and CEA staining highlighted intratumoral glandular ductal differentiation and apocrine secretion. Immunohistochemical stains for CK20, GATA-3, and p63 were negative. Conclusions: We present this case to distinguish the histological attributes of PCCAC and help differentiate it from more concerning visceral metastatic malignancies. We follow with a narrative review of the histopathologic differential for PCCAC and feature reconciliation of corresponding staining patterns reported in the literature. Full article

Background/Objectives: Bacteriophages are considered promising alternatives for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. Methods: Five bacteriophages with lytic activity against MDR P. aeruginosa were isolated from lake and sewage samples and characterized for their biological properties, host range, and efficacy in biofilm and in vitro infection models. Results: The phages displayed broad host ranges, producing zones of lysis in 40–53% of MDR isolates. The average burst size was 112 ± 70 PFU per cell. All phages, either individually or in combination, inhibited biofilm formation and were capable of disrupting preformed biofilms. While treatment with single phages led to bacterial regrowth, the cocktail of all five phages achieved complete bacterial lysis with no regrowth observed. In an in vitro wound and burn infection model, the phage cocktail significantly enhanced cell proliferation and promoted healing. Transmission electron microscopy (TEM) analysis identified phage PA2 as a Myovirus based on its morphology. Conclusions: The phage isolates demonstrated strong activity in multiple in vitro models, effectively targeting both planktonic and biofilm-associated P. aeruginosa. Notably, the five-phage combination prevented the emergence of bacterial resistance, supporting its potential as a biocontrol strategy against MDR P. aeruginosa. Full article

Background and objectives: Clinical laboratory analyses are essential for diagnosing and treating allergic diseases mediated by immunoglobulin E (IgE). Identifying the sources of sensitivity, subject to regional variations, enables the implementation of effective management strategies, such as prevention and immunotherapy. Through a cross-sectional study, this study aimed to determine the sensitivity profile to aeroallergens (latent class) and their correlation with age, sex, and season in the population sampled. Methods: The purpose was to map the concentrations of specific IgE serum levels linked to the most prevalent allergens, considering variations related to age, specific IgE levels, and seasons of the year through a cross-sectional study. Results: The 995 reports of specific IgE tests analyzed were clustered into six aeroallergen categories and were predominantly composed of female individuals (57.1%). The most prevalent age group was younger than 18 (56.5%), and most exams were performed in the spring (27.7%). The aeroallergen category ‘grass’ significantly correlated with sex and age, indicating that men have a 65% greater probability of having high levels of specific IgE as a response to this allergen, and age is related to higher IgE levels. Latent class analysis identified an optimal three-class solution for specific IgE sensitization patterns: Class 1: Moderate Sensitization; Class 2: Low Sensitization; and Class 3: High Sensitization. Conclusion: The present study highlights the importance of knowing the local aeroallergen profile for early diagnosis and prevention of allergic diseases, emphasizing the relevance of the allergen category related to the age and sex of the individuals. Full article

Background/Objectives: Chronic ankle instability is a common issue after lateral ankle sprain. The DMA Clinical Pilates method hypothesizes impairments in tibialis anterior and fibularis longus muscles. Methods: A total of 14 adults with chronic ankle instability, and 15 recovered and 16 healthy individuals were prospectively recruited and assessed for lower back, hip, knee, and ankle muscle activities during dominant and non-dominant sides single-leg stand on stable and unstable surfaces using wireless surface electromyography. Results: The study found consistent dysfunction in tibialis anterior muscle activity in adults with chronic ankle instability when compared with healthy adults during single-leg stand on stable and unstable surfaces, and against recovered individuals on unstable surface. As compared to healthy controls, chronic ankle instability group showed higher vastus lateralis activation during dominant side single-leg stand across surface conditions and during dominant side single-leg stand, while the higher dominant side longissimus dorsi activity on stable surface changed to higher dominant side medial gastrocnemius activity on unstable surface. As compared to recovered controls, chronic ankle instability group also showed higher gluteus medius and fibularis longus muscle activities on unstable surface. Conclusions: Tibialis anterior muscle is the main dysfunction among individuals with chronic ankle instability side. Full article

Background/Objectives: Black hairy tongue syndrome (BHT) is characterized by structural epithelial changes and a dark discoloration on the surface of the tongue, causing a variety of symptoms such as xerostomia, altered taste, and nausea. Methods: Herein, we report a 70-year-old female patient with a history of Sjogren’s syndrome, rheumatoid arthritis, and occasional use of intranasal and inhaled corticosteroids, who presented with BHT exacerbated by consumption of colored beverages and carbohydrates. We also provide a review of the literature on published articles reporting cases of BHT syndrome. Results: Our patient’s condition improved after implementing dietary restrictions in combination with local care. A literature review revealed that the most common reported exposures and underlying conditions in patients with BHT were the recent administration of antibiotics, solid organ or hematologic malignancy, immunosuppressants, smoking, corticosteroids, autoimmune conditions, receipt of antidepressants, local radiation therapy, proton pump inhibitors, and alcohol. The majority of cases were successfully managed with the elimination of implicated factors when possible and local hygiene. Conclusions: Different factors may contribute to the development of BHT. Discontinuation of implicated medications together with measures for topical care constitute the most effective ways to achieve resolution. Full article