BiomedicinesPub Date : 2025-08-08DOI: 10.3390/biomedicines13081936
Giulia Pignataro, Cristina Triunfo, Andrea Piccioni, Simona Racco, Mariella Fuorlo, Evelina Forte, Francesco Franceschi, Marcello Candelli
{"title":"The Epigenetics of Sepsis: How Gene Modulation Shapes Outcomes.","authors":"Giulia Pignataro, Cristina Triunfo, Andrea Piccioni, Simona Racco, Mariella Fuorlo, Evelina Forte, Francesco Franceschi, Marcello Candelli","doi":"10.3390/biomedicines13081936","DOIUrl":"https://doi.org/10.3390/biomedicines13081936","url":null,"abstract":"<p><p>Sepsis is a complex and heterogeneous condition, arising from a disrupted immune response to infection that can progress to organ failure and carries a high risk of death. In recent years, growing attention has been paid to the role of epigenetic mechanisms-including DNA methylation, histone modifications, non-coding RNAs, and RNA methylation-in shaping immune activity during sepsis. These processes affect immune functions such as macrophage polarization, cytokine release, and the exhaustion of immune cells, and they help explain the shift from an initial phase of overwhelming inflammation to a later state of immune suppression. Epigenetic alterations also contribute to tissue-specific damage, notably in the lungs, kidneys, and heart, and have been linked to disease severity and clinical prognosis. Advances in transcriptomic and epigenetic profiling have made it possible to distinguish molecular subtypes of septic patients, each with distinct immune features and varied responses to treatments such as corticosteroids and metabolic therapies. Emerging biomarkers-like AQP5 methylation, histone lactylation (H3K18la), and m<sup>6</sup>A RNA methylation-are opening new options for patient classification and more tailored therapeutic strategies. This review examines the current understanding of how epigenetic regulation contributes to the pathophysiology of sepsis and considers its implications for developing more individualized approaches to care.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-08DOI: 10.3390/biomedicines13081945
María Rosado-Sanz, Nuria Martínez-Alarcón, Adrián Abellán-Soriano, Raúl Golfe, Eva M Trinidad, Jaime Font de Mora
{"title":"Cytokine Networks in Triple-Negative Breast Cancer: Mechanisms, Therapeutic Targets, and Emerging Strategies.","authors":"María Rosado-Sanz, Nuria Martínez-Alarcón, Adrián Abellán-Soriano, Raúl Golfe, Eva M Trinidad, Jaime Font de Mora","doi":"10.3390/biomedicines13081945","DOIUrl":"https://doi.org/10.3390/biomedicines13081945","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) remains a challenging subtype of breast cancer due to its aggressive nature and lack of targeted therapies. Cytokines play a pivotal role in shaping the tumor microenvironment, modulating tumor progression, immune evasion, and therapy resistance. In this review, we discuss the complex cytokine networks involved in TNBC biology, highlighting their contribution to key oncogenic processes, including proliferation, angiogenesis, epithelial-mesenchymal transition, and immunomodulation. We also summarize current and emerging cytokine-targeted therapeutic strategies, including monoclonal antibodies, bispecific antibodies, cell-based therapies, and cytokine-armed CAR-T and CAR-NK cell approaches, with a focus on clinical implications and future directions.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-08DOI: 10.3390/biomedicines13081934
Matteo Daverio, Mariaenrica Tinè, Umberto Semenzato, Roberta Prevedello, Matteo Dalla Libera, Elisabetta Cocconcelli, Elisabetta Balestro, Marco Damin, Paolo Spagnolo, Davide Biondini
{"title":"Non-Specific Pleuritis After Medical Thoracoscopy: The Portrait of an Open Issue and Practical Hints for Its Management.","authors":"Matteo Daverio, Mariaenrica Tinè, Umberto Semenzato, Roberta Prevedello, Matteo Dalla Libera, Elisabetta Cocconcelli, Elisabetta Balestro, Marco Damin, Paolo Spagnolo, Davide Biondini","doi":"10.3390/biomedicines13081934","DOIUrl":"https://doi.org/10.3390/biomedicines13081934","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Up to one third of pleural biopsies performed during medical thoracoscopy (MT) are labelled as non-specific pleuritis (NSP). The histological diagnosis of NSP has long been worrisome for pulmonologists, with the potential to evolve into a life-threatening condition. The aim of this study was to identify clinical and biological predictors for patients with a diagnosis of NSP to guide clinical decisions. <b>Methods</b>: Baseline, procedural and follow-up data of NSP patients were retrospectively analysed to identify potential outcome predictors. <b>Results</b>: Of the 272 patients who underwent MT, 192 (71%) were diagnosed with malignancies, 9 (3%) with benign diseases and 71 (26%) with NSP. At follow-up, 17% were diagnosed with malignant disease and 21% with a benign condition and 62% remained idiopathic. A thoracoscopist's evaluation of the pleural appearance reported a PPV of 28% and an NPV of 91% to predict malignancy. Patients with a subsequent diagnosis of malignancy tended to have a higher volume of fluid drained than those with persistently idiopathic NSP [2.7 litres (L) vs. 1.6 L <i>p</i> = 0.06]. A lymphocytic pleural effusion was more common in the malignant and idiopathic groups (63% and 60%, respectively) than the benign group (16%; <i>p</i> = 0.06 and <i>p</i> = 0.01). The three groups had a similar rate of effusion recurrence. Overall survival was higher in patients with idiopathic pleural effusion than in those with malignant (<i>p</i> = 0.04) or benign disease (<i>p</i> = 0.008). <b>Conclusions</b>: NSP diagnosis hides a malignancy in one in five cases, underlying the importance of closely following up these patients. The volume of drained pleural fluid, cell count and thoracoscopist's impression may guide clinicians in the challenging management of patients with NSP.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-08DOI: 10.3390/biomedicines13081937
Federica Arzilli, Giulia De Fortuna, Ignazio Cammisa, Luca Vagnozzi, Giorgio Sodero, Donato Rigante, Clelia Cipolla
{"title":"Diagnostic Challenges of Short Stature and Growth Hormone Insufficiency Across Different Genetic Etiologies.","authors":"Federica Arzilli, Giulia De Fortuna, Ignazio Cammisa, Luca Vagnozzi, Giorgio Sodero, Donato Rigante, Clelia Cipolla","doi":"10.3390/biomedicines13081937","DOIUrl":"https://doi.org/10.3390/biomedicines13081937","url":null,"abstract":"<p><p><b>Background</b>: Recent advances in genetic research have significantly expanded our understanding of the molecular bases of growth hormone deficiency (GHD), and numerous genes have been identified as impacting final stature through isolated or combined abnormalities of growth hormone (GH), GH insensitivity, and insulin growth factor-1 (IGF-I) resistance. <b>Objective</b>: This review summarizes the current knowledge on the genetic causes of GHD in the context of pediatric short stature, emphasizing the role of next-generation sequencing technologies in real-life clinical practice and the potential impact of genetic diagnosis over therapeutic decisions regarding GH replacement therapy. <b>Materials and methods</b>: Articles from PubMed up to April 2025 dealing with GHD were retrieved and analyzed, focusing on genes influencing the GH pathway and stunted growth, with focused attention on relevant molecular and clinical studies. <b>Results</b>: Our analysis, besides cataloguing well-established and novel contributors to growth failure among genes associated with the GH-IGF1 axis, also emphasizes the crucial role of genetic testing and strategies that should be used to maximize the likelihood of identifying a specific genetic etiology, such as prioritizing genetic tests when a monogenic cause is strongly suspected or when there are peculiar clinical features that could be linked to specific genetic conditions. <b>Conclusions</b>: We have highlighted the most recent genetic etiologies of short stature related to GHD, providing an updated framework that is expected to be helpful in the diagnostic and therapeutic management of individuals with mutations related to the GH-IGF1 axis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice.","authors":"Chenzhao He, Guibo Qi, Xin He, Wenwei Shao, Chao Ma, Zhangfan Wang, Haochuan Wang, Yuntong Tan, Li Yu, Yongsheng Xie, Song Qin, Liang Chen","doi":"10.3390/biomedicines13081943","DOIUrl":"https://doi.org/10.3390/biomedicines13081943","url":null,"abstract":"<p><p><b>Background</b>: The red nucleus (RN) is a phylogenetically conserved structure within the midbrain that is traditionally associated with general motor coordination; however, its specific role in controlling directional movement remains poorly understood. <b>Methods</b>: This study systematically investigates the function and mechanism of RN neurons in directional movement by combining stereotactic brain injections, fiber photometry recordings, multi-unit in vivo electrophysiological recordings, optogenetic manipulation, and anterograde trans-synaptic tracing. <b>Results</b>: We analyzed mice performing standardized T-maze turning tasks and revealed that anatomically distinct RN neuronal ensembles exhibit direction-selective activity patterns. These neurons demonstrate preferential activation during ipsilateral turning movements, with activity onset consistently occurring after movement initiation. We establish a causal relationship between RN neuronal activity and directional motor control: selective activation of RN glutamatergic neurons facilitates ipsilateral turning, whereas temporally precise inhibition significantly impairs the execution of these movements. Anterograde trans-synaptic tracing using H129 reveals that RN neurons selectively project to spinal interneuron populations responsible for ipsilateral flexion and coordinated limb movements. <b>Conclusions</b>: These findings offer a framework for understanding asymmetric motor control in the brain. This work redefines the RN as a specialized hub within midbrain networks that mediate lateralized movements and offers new avenues for neuromodulatory treatments for neurodegenerative and post-injury motor disorders.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-07DOI: 10.3390/biomedicines13081925
María Alexandra Bedoya, Gloria Cristina Moreno, Camilo Durán, Adriana Camacho, Angel Eduardo Pirela, Stefany Rojas Lozano, Maddy Mejía, Eddy Herrera, Luz-Stella Rodríguez Camacho, Lorenza Jaramillo, Nelly S Roa
{"title":"Mechanically Induced Pulpitis: A Rat Model That Preserves Animal Well-Being.","authors":"María Alexandra Bedoya, Gloria Cristina Moreno, Camilo Durán, Adriana Camacho, Angel Eduardo Pirela, Stefany Rojas Lozano, Maddy Mejía, Eddy Herrera, Luz-Stella Rodríguez Camacho, Lorenza Jaramillo, Nelly S Roa","doi":"10.3390/biomedicines13081925","DOIUrl":"https://doi.org/10.3390/biomedicines13081925","url":null,"abstract":"<p><p><b>Background</b>: Understanding the mechanisms underlying dental pain caused by pulpitis in humans has led to the development of animal models, such as the rat, which enable the study of the mechanisms underlying inflammation; the use of these models is considered ethically justified when the anticipated scientific benefits outweigh the potential impacts on animals in the harm/benefit balance. <b>Objective</b>: To develop a rat model of mechanically induced pulpitis and to evaluate the potential impact on animal well-being. <b>Methods:</b> Pulpitis was mechanically induced in male Lewis rats (13-16 weeks, 350-400 g) which were anesthetized and endotracheally intubated. Following pulp exposure, the cavity was sealed with either amalgam (n = 10) or zinc phosphate cement (n = 10). Following recovery and return to their housing, behavioral assessments and histological evaluations using Hematoxylin and Eosin (H&E) staining were conducted in separate cohorts at two time points: 3 h and 5 days following the procedure. <b>Results</b>: A standardized model of mechanically induced pulpitis was established and verified clinically and by histopathological analysis, which showed evidence of the inflammatory process and revealed no statistically significant differences in the scoring of pain, discomfort, or distress, nor in the measurements of food and water consumption or body weight. <b>Conclusions</b>: The behavioral assessments conducted in this study supported the implementation of a safe and easily reproducible model for future research aimed at elucidating the mechanisms underlying pulp inflammation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-07DOI: 10.3390/biomedicines13081923
Iris Otero Luis, Alicia Saz-Lara, Arturo Martinez-Rodrigo, María José Rodríguez-Sánchez, María José Díaz Valentín, María José Simón Saiz, Rosa María Fuentes Chacón, Iván Cavero Redondo
{"title":"Effect of Remote Ischemic Preconditioning Evaluated by Nurses on Improvement of Arterial Stiffness, Endothelial Function, Diastolic Function, and Exercise Capacity in Patients with Heart Failure with Preserved Ejection Fraction (PIRIC-FEp Study): Protocol for Randomised Controlled Trial.","authors":"Iris Otero Luis, Alicia Saz-Lara, Arturo Martinez-Rodrigo, María José Rodríguez-Sánchez, María José Díaz Valentín, María José Simón Saiz, Rosa María Fuentes Chacón, Iván Cavero Redondo","doi":"10.3390/biomedicines13081923","DOIUrl":"https://doi.org/10.3390/biomedicines13081923","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Heart failure with preserved ejection fraction (HFpEF) has increased in prevalence as the population ages and associated comorbidities increase. Remote ischemic preconditioning (RIPC) has been shown to provide protection against ischemic injury to the heart and other organs. Therefore, the aim of this project will be to analyse the effectiveness of RIPC in terms of arterial stiffness, endothelial function, diastolic function, and exercise capacity in patients with HFpEF. <b>Methods</b>: The PIRIC-FEp study will be a parallel, randomised controlled trial with two groups conducted at the Faculty of Nursing in Cuenca, University of Castilla-La Mancha. Individuals who are diagnosed with HFpEF and are older than 40 years, with a left ventricular ejection fraction ≥50% and a sedentary lifestyle, will be included. The exclusion criteria will include, among others, patients with noncardiac causes of heart failure symptoms, significant pulmonary disease, diabetes, peripheral vascular disease, or myocardial infarction within the previous three months. A sample size of 48 patients was estimated, with 24 for each group. Participants will be randomly allocated (1:1) to either the RIPC intervention group or the control group to evaluate the effects on arterial stiffness, endothelial function, diastolic function, and exercise capacity. Assessments will be conducted at baseline and after a three-month follow-up period. <b>Results</b>: The findings will be published in a peer-reviewed journal article. <b>Conclusions</b>: This study is important for daily clinical practice because it provides a new approach for the treatment of HFpEF patients via RIPC.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-07DOI: 10.3390/biomedicines13081929
Jae Heon Kim, Hoonhee Seo, Sukyung Kim, Md Abdur Rahim, Sujin Jo, Indrajeet Barman, Hanieh Tajdozian, Faezeh Sarafraz, Md Sarower Hossen Shuvo, Ho-Yeon Song, Yun Seob Song
{"title":"Association of Intratumoral Microbiota Modulation with Prostate Cancer Progression: A Microbiome Analysis of Prostatic Tissue.","authors":"Jae Heon Kim, Hoonhee Seo, Sukyung Kim, Md Abdur Rahim, Sujin Jo, Indrajeet Barman, Hanieh Tajdozian, Faezeh Sarafraz, Md Sarower Hossen Shuvo, Ho-Yeon Song, Yun Seob Song","doi":"10.3390/biomedicines13081929","DOIUrl":"https://doi.org/10.3390/biomedicines13081929","url":null,"abstract":"<p><p><b>Background:</b> The involvement of the intratumoral microbiome in prostate cancer progression is becoming increasingly acknowledged. This study analyzed the microbiome of prostate cancer tissues from patients with localized prostate cancer (LPC, stages 1-2) and advanced prostate cancer (APC, stages 3-4) to determine its association with cancer progression. <b>Methods:</b> Paraffin-embedded tissue samples obtained during radical prostatectomy underwent 16S rRNA amplicon-based profiling. <b>Results:</b> The profile of the bacterial communities in LPC and APC differed remarkably. While species diversity remained stable, species richness (as determined by the ACE analysis) was significantly lower in APC, correlating with a decrease in <i>Enhydrobacter</i> (which is more abundant in LPC) and an increase in <i>Lautropia</i> (enriched in APC). The role of <i>Lautropia</i> in the progression of cancer was confirmed by in vitro studies employing cell lines from prostate cancer. <b>Conclusions:</b> These findings demonstrate the potential of microbiome-targeted interventions in the management of prostate cancer.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-07DOI: 10.3390/biomedicines13081928
Tamara Knezevic Ivanovski, Marija Milic Perovic, Bojan Stopic, Olga Golubovic, Djordje Kralj, Milos Mitrovic, Slobodan Sreckovic, Ana Dobrosavljevic, Petar Svorcan, Srdjan Markovic
{"title":"Is Deep Remission the Right Time to De-Escalate Biologic Therapy in IBD? A Single-Center Retrospective Study.","authors":"Tamara Knezevic Ivanovski, Marija Milic Perovic, Bojan Stopic, Olga Golubovic, Djordje Kralj, Milos Mitrovic, Slobodan Sreckovic, Ana Dobrosavljevic, Petar Svorcan, Srdjan Markovic","doi":"10.3390/biomedicines13081928","DOIUrl":"https://doi.org/10.3390/biomedicines13081928","url":null,"abstract":"<p><p><b>Background and Aim</b>: Long-term treatment with biologic therapy alongside immunomAfodulators in patients with inflammatory bowel disease (IBD) can be associated with severe side effects. The objective of this study was to determine whether discontinuing anti-TNF treatment after two years in patients who have achieved mucosal healing is associated with lower relapse rates. <b>Materials and Methods</b>: A total of 67 patients with IBD from a single tertiary IBD Center who had achieved mucosal healing were enrolled in this retrospective study. In this single-center retrospective study (January 2014-December 2022), we screened 67 IBD patients in deep remission (endoscopic mucosal healing after ≥2 years of anti-TNF therapy). After excluding three patients without histologic data, 64 patients (25 ulcerative colitis, 39 Crohn's disease) were analyzed. Mayo endoscopic sub-score and SES-CD were used to evaluate endoscopic activity after two years of anti-TNF therapy. Histological activity was assessed using the GHAS (for CD) and Nancy index (for UC). <b>Results</b>: A total of 67 patients were screened, of whom 3 were excluded due to a lack of biopsies. Of the 64 included patients, 39.06% (25/64) had UC and 60.9% (39/64) had CD, with a mean disease duration of 11.6 ± 8.0 years. All patients were in endoscopic remission at the time of therapy de-escalation, and 60.9% (39/64) also achieved histological remission (\"deep remission\"). In the follow-up of 38.6 months (IQR 30-48) after biologic therapy was stopped, 57.8% (37/64) relapsed with a median time to relapse of 13.5 months (IQR 8-24) off anti-TNF-a total of 34 patients required a restarting of biologic therapy. Using Spearman's correlation, a moderate connection was observed between histological activity at withdrawal and subsequent relapse (rho = 0.467, <i>p</i> < 0.001). The probability of relapsing within 4 years after anti-TNF cessation was significantly higher (OR 2.72) in patients with histologically active disease at the time of de-escalation. <b>Conclusions</b>: Achieving 'deep remission' (clinical, endoscopic, and histological healing) may be a suitable parameter for making decisions on when to de-escalate therapy; however, given that over half of patients in endoscopic remission relapse after discontinuation, any de-escalation should be approached with caution and individualized patient assessment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomedicinesPub Date : 2025-08-06DOI: 10.3390/biomedicines13081918
Liat Gantz, Avi Besser, Rivki Bloom, Reut Ifrah
{"title":"Functional and Emotional Impact of Dry Eye and Meibomian Gland Dysfunction in Keratoconus.","authors":"Liat Gantz, Avi Besser, Rivki Bloom, Reut Ifrah","doi":"10.3390/biomedicines13081918","DOIUrl":"https://doi.org/10.3390/biomedicines13081918","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Dry eye (DE) can cause persistent eye rubbing, contributing to keratoconus (KC) development and progression. Both keratoconus (KC) and dry eye (DE) significantly impact patients' functional and emotional well-being, with KC patients exhibiting a higher prevalence of DE symptoms and signs. This study examined whether functional (KEPAQ-F) and emotional (KEPAQ-E) quality of life, assessed by the Keratoconus End-Points Assessment Questionnaire, differ when influenced by symptoms and clinical signs of general DE versus meibomian gland dysfunction (MGD) in KC patients. <b>Methods</b>: Volunteers with KC (ages 18-70) underwent DE and MGD assessments, completing OSDI, MGD (MGDQ), and KEPAQ questionnaires. Clinical measures included NITBUT, Schirmer, and meibography. Pearson correlations and path analysis assessed relationships between DE and MGD symptoms and KEPAQ-F/E. <b>Results</b>: Forty-five KC participants (mean age: 45 ± 13, range: 20-69 years, 25 males) were enrolled; 22 (49%) had DE, and 15 (33%) had MGD. Significant correlations were observed between KEPAQ-E (2.9 ± 3.0 Logit) and KEPAQ-F (1.7 ± 3.0 Logit) scores with OSDI (26.5 ± 26.7) and MGDQ (3.3 ± 2.2) scores, and all Belin outcome measures A-D for all participants. In participants with diagnosed dry eye, KEPAQ E and F were also significantly correlated with loss of meibomian glands in the lower eyelids (R = -0.44, <i>p</i> = 0.04). Path analysis showed both DE and MGD were negatively correlated with lower KEPAQ-E and KEPAQ-F scores, with DE symptoms more influential (<i>p</i> < 0.05). The model explained 42% of the KEPAQ-E variance and 41% of the KEPAQ-F variance. <b>Conclusions</b>: Emotional and functional quality of life in KC is significantly and negatively related to DE and MGD symptoms, with DE symptoms exhibiting a greater impact. Furthermore, greater loss of meibomian glands in the lower eyelids is significantly associated with reduced emotional and functional KEPAQ scores in DE patients. These results underscore the critical importance of evaluating DE in KC to improve patient-reported outcomes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 8","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12384006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}