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16 pages, 1416 KB  
Review
Best Practices for the Nutritional Management of Infantile-Onset Lysosomal Acid Lipase Deficiency: A Case-Based Discussion
by Fiona J. White, Javier de las Heras, Celia Rodríguez-Borjabad, Simon A. Jones, Alexander Y. Kim, Jenna Moore, Florian Abel, Laura Frank, Rosie Jones and Suresh Vijay
Nutrients 2026, 18(2), 233; https://doi.org/10.3390/nu18020233 - 12 Jan 2026
Viewed by 158
Abstract
Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads [...] Read more.
Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. Full article
(This article belongs to the Section Pediatric Nutrition)
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14 pages, 2867 KB  
Article
Efficacy of Modified Talc Powder in Experimental Rat Model of Pleurodesis
by Murat Kilic, Onural Ozhan, Azibe Yildiz, Süleyman Koytepe, Mustafa Akyuz, Yusuf Turkoz, Nurcan Gokturk, Merve Biyikli, Rumeysa Sonmez, Idil Karaca Acari and Hakan Parlakpinar
Biomolecules 2026, 16(1), 104; https://doi.org/10.3390/biom16010104 - 7 Jan 2026
Viewed by 272
Abstract
Background: Pleurodesis is a treatment method that aims to create permanent adhesion between the pleural layers to prevent recurrent fluid or air accumulation in the pleural cavity. Talc, one of the most commonly preferred agents in this procedure, is widely used in clinical [...] Read more.
Background: Pleurodesis is a treatment method that aims to create permanent adhesion between the pleural layers to prevent recurrent fluid or air accumulation in the pleural cavity. Talc, one of the most commonly preferred agents in this procedure, is widely used in clinical practice. In this study, a new talc formulation with a modified surface to impart antibacterial and analgesic properties was experimentally evaluated for the first time. The main objective of the study was to comparatively assess the inflammatory and fibrotic responses following standard talc and modified talc applications. Methods: Thirty-six 12-week-old female Wistar albino rats were simply randomly divided into three different groups: control (n = 12), standard talc (n = 12), and modified talc (n = 12). Under anesthesia, 1 mL of physiological saline containing 17 mg of talc was injected intrapleurally into the right hemithorax. The presence of pneumothorax after the procedure was assessed by chest radiography. After a 12-day follow-up period, the animals were euthanized. Bronchoalveolar lavage (BAL) fluid samples, blood samples, and lung and pleural tissue samples were collected for biochemical, histopathological, and immunohistochemical analyses. Results: Modified talc application resulted in a significant increase in both visceral and parietal pleural thickness (p < 0.05). Granulation tissue formation and collagen deposition were significantly higher in the modified talc group. In addition, TGF-β expression and CD68-positive macrophage count increased significantly in the modified talc group (p < 0.05). Inflammatory changes in the lung parenchyma were limited and not statistically significant. Conclusions: The modified talc formulation enriched with lidocaine and antibacterial agents produced a stronger inflammatory and fibrotic response compared to standard talc. These findings indicate that modified talc may increase the effectiveness of pleurodesis. Furthermore, the absence of significant lung parenchymal damage suggests that this treatment is locally effective and feasible. However, further long-term and advanced studies are needed to translate these results into clinical use. Full article
(This article belongs to the Section Bio-Engineered Materials)
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24 pages, 2728 KB  
Review
Circulating Fibrocytes: Cellular Mediators of Tissue Fibrosis
by Xinya Guo, Jianyu Lu, Yiyao Du, Zhaofan Xia and Shizhao Ji
Int. J. Mol. Sci. 2026, 27(2), 557; https://doi.org/10.3390/ijms27020557 - 6 Jan 2026
Viewed by 213
Abstract
Fibrosis is a pathological condition resulting from an excessive tissue response during the repair process, often affecting various tissues such as the skin, organs, and joints, posing a significant threat to global health. Researchers have made substantial efforts to explore the endogenous mechanisms [...] Read more.
Fibrosis is a pathological condition resulting from an excessive tissue response during the repair process, often affecting various tissues such as the skin, organs, and joints, posing a significant threat to global health. Researchers have made substantial efforts to explore the endogenous mechanisms underlying fibrosis in recent years and have developed several therapeutic strategies to block this process. Historically, research on fibrotic diseases has focused on identifying highly relevant therapeutic targets and developing effective antifibrotic drugs. However, due to the complexity of the mechanisms of fibrosis and its effector cells, the effectiveness of antifibrotic therapies remains limited. With the advancement of high-throughput omics technologies and machine learning tools, we now have a clearer understanding of cellular heterogeneity, intercellular interactions, and the specific roles of cells in various biological processes. This enables tracking the trajectory of different cell types during the fibrotic process, facilitating early identification and discovery of new targets for fibrosis treatment, and conducting more precise targeted research. Supported by these novel technologies, numerous studies have revealed that, in addition to normal fibroblasts, a group of bone marrow–derived fibrocytes also contributes to the fibrosis of both parenchymal and non-parenchymal organs and tissues. Circulating fibrocytes are hematopoietic-derived cells that are recruited to injury sites during injury, disease, and aging, acting as participants in inflammation and tissue repair, and directly or indirectly promoting fibrosis in various tissues throughout the body. This review summarizes the general characteristics of circulating fibrocytes, the molecular mechanisms involved in their recruitment to different tissues, the process of their differentiation into fibroblasts, their potential roles in various diseases, and the latest research developments in this field. Given the key role of circulating fibrocytes in fibrosis across multiple tissues, they may serve as promising targets for the development of novel antifibrotic therapies. Full article
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15 pages, 385 KB  
Article
Association of Endothelial Activation and Stress Index with Prognosis in Posterior Circulation Infarcts Treated with Recanalization Therapy
by Deniz Kamaci Sener, Cemile Haki, Gulcin Koc Yamanyar, Fatma Nur Kandemir, Suat Kamisli and Kaya Sarac
Diagnostics 2025, 15(24), 3234; https://doi.org/10.3390/diagnostics15243234 - 17 Dec 2025
Viewed by 301
Abstract
Background: Endothelial dysfunction plays a critical role in ischemic stroke. The Endothelial Activation and Stress Index (EASIX), calculated from creatinine, lactate dehydrogenase (LDH), and platelet levels, reflects endothelial injury. This study aimed to investigate the relationship between EASIX and 90-day mortality in [...] Read more.
Background: Endothelial dysfunction plays a critical role in ischemic stroke. The Endothelial Activation and Stress Index (EASIX), calculated from creatinine, lactate dehydrogenase (LDH), and platelet levels, reflects endothelial injury. This study aimed to investigate the relationship between EASIX and 90-day mortality in patients with posterior circulation ischemic stroke (PCIS) treated with mechanical thrombectomy. Methods: Fifty-eight patients with acute ischemic stroke who underwent mechanical thrombectomy (MT) or MT combined with intravenous thrombolysis (intravenous tissue plasminogen activator (tPA)) for posterior circulation ischemic stroke (PCIS) were included. EASIX was calculated using 24 h laboratory values of creatinine, LDH, and platelets. Its association with 90-day mortality, length of hospital stay, intubation, and parenchymal hemorrhage was analyzed. Results: In patients receiving reperfusion therapy, the Endothelial Activation and Stress Index (EASIX) showed modest ability to predict 90-day mortality (AUC = 0.583, 95% CI 0.428–0.739, p = 0.295). Higher EASIX values were linked to a 6.58-fold increase in mortality risk. Patients with elevated EASIX were generally older, had more frequent hyperlipidemia, had higher 24 h National Institutes of Health Stroke Scale (NIHSS) scores, had greater need for intubation, and had higher in-hospital mortality. Conclusions: EASIX is a simple, inexpensive, and non-invasive marker that may reflect endothelial dysfunction and help predict mortality in PCIS patients undergoing reperfusion therapy. Higher EASIX values are associated with poorer prognosis. Early identification of high-risk patients may support secondary prevention strategies. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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15 pages, 3021 KB  
Article
Multiparametric MRI Markers Associated with Breast Cancer Risk in Women with Dense Breasts
by Wesley Surento, Romy Fischer, Debosmita Biswas, Daniel S. Hippe, Anum S. Kazerouni, Jin You Kim, Isabella Li, John H. Gennari, Habib Rahbar and Savannah C. Partridge
Cancers 2025, 17(23), 3771; https://doi.org/10.3390/cancers17233771 - 26 Nov 2025
Viewed by 552
Abstract
Background/Objectives: This study explored the associations of normal breast tissue characteristics on multiparametric MRI with clinical assessments of breast cancer risk in women with dense breasts. Methods: Women with dense breasts who underwent multiparametric MRI were included. Breast cancer risk was [...] Read more.
Background/Objectives: This study explored the associations of normal breast tissue characteristics on multiparametric MRI with clinical assessments of breast cancer risk in women with dense breasts. Methods: Women with dense breasts who underwent multiparametric MRI were included. Breast cancer risk was determined based on Tyrer–Cuzick (TC) lifetime risk scores, categorized as high (TC ≥ 20%) or low risk. Qualitative background parenchymal enhancement (BPE) assessment was obtained from imaging reports. Quantitative imaging markers were calculated, including median BPE, median apparent diffusion coefficient, and volume measures of the whole breast, fibroglandular tissue (FGT), blood vessels, and BPE regions. The associations between imaging markers and TC risk groups were evaluated using age-adjusted logistic regression and summarized by area under the receiver operating characteristic curve (AUC). Results: Seventy-seven women were evaluated; a total of 20 (26%) were low risk, and 57 (74%) were high risk. After adjusting for age and multiple testing, BPE:breast ratio (adj. p = 0.037), FGT:breast ratio (adj. p = 0.046), and BPE:vessel ratio (adj. p = 0.037) were positively associated with risk, while qualitative BPE was not (adj. p = 0.11). Overall, risk categorizations based on imaging markers were concordant with TC score in up to 70% of women. Conclusions: In women with dense breasts, quantitative measures from multiparametric MRI (BPE:breast, FGT:breast, and BPE:vessel ratios) moderately discriminated high- and low-risk groups, warranting further investigation of their value to supplement conventional breast cancer risk assessment tools. Full article
(This article belongs to the Special Issue The Development and Application of Imaging Biomarkers in Cancer)
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23 pages, 4371 KB  
Article
Molecular Characterization and Functional Effect on Canine Peripheral Blood Mononuclear Cells of an Uncharacterized Major Egg Antigen EGR-01664 from Echinococcus granulosus
by Juncheng Huang, Xinwen Bo, Xuke Chen, Jiaxin Zhao, Jianan Zhao, Linying Wei, Yanyan Zhang, Yan Sun and Zhengrong Wang
Genes 2025, 16(11), 1384; https://doi.org/10.3390/genes16111384 - 14 Nov 2025
Viewed by 516
Abstract
Background: Cystic echinococcosis (CE) is a globally distributed zoonosis triggered by the larval stage of Echinococcus granulosus (E. granulosus), impacting humans and an extensive array of mammalian intermediate hosts. EGR-01664 is the major egg antigen of E. granulosus, but almost [...] Read more.
Background: Cystic echinococcosis (CE) is a globally distributed zoonosis triggered by the larval stage of Echinococcus granulosus (E. granulosus), impacting humans and an extensive array of mammalian intermediate hosts. EGR-01664 is the major egg antigen of E. granulosus, but almost nothing is currently known about the function of EGR-01664 from E. granulosus. Methods: This study aimed to investigate the E. granulosus EGR-01664 gene (GenBank ID: 36337379), and the recombinant EGR-01664 protein was expressed successfully. Next, the transcription of the EGR-01664 gene across various developmental stages of E. granulosus was analyzed. Its spatial expression patterns in adult worms and protoscoleces were characterized using both quantitative PCR (qPCR) and immunofluorescence assays. Furthermore, the immunomodulatory effects of rEGR-01664 on cell proliferation, nitric oxide production, and cytokine secretion were examined by co-culturing the recombinant protein with canine PBMCs. Results: The rEGR-01664 could be recognized by sera from dogs infected with E. granulosus. Immunofluorescence assay (IFA) localization revealed the protein’s presence in the epidermis of protoscoleces, the adult epidermis, and some parenchymal tissues. qPCR revealed that EGR-01664 mRNA levels were significantly higher in protoscoleces compared to adults (p < 0.0001). At a concentration of 20 μg/mL, rEGR-01664 could significantly activate the transcription and expression of IL-10, TGF-β1, IL-17A, and Bax in canine PBMCs. However, with an increase in concentration, it inhibited the expression of IFN-γ, Bcl-2, GSDMD, IL-18, and IL-1β. These results suggest that the EGR-01664 gene plays a crucial role in the development, parasitism, and reproduction of E. granulosus. In vitro studies have shown that rEGR-01664 protein regulates the immune regulation function of canine PBMCs, suggesting its potential as a vaccine adjuvant or immunotherapy target. Conclusions: EGR-01664 may modulate canine PBMC functions to regulate host immune responses, thereby facilitating our understanding of how E. granulosus EGR-01664 contributes to the mechanism of parasitic immune evasion. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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7 pages, 9358 KB  
Case Report
Chest Wound Gunshot Management Aided by Cardiopulmonary Bypass: Interdisciplinary Teamwork or “Serendipity”?
by Valentina Tassi, Roland Peraj, Roberto Cirocchi, Valentino Borghetti and Mark Ragusa
Reports 2025, 8(4), 236; https://doi.org/10.3390/reports8040236 - 13 Nov 2025
Viewed by 436
Abstract
Background and clinical significance. Penetrating cardiothoracic wounds require prompt treatment in order to decrease mortality and morbidity. Surgical therapy, aimed at bleeding control and removal of damaged tissue, varies widely from the direct suture of parenchymal lacerations to pneumonectomy, which is characterized by [...] Read more.
Background and clinical significance. Penetrating cardiothoracic wounds require prompt treatment in order to decrease mortality and morbidity. Surgical therapy, aimed at bleeding control and removal of damaged tissue, varies widely from the direct suture of parenchymal lacerations to pneumonectomy, which is characterized by high mortality rates. We report our experience with a patient in hemorrhagic shock due to a gunshot wound to the chest, successfully treated by pneumorrhaphy under cardiopulmonary bypass (CPB). Case presentation. A 53-year-old man with a gunshot wound to the chest was admitted to our Emergency Department. A bedside ultrasonography revealed left pleural and pericardial effusion. He was hemodynamically instable, so he was immediately transferred to the operating room by the cardiac and Thoracic Surgery teams. Through a median sternotomy approximately 2 L of blood were evacuated and a deep laceration of the left upper lobe was discovered. The massive bleeding could not be controlled, leading to pleural cavity flooding. The surgical team decided to institute emergency CPB and perform lung repair by pneumorrhaphy, under circulatory support. The patient survived and was discharged on p.o. day 20. Conclusions. Clinical expertise, adequate instrumental equipment and a high level of interdisciplinary team-work favorably affected the patient’s outcome. Full article
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16 pages, 5122 KB  
Article
Non-Contrast Radiation-Free NIR Lung Imaging
by Jiří Votruba, Martin Drahanský, Tomáš Goldmann, Tomáš Brůha and Radim Kolář
Biomedicines 2025, 13(11), 2757; https://doi.org/10.3390/biomedicines13112757 - 11 Nov 2025
Viewed by 539
Abstract
Background/Objectives: Early localization of solitary pulmonary nodules (SPNs) remains challenging despite technological advances in endoscopic navigation, as the procedure often necessitates multiple ionizing imaging examinations. This study aimed to develop and evaluate a radiation-free optical method for SPN localization based on near-infrared [...] Read more.
Background/Objectives: Early localization of solitary pulmonary nodules (SPNs) remains challenging despite technological advances in endoscopic navigation, as the procedure often necessitates multiple ionizing imaging examinations. This study aimed to develop and evaluate a radiation-free optical method for SPN localization based on near-infrared (NIR) translumination. Methods: A miniaturized NIR light source was introduced into the bronchial tree to illuminate the lung parenchyma. The transmitted and scattered NIR light was detected in real time from the pleural side using minipleuroscopy and a CMOS camera. The approach exploits intrinsic differences in optical absorption and scattering between normal and pathological lung tissue, allowing visualization of the parenchymal micro-architecture without exogenous contrast agents. Results: In ex vivo porcine lungs, tissue structures were clearly visualized through up to approximately 4 cm of parenchyma. In a ventilated pig (n = 1), bronchial NIR illumination was consistently detected from the pleural cavity and produced distinct images of lobular structures and the bronchial mucosa. Conclusions: These feasibility findings demonstrate that NIR translumination can provide radiation-free intra-thoracic visualization and may serve as a valuable adjunct for biopsy guidance. Further quantitative validation and clinical translation are warranted to establish its applicability in human pulmonary procedures. Full article
(This article belongs to the Special Issue Imaging Technology for Human Diseases)
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38 pages, 36156 KB  
Review
Spontaneous Pneumothorax: A Review of Underlying Etiologies and Diagnostic Imaging Modalities
by Rupali Jain, Vinay Kandula, Drew A. Torigian and Achala Donuru
Tomography 2025, 11(11), 125; https://doi.org/10.3390/tomography11110125 - 7 Nov 2025
Viewed by 2627
Abstract
This review focuses on the diverse etiologies of secondary spontaneous pneumothorax (SSP) and the crucial role of imaging in their diagnosis. Unlike primary spontaneous pneumothorax (PSP), which is typically due to ruptured blebs, SSP results from a wide array of underlying pulmonary conditions [...] Read more.
This review focuses on the diverse etiologies of secondary spontaneous pneumothorax (SSP) and the crucial role of imaging in their diagnosis. Unlike primary spontaneous pneumothorax (PSP), which is typically due to ruptured blebs, SSP results from a wide array of underlying pulmonary conditions that can pose significant diagnostic challenges. These include infections like tuberculosis, airway diseases such as chronic obstructive pulmonary disease, malignancies (primary and metastatic), interstitial lung diseases like sarcoidosis, cystic lung diseases such as lymphangioleiomyomatosis, and connective tissue disorders. In women, catamenial pneumothorax secondary to endometriosis should be considered. The role of radiologists is crucial in uncovering these underlying conditions. While chest radiography is the initial imaging modality, computed tomography (CT) provides superior sensitivity for detecting subtle parenchymal abnormalities. Advanced techniques like photon-counting detector CT offer further benefits, including enhanced spatial resolution, reduced noise, and lower radiation dose, potentially revealing underlying causes that might be missed with conventional CT. This enhanced visualization of subtle parenchymal changes, small airways, and vascular structures can be the key to diagnosing the underlying cause of pneumothorax. Recognizing the diverse etiologies of SSP and utilizing advanced imaging techniques is paramount for accurate diagnosis, appropriate management, and improved patient outcomes. Full article
(This article belongs to the Section Cardiovascular Imaging)
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16 pages, 56922 KB  
Article
Translational Evaluation of an Intraparenchymal Collagen Matrix Tamponade: Initial Preclinical and Clinical Experiments to Prevent CSF Reflux Following Endoscopic Brain Surgery
by Yasuo Aihara, Kentaro Chiba, Yuichi Oda, Kevin Browne, Dmitriy Petrov, Takakazu Kawamata and John C. O’Donnell
Int. J. Mol. Sci. 2025, 26(18), 9081; https://doi.org/10.3390/ijms26189081 - 18 Sep 2025
Viewed by 1016
Abstract
Transparent polymer sheaths are often utilized in neuroendoscopic procedures to minimize intraventricular bleeding and parenchymal injuries. However, cerebrospinal fluid (CSF) leakage remains a common complication following neuroendoscopic surgery for intraventricular and deep-seated lesions. We investigated an innovative technique to prevent postoperative CSF leakage [...] Read more.
Transparent polymer sheaths are often utilized in neuroendoscopic procedures to minimize intraventricular bleeding and parenchymal injuries. However, cerebrospinal fluid (CSF) leakage remains a common complication following neuroendoscopic surgery for intraventricular and deep-seated lesions. We investigated an innovative technique to prevent postoperative CSF leakage through the tract using a collagen matrix dural graft. A rolled collagen matrix (DuraGen®) was used as a parenchymal tract tamponade to seal the tract created by an angiocatheter (preclinical pilot) or neuroendoscopic sheath (clinical case studies). A small pilot study using a juvenile pig model was first conducted to test the implantation technique and to evaluate the inflammatory response to, and absorption of intraparenchymal DuraGen. The efficacy of this approach was then assessed in two clinical cases using MRI at postoperative days 1, 7, 40, and 60. The outer segment of the graft was unfurled to cover the dural defect for clinical application. In the pig model, histological analysis showed healing with minimal inflammation in DuraGen®-implanted hemispheres, while untreated control tracts exhibited parenchymal scarring and chronic inflammation. In both patients, postoperative MRI demonstrated resolution of subdural fluid collections and progressive absorption of DuraGen® with no complications. This technique ameliorated CSF leakage and enhanced parenchymal healing after neuroendoscopic surgery. DuraGen® may modulate the local environment for tissue repair beyond its use in dural grafting. Full article
(This article belongs to the Special Issue Regenerative Medicine: Biomaterials and Stem Cell Research)
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41 pages, 9317 KB  
Systematic Review
High-Resolution CT Findings in Interstitial Lung Disease Associated with Connective Tissue Diseases: Differentiating Patterns for Clinical Practice—A Systematic Review with Meta-Analysis
by Janet Camelia Drimus, Robert Cristian Duma, Daniel Trăilă, Corina Delia Mogoșan, Diana Luminița Manolescu and Ovidiu Fira-Mladinescu
J. Clin. Med. 2025, 14(17), 6164; https://doi.org/10.3390/jcm14176164 - 31 Aug 2025
Cited by 1 | Viewed by 6313
Abstract
Objectives: Connective tissue diseases (CTDs) include a diverse group of systemic autoimmune conditions, among which interstitial lung disease (ILD) is acknowledged as a major determinant of prognosis. High-resolution computed tomography (HRCT) is the gold standard for ILD assessment. The distribution of HRCT [...] Read more.
Objectives: Connective tissue diseases (CTDs) include a diverse group of systemic autoimmune conditions, among which interstitial lung disease (ILD) is acknowledged as a major determinant of prognosis. High-resolution computed tomography (HRCT) is the gold standard for ILD assessment. The distribution of HRCT patterns across CTDs remain incompletely defined. The objective of this systematic review is to synthesize available evidence regarding the prevalence of specific radiological patterns within CTD-ILDs and to assess whether specific patterns occur at different frequencies among individual CTDs. Methods: The inclusion criteria encompassed original human studies published in English between 2015 and 2024, involving adult participants (≥18 years) with CTD-ILDs assessed primarily by HRCT and designed as retrospective, prospective, or cross-sectional trials with extractable data. We systematically searched PubMed, Scopus, and Web of Science (January 2025). Risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS) for cohort and case–control studies, and the JBI Critical Appraisal Checklist for cross-sectional studies. Data were extracted and categorized by HRCT pattern for each CTD, and then summarized descriptively and statistically. Results: We analyzed 23 studies published between 2015 and 2024, which included 2020 patients with CTD-ILDs. The analysis revealed non-specific interstitial pneumonia (NSIP) as the most prevalent pattern overall (36.5%), followed by definite usual interstitial pneumonia (UIP) (24.8%), organizing pneumonia (OP) (9.8%) and lymphoid interstitial pneumonia (LIP) (1.25%). HRCT distribution varied by CTD: NSIP predominated in systemic sclerosis, idiopathic inflammatory myopathies, and mixed connective tissue disease; UIP was most frequent in rheumatoid arthritis; LIP was more common in Sjögren’s syndrome. While global differences were statistically significant, pairwise comparisons often lacked significance, likely due to sample size constraints. Discussion: Limitations include varying risk of bias across study designs, heterogeneity in HRCT reporting, small sample sizes, and inconsistent follow-up, which may reduce precision and generalizability. In addition to the quantitative synthesis, this review offers a detailed description of each radiologic pattern mentioned above, illustrated by representative examples to support the recognition in clinical settings. Furthermore, it includes a brief overview of the major CTDs associated with ILD, summarizing their epidemiological data, risk factors for ILD and clinical presentation and diagnostic recommendations. Conclusions: NSIP emerged as the most common HRCT pattern across CTD-ILDs, with UIP predominating in RA. Although inter-disease differences were observed, statistical significance was limited, likely reflecting sample size constraints. These findings emphasize the diagnostic and prognostic relevance of HRCT pattern recognition and highlight the need for larger, standardized studies. Full article
(This article belongs to the Special Issue Advances in Pulmonary Disease Management and Innovation in Treatment)
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14 pages, 1906 KB  
Article
AI-Based HRCT Quantification in Connective Tissue Disease-Associated Interstitial Lung Disease
by Anna Russo, Vittorio Patanè, Alessandra Oliva, Vittorio Viglione, Linda Franzese, Giulio Forte, Vasiliki Liakouli, Fabio Perrotta and Alfonso Reginelli
Diagnostics 2025, 15(17), 2179; https://doi.org/10.3390/diagnostics15172179 - 28 Aug 2025
Cited by 1 | Viewed by 1495
Abstract
Background: Interstitial lung disease (ILD) is a frequent and potentially progressive manifestation in patients with connective tissue diseases (CTDs). Accurate and reproducible quantification of parenchymal abnormalities on high-resolution computed tomography (HRCT) is essential for evaluating treatment response and monitoring disease progression, particularly in [...] Read more.
Background: Interstitial lung disease (ILD) is a frequent and potentially progressive manifestation in patients with connective tissue diseases (CTDs). Accurate and reproducible quantification of parenchymal abnormalities on high-resolution computed tomography (HRCT) is essential for evaluating treatment response and monitoring disease progression, particularly in complex cases undergoing antifibrotic therapy. Artificial intelligence (AI)-based tools may improve consistency in visual assessment and assist less experienced radiologists in longitudinal follow-up. Methods: In this retrospective study, 48 patients with CTD-related ILD receiving antifibrotic treatment were included. Each patient underwent four HRCT scans, which were evaluated independently by two radiologists (one expert, one non-expert) using a semi-quantitative scoring system. Percentage estimates of lung involvement were assigned for four parenchymal patterns: hyperlucency, ground-glass opacity (GGO), reticulation, and honeycombing. AI-based analysis was performed using the Imbio Lung Texture Analysis platform, which generated continuous volumetric percentages for each pattern. Concordance between AI and human interpretation was assessed, along with mean absolute error (MAE) and inter-reader differences. Results: The AI-based system demonstrated high concordance with the expert radiologist, with an overall agreement of 81% across patterns. The MAE between AI and the expert ranged from 1.8% to 2.6%. In contrast, concordance between AI and the non-expert radiologist was significantly lower (60–70%), with higher MAE values (3.9% to 5.2%). McNemar’s and Wilcoxon tests confirmed that AI aligned more closely with the expert than the non-expert reader (p < 0.01). AI proved particularly effective in detecting subtle changes in parenchymal burden during follow-up, especially when visual interpretation was inconsistent. Conclusions: AI-driven quantitative imaging offers performance comparable to expert radiologists in assessing ILD patterns on HRCT and significantly outperforms less experienced readers. Its reproducibility and sensitivity to change support its role in standardizing follow-up evaluations and enhancing multidisciplinary decision-making in patients with CTD-related ILD, particularly in progressive fibrosing cases receiving antifibrotic therapy. Full article
(This article belongs to the Special Issue Application of Radiomics in Clinical Diagnosis)
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12 pages, 456 KB  
Article
From Variability to Standardization: The Impact of Breast Density on Background Parenchymal Enhancement in Contrast-Enhanced Mammography and the Need for a Structured Reporting System
by Graziella Di Grezia, Antonio Nazzaro, Luigi Schiavone, Cisternino Elisa, Alessandro Galiano, Gatta Gianluca, Cuccurullo Vincenzo and Mariano Scaglione
Cancers 2025, 17(15), 2523; https://doi.org/10.3390/cancers17152523 - 30 Jul 2025
Cited by 2 | Viewed by 2220
Abstract
Introduction: Breast density is a well-recognized factor in breast cancer risk assessment, with higher density linked to increased malignancy risk and reduced sensitivity of conventional mammography. Background parenchymal enhancement (BPE), observed in contrast-enhanced imaging, reflects physiological contrast uptake in non-pathologic breast tissue. [...] Read more.
Introduction: Breast density is a well-recognized factor in breast cancer risk assessment, with higher density linked to increased malignancy risk and reduced sensitivity of conventional mammography. Background parenchymal enhancement (BPE), observed in contrast-enhanced imaging, reflects physiological contrast uptake in non-pathologic breast tissue. While extensively characterized in breast MRI, the role of BPE in contrast-enhanced mammography (CEM) remains uncertain due to inconsistent findings regarding its correlation with breast density and cancer risk. Unlike breast density—standardized through the ACR BI-RADS lexicon—BPE lacks a uniform classification system in CEM, leading to variability in clinical interpretation and research outcomes. To address this gap, we introduce the BPE-CEM Standard Scale (BCSS), a structured four-tiered classification system specifically tailored to the two-dimensional characteristics of CEM, aiming to improve consistency and diagnostic alignment in BPE evaluation. Materials and Methods: In this retrospective single-center study, 213 patients who underwent mammography (MG), ultrasound (US), and contrast-enhanced mammography (CEM) between May 2022 and June 2023 at the “A. Perrino” Hospital in Brindisi were included. Breast density was classified according to ACR BI-RADS (categories A–D). BPE was categorized into four levels: Minimal (< 10% enhancement), Light (10–25%), Moderate (25–50%), and Marked (> 50%). Three radiologists independently assessed BPE in a subset of 50 randomly selected cases to evaluate inter-observer agreement using Cohen’s kappa. Correlations between BPE, breast density, and age were examined through regression analysis. Results: BPE was Minimal in 57% of patients, Light in 31%, Moderate in 10%, and Marked in 2%. A significant positive association was found between higher breast density (BI-RADS C–D) and increased BPE (p < 0.05), whereas lower-density breasts (A–B) were predominantly associated with minimal or light BPE. Regression analysis confirmed a modest but statistically significant association between breast density and BPE (R2 = 0.144), while age showed no significant effect. Inter-observer agreement for BPE categorization using the BCSS was excellent (κ = 0.85; 95% CI: 0.78–0.92), supporting its reproducibility. Conclusions: Our findings indicate that breast density is a key determinant of BPE in CEM. The proposed BCSS offers a reproducible, four-level framework for standardized BPE assessment tailored to the imaging characteristics of CEM. By reducing variability in interpretation, the BCSS has the potential to improve diagnostic consistency and facilitate integration of BPE into personalized breast cancer risk models. Further prospective multicenter studies are needed to validate this classification and assess its clinical impact. Full article
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9 pages, 8072 KB  
Article
C4d Immunoreactivity in Autoimmune and HBV-Induced Hepatitis: Implications for Complement-Mediated Hepatocellular Injury
by Ye Zheng, Haitao Tong, Wenjuan Guo, Ao Wang, Wenxing Hu, Min Wu and Xiaonan Zhang
Pathophysiology 2025, 32(3), 30; https://doi.org/10.3390/pathophysiology32030030 - 1 Jul 2025
Viewed by 870
Abstract
Background: Although immune complex formation is widely acknowledged as the etiological agent for the development of systemic lupus erythematosus, polyarteritis nodosa, reactive arthritis, etc., its roles in chronic hepatitis are less understood. This study aims to compare the immunohistochemistry profile of immune complex [...] Read more.
Background: Although immune complex formation is widely acknowledged as the etiological agent for the development of systemic lupus erythematosus, polyarteritis nodosa, reactive arthritis, etc., its roles in chronic hepatitis are less understood. This study aims to compare the immunohistochemistry profile of immune complex deposition in patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH). Methods: Immunohistochemistry of C4d, a widely used marker for complement deposition was employed on liver biopsies from 72 and 15 patients with CHB and AIH, respectively. Statistical analysis was performed to analyze its prevalence and its association with a range of clinical and histological parameters. Results: Among the 15 AIH biopsies examined, C4d deposition was observed in 11 cases (73.3%), the majority of which showed a periportal staining pattern (10/11). In CHB, 61 (84.7%) of 72 cases tested positive for C4d, which did not differ significantly with that of AIH. While the periportal pattern was predominantly observed in CHB cases, positive staining in central veins, sinusoids, and hepatic parenchyma were also documented. In particular, C4d deposition is significantly associated with elevated serum ALT and liver inflammation in CHB. Of note, in specimens with a patchy parenchymal C4d staining pattern, a spatially correlated HBsAg IHC signal was observed in adjacent sections from the same tissue. Conclusions: These data suggest an involvement of immune complex-mediated immunopathy in autoimmune hepatitis and HBV-induced hepatitis. The positive intrahepatic C4d signal was associated with heightened liver inflammation. The colocalization of the C4d signal on hepatocytes with HBsAg strongly suggests a causal relationship between viral activity and complement deposition. These observations align with our recent evidence implicating the contribution of capsid–antibody complexes in the pathogenesis of CHB. Full article
(This article belongs to the Section Systemic Pathophysiology)
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7 pages, 1272 KB  
Case Report
Extraovarian Brenner Tumor in the Vagina: A Case Report and Review of Literature
by Angel Yordanov, Milen Karaivanov, Stoyan Kostov, Vanya Savova and Vasilena Dimitrova
Reports 2025, 8(3), 103; https://doi.org/10.3390/reports8030103 - 29 Jun 2025
Cited by 1 | Viewed by 1372
Abstract
Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in [...] Read more.
Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in the ovary, extraovarian Brenner tumors (EOBTs) have been reported in the uterus, vagina, broad ligament, and omentum. Case Presentation: A 71-year-old postmenopausal woman presented with a polypous formation on the upper third of the posterior vaginal wall, which was found at a routine health check. Macroscopically, the lesion appeared as a solid, polypoid mass with a yellowish-gray cut surface, measuring approximately 25 × 20 mm. Histological examination revealed a polypoid formation covered by stratified squamous epithelium, with a dense fibrous stroma (Van Gieson [VG]+) and tubular structures lined by clear epithelial cells. Parenchymal cells showed low proliferative activity, with Ki-67 expression in less than 5% of cells, also Cytokeratin (CK) 7/+/p63:/+/ CK AE1/AE3: /+/ Estrogen Receptor (ER): /+/ and Progesterone Receptor (PR)/−/; CK20/-/; p53/−/, Wilms’ Tumor (WT)-1/−/; Prostate-Specific Acid Phosphatase (PSAP)/−/. The final diagnosis was an extraovarian Brenner tumor. The patient was monitored for two months post-excision, with no signs of recurrence. Conclusions: EOBTs are extremely rarely seen and vaginal involvement is far less common. Due to their rarity, these tumors may be confused with other benign or malignant vaginal lesions. In order to differentiate EOBTs from other neoplasms, histological analysis is crucial due to their characteristic transitional-type epithelium and large fibrous stroma. Further studies are required to understand the origin and clinical behavior of EOBTs. Long-term monitoring should be performed to look for any recurrence or malignant change, even though benign Brenner tumors usually have a good prognosis. Awareness of EOBTs and their possible locations is essential for accurate diagnosis and appropriate management. Full article
(This article belongs to the Section Obstetrics/Gynaecology)
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