Search Results (311)

Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in the human liver which can provide antimicrobial defense, amplify inflammatory processes and mediate tissue repair and fibrosis depending on microenvironmental cues. Chronic liver diseases of diverse etiologies, including viral hepatitis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, biliary tract disease, autoimmune hepatitis and hepatocellular carcinoma are accompanied by numerical and functional adjustments in the MAIT cell population. In this review, we integrate existing data on MAIT cell markers and functions in diverse liver diseases, comparing how these cells are similarly or differentially shaped by distinct pathogenic contexts. Finally, we propose a spatially anchored conceptual and technical framework to study MAIT cell biology in liver disease. Full article

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal neurological disorder caused by persistent measles virus infection. Reliable prognostic biomarkers remain limited. Systemic inflammation has been implicated in the pathogenesis of neuroinfectious diseases, and hematology-derived indices are increasingly recognized as accessible markers of inflammatory burden. This retrospective case–control study was conducted at İnönü University Faculty of Medicine, Malatya, Türkiye, between 2010 and 2025, including 40 pediatric patients with SSPE and 40 age- and sex-matched healthy controls. Demographic and laboratory data were retrieved from institutional records, and disease severity was classified according to Jabbour stages. Compared with controls, patients with SSPE had significantly higher pan-immune inflammation value (PIV: 710.5 [320–1050] vs. 280.0 [150–460], p < 0.001), systemic immune-inflammation index (SII: 640.0 [310–1240] vs. 410.0 [210–720], p = 0.02), and neutrophil-to-lymphocyte ratio (NLR: 2.1 [1.2–3.8] vs. 1.6 [1.0–2.5], p = 0.03), along with lower lymphocyte counts (p = 0.04). Elevated PIVs were strongly associated with advanced Jabbour stages, impaired ambulation, and a higher case-fatality ratio (35%). Multivariate regression identified PIV as an independent predictor of death (OR: 3.25, 95% CI: 1.45–7.28, p = 0.004), and receiver operating characteristic analysis demonstrated superior discriminative accuracy of PIV (AUC = 0.87) compared with other indices. These findings suggest that PIV, a simple and inexpensive biomarker derived from routine blood tests, may provide useful prognostic information in SSPE and aid early risk stratification. Further multicenter, prospective studies are warranted to validate its clinical utility. Full article

Cholangiopathies encompass a wide range of chronic liver diseases that target biliary epithelial cells, leading to significant morbidity and mortality due to their progressive nature, limited treatment options, and complex clinical management. Currently, clinically validated biomarkers capable of distinguishing obstructive cholangiopathies, such as biliary atresia (BA), from other cholangiopathies are lacking, hindering timely intervention. RNA-binding proteins (RBPs) have been increasingly linked to human diseases but their roles in cholangiopathies remain underexplored. We assessed the expression of the RBP epithelial splicing regulatory protein 1 (ESRP1) in murine models of cholangiopathies and in the human system. Our findings demonstrate that ESRP1 is highly and specifically expressed in cholestatic liver injury models, including bile duct-ligated, diethoxycarboncyl-1,4-dihydrocollidine-treated, and Mdr2^−/− mice when compared with other liver injury models. Importantly, ESRP1 is markedly elevated in the livers of patients with BA and cystic fibrosis-related liver disease, localizing to cholangiocytes and peri-biliary hepatic cells, but is minimal in primary sclerosing cholangitis and primary biliary cholangitis. Moreover, patient-derived BA organoids and biliatresone-treated healthy organoids also display ESRP1 expression. Bioinformatics analysis further implicates ESRP1 in key cholangiopathy-associated pathways, warranting deeper mechanistic investigation. Thus, ESRP1 holds potential as a molecular marker for obstructive cholangiopathies, warranting further mechanistic studies. Full article

In the lateral neck area (LNA), the parotid glands and submandibular glands can be diagnosed with various lesions, especially cysts and tumors of different etiology. In the submandibular area, many lesions are related to salivary stones and some inflammations, causing a secondary gland enlargement. When no sialolithiasis is present, a close relation to other local inflammation causes, IgG4, or related chronic sclerosing disease should be estimated. Ultrasound evaluation seems to be sufficient to indicate any occurrence of salivary retention, inflammation, dilatation of ducts, and gland swelling, and to confirm the initial diagnosis of sialolithiasis or sialadenitis. Any possible tumor formation or tumor-like solid mass evaluation requires adequate computed tomography or magnetic resonance imaging. A very important question should be raised if clinical symptoms like neck asymmetry, submandibular swelling, and solid-mass formation always correspond with radiological as well as some worrisome oncological symptoms. On the other hand, when radiological imaging is insufficient or lacking, a fine needle biopsy would be useful. Problems arise when any signs of potential disease or other tumor-like lesions are inconclusive or indicate inflammation, and possible treatment options are limited. Secondly, when patient anamnesis and blood examination are normal, but a worrisome tumor-like appearance progresses in time, a serious question about improved diagnostics and scheduling for surgery should be raised. Not all cases of elevated serum IgG4 levels correspond with IgG4 lesions and the typical spectrum of those diseases, and therefore histopathological examination of excised lesion provides the scope of the following disease intensity. In the following interesting images, it is worth noticing that radiological, clinical, needle biopsy, and cytological examinations do not always correlate with each other, and in some cases, an open surgery should be considered to improve the diagnosis. Full article

Background: Primary Sclerosing Cholangitis (PSC), Primary Biliary Cholangitis (PBC), and Autoimmune Hepatitis (AIH) are rare immune-mediated liver conditions that significantly affect patients’ quality of life. In Romania, access to specialized information and patient support resources is limited, underscoring the need for tailored educational tools. The aim was to describe the methodology for developing, implementing, and conducting a feasibility study of an online platform for patients with PSC, PBC, and AIH, as a pilot study, providing early insights. Methods: The platform offers educational materials, registration, a discussion forum, and digital tools for quality-of-life assessment. Data on demographics, usage, and quality of life were collected using standardized questionnaires (CLDQ-PSC, PBC-10) and non-standardized questionnaires, and analyzed with Microsoft Office Excel and DATATab. Results: The website was created using an online platform requiring no advanced IT skills. Content was developed in accordance with international guidelines (EASL, AASLD) and translated and adapted for Romanian patients. As of 15 July 2025, 81 patients had been registered (26% PSC, 68% PBC, 6% AIH), with a predominance of urban participants (all patients: 87% female, mean age at diagnosis = 44.5 years). Most participants used mobile devices and reported improved understanding and engagement with their health after using the platform. Conclusions: The first dedicated digital platform has been established in Romania to address the health literacy needs of patients with PSC, PBC, and AIH. The study offers insights into future directions and a replicable model for similar initiatives. The pilot evaluation of the platform faced several limitations, including self-selection bias, non-standardized assessments, and a small sample size. Full article

Background/Objectives: Biliary reconstruction in liver transplantation (LT) for primary sclerosing cholangitis (PSC) is controversial. A Roux-en-Y hepaticojejunostomy (HJ) is associated with fewer anastomotic strictures, while a duct-to-duct reconstruction (DD) shows a decreased rate of cholangitis and preserves anatomy for endoscopy. The aim of our study was to analyze patient survival and postoperative outcomes after LT for PSC based on the type of reconstruction in two high-volume LT centers. Methods: We included 94 PSC patients who underwent a primary LT between 2010 and 2024. The association of biliary reconstruction with patient survival was assessed with the Kaplan–Meier method. Predictors of mortality and postoperative complications were identified via Cox and logistic regression. Results: In total, 42 patients received an HJ and 52 patients received a DD. There was no difference in patient survival or major complications. DD resulted in an increased number of anastomotic strictures, whereas anastomotic insufficiency, ischemia, cholangitis, and the need for revision surgery showed no difference. The choice of biliary reconstruction technique was not a predictor for mortality or major complications. Conclusions: Both types of biliary reconstruction are effective for PSC patients, with comparable patient survival and postoperative outcomes. Although DD is associated with an increased number of strictures, endoscopic treatment options provide a feasible solution. Full article

Background: The treatment of soft tissue vascular anomalies is a challenge in materials science, requiring injectable biomaterials that can conform to complex lesion architectures while providing controlled drug delivery. Conventional liquid sclerosants fail due to poor localization. This study reports on the formulation and clinical performance of an in situ-forming, drug-eluting composite foam designed to overcome these limitations. Methods: A multicomponent composite foam was formulated from a liquid phase containing bleomycin and polidocanol and a gaseous phase of room air using a standardized Tessari emulsification technique. The therapeutic performance of this composite was evaluated retrospectively in 14 patients with high-risk airway venous malformations (AVMs) by quantifying lesion volume reduction on magnetic resonance imaging (MRI) and assessing clinical outcomes. Biocompatibility was determined by monitoring adverse tissue reactions. Results: The injectable composite foam demonstrated superior clinical performance with a 100% therapeutic response rate. Full target lesion ablation, defined as a complete response, was achieved in 10 of 14 cases (71.4%), demonstrating the composite’s high efficacy. The material exhibited excellent biocompatibility, with adverse events limited to minor, localized mucosal necrosis (21.4%) that resolved without intervention, indicating predictable material-tissue interaction. Conclusions: The bleomycin-polidocanol composite foam is an effective, therapeutic biomaterial whose performance is directly linked to its unique physicochemical structure. This work validates a material-based strategy for treating complex vascular lesions and highlights the potential for further optimization of such injectable composites by enhancing their long-term stability. Full article

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease in the United States and frequently coexists with other liver diseases. Despite growing interest, the presence of MASLD in patients with primary sclerosing cholangitis (PSC) remains underexplored. This study aimed to assess the prevalence and characteristics of the MASLD-PSC overlap syndrome, with a specific focus on patient-reported outcomes such as pruritus and fatigue. Methods: A cross-sectional analysis was performed within a prospective cohort of patients with PSC enrolled in the Autoimmune Liver Diseases Registry at a United States tertiary medical center (2018–2024). MASLD overlap was established based on evidence of hepatic steatosis on liver imaging or biopsy, combined with at least one cardiometabolic risk factor. Fatigue and pruritus were assessed using the Chronic Liver Disease Questionnaire (CLDQ) and the 5D Itch Scale. Ordinal logistic regression models were used to explore the potential impact of MASLD overlap on fatigue and pruritus severity. Results: Among 103 PSC patients, 33% had MASLD overlap. These patients were older (55 vs. 46 years, p = 0.006), had a higher BMI (30 vs. 25 kg/m², p < 0.001), and were more likely to have small bile duct involvement (43% vs. 12%, p = 0.002). A history of liver transplantation (LT) was noted in 18% of PSC-only patients, compared to 3% of those with PSC/MASLD (p = 0.055). MASLD overlap was significantly associated with higher pruritus intensity (OR 3.09, 95% CI 1.02–9.28, p = 0.044), but was paradoxically linked to lower fatigue levels (OR 0.37, 95% CI 0.16–0.85, p = 0.020). Conclusions: Patients with PSC/MASLD exhibit distinct clinical features. MASLD overlap was found to significantly impact patient-reported outcomes, with lower fatigue intensity but increased pruritus severity, suggesting a role for metabolic or inflammatory pathways, warranting further investigation. Full article

Background/Objectives: Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma with high rates of local recurrence and distant metastasis. Primary spinal involvement is exceedingly uncommon and often misdiagnosed due to radiological and histopathological resemblance to more frequent spinal tumors. The objective of this study is to present a rare case of thoracic spinal SEF and to contextualize it within the available literature. Methods: We describe the case of a 37-year-old woman presenting with progressive back pain and dysesthesia. MRI demonstrated a heterogeneously enhancing mass at the left T10–T11 neural foramen, initially interpreted as a common nerve sheath tumor. Gross total resection (GTR) was achieved, and histopathological analysis revealed a SEF. Clinical course, adjuvant therapies, and outcomes were evaluated, together with a review of previously reported spinal SEF cases. Results: Despite GTR followed by adjuvant chemotherapy, local recurrence occurred 18 months later. The patient underwent subtotal resection (STR) with adjuvant proton therapy. At 18-month follow-up after the second procedure, she remained neurologically stable and disease-free. The literature review confirmed the rarity of spinal SEF, its frequent misdiagnosis, and the absence of standardized therapeutic protocols. Conclusions: Spinal SEF is a rare malignancy that can mimic benign spinal tumors, delaying diagnosis. Its management relies on multidisciplinary assessment, individualized therapy, and long-term follow-up. This report increases awareness of spinal SEF and provides additional evidence to support clinical decision-making in rare spinal tumors. Full article

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut–liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut–liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut–liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC. Full article

Objectives: Venous malformations (VMs) that infiltrate the muscular layer, involve or are closely adjacent to critical nerves or vessels, or are located deep within or very close to major organs in the thoracic or abdominal cavities are challenging to access during sclerotherapy, which we defined as inaccessible VMs. This study proposed an integrated real-time stereotactic MRI-guided sclerotherapy with bleomycin-polidocanol foam (RSMS-BPF) for the treatment of inaccessible VMs, focusing on its clinical feasibility, efficacy, and safety. Methods: A retrospective study was conducted involving patients treated with RSMS-BPF between 2019 and 2021. During the sclerotherapy, the intraoperative magnetic resonance imaging (MRI) was combined with an optical navigation system to guide precise needle placement and track BPF, a foam sclerosant optimized for MRI visibility. Radiological response was assessed by lesion volume, while clinical improvement was evaluated through patients’ description of their symptoms. Rigorous follow-up and documentation of complications were conducted. Results: A total of 42 patients (mean age 23.6 ± 1.6 years; 18 males) were treated in 64 sclerotherapy sessions. The treatment achieved an overall response rate of 89.5%. Imaging analysis revealed an average lesion volume reduction of 59.6%. 57.9% of patients achieved good or excellent radiological responses. After a median follow-up of 12.25 months, 60.53% of patients reported complete or significant relief. Lesion depth did not affect treatment efficacy (p = 0.43). Minor complications included skin hyperpigmentation (5.3%, 2/38) and blisters (2.6%, 1/38), with no major complications observed. Conclusions: RSMS-BPF demonstrated satisfactory efficacy and safety in VMs treatment, particularly for inaccessible VM lesions. It enables authentic real-time dynamic tracking during sclerotherapy, achieving unparalleled precision targeting while minimizing procedural risks. These findings strongly support routine integration of RSMS-BPF as first-line therapy for complex vascular malformations with critical anatomical constraints. Full article

Background: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease characterised by bile duct strictures. Magnetic resonance cholangiopancreatography (MRCP) is the principal imaging modality for diagnosis; however, its interpretation is subjective. Quantitative MRCP (MRCP+) provides quantitative assessment of the biliary anatomy and can support objective disease assessment. We evaluated the potential impact, feasibility, and perceived usefulness that MRCP+ would have on PSC patient management. Methods: Alongside systematic evaluation of UK and European clinical guidelines on PSC management, semi-structured interviews with 16 stakeholders were conducted. The Lean Assessment Process methodology was used to assess potential impact and feasibility of adopting MRCP+ for the PSC care pathway within the NHS. Price as a barrier to adoption was investigated to evaluate perceptions between technology cost and adoption. Perceived ease of use and perceived trust were calculated and used to evaluate perceived usefulness (PU). Results: For PSC management, MRCP (81%) scored higher than liver biopsy (68%) and ERCP (50%) due to its non-invasive nature. There was good internal consistency between responders on the relationship between price point and the use of MRCP+ to support diagnosis (CA:0.836) and monitoring (CA:0.904). A price point of up to GBP 500 was unlikely to be a barrier for adoption. The overall perceived usefulness for MRCP+ for patient management was 74%. Conclusions: There is strong interest in using MRCP+ to support PSC management. MRCP+ has the potential to address unmet needs including reducing subjectivity, measurement of the whole biliary tree and objectively measuring biliary disease progression. Full article

Background and Objectives: Breast lesions of uncertain malignant potential identified on biopsy, known as “B3 lesions,” constitute a significant portion of diagnoses in numerous published studies. These lesions are associated with a variable risk of coinciding malignant tumors, and current guidelines recommend complete excision, which can occasionally lead to an upgrade in the resection specimen. However, alternative, less invasive treatment strategies, such as clinical follow-up, may be considered. In this study, we retrospectively analyzed diagnostic biopsies from our institution to determine the upgrade rate of each B3 lesion subgroup to breast malignancy following complete excision. Materials and Methods: All breast biopsies conducted at our institution from 1 January 2018 to 30 November 2022 and classified as B3 lesions were included in this study. The lesions were categorized into groups and subgroups based on their growth pattern and histopathological features. To determine the upgrade rate to ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC) for each B3 lesion subgroup, we assessed the histological concordance between the biopsy and the resection specimen. Results: During the study period, 10,531 biopsies were performed, of which 1045 (9.93%) were classified as B3 lesions. Among these, 795 (76.08%) were subsequently resected, either through surgical procedures (98.32%) or using the Vacuum-Assisted Excision technique (1.68%). Histological examination revealed that 89 (11.19%) of the resected B3 lesions were upgraded to breast malignancy, with 59 cases (7.42%) progressing to DCIS, 22 cases (2.76%) to IBC, and 8 cases (1.01%) to borderline or malignant phyllodes tumor. The upgrade rate varied among histopathological subgroups, being lowest in complex sclerosing lesions without atypia (4.95%, 95% CI: 2.5–8.7%) and highest in intraductal papillomas with atypia (58.82%; 95% CI: 32.9–81.6%). Conclusions: Statistically significant differences were observed between B3 lesion subgroups, with a higher risk of upgrade in lesions exhibiting atypia. As our understanding of B3 lesions evolves, there is potential to implement therapeutic strategies tailored to the specific risk associated with each subgroup. This approach could allow for less invasive management options, such as clinical or radiological follow-up, thereby sparing patients from unnecessary invasive procedures when appropriate. Full article

Autoimmune liver diseases (AILDs) represent a diverse spectrum of chronic inflammatory conditions characterized primarily by compromised hepatic immune tolerance, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Recent evidence positions macrophages as pivotal players in AILDs pathogenesis, attributable to their multifaceted roles in inflammation amplification, immune regulation, and fibrogenesis. In the context of AILDs, macrophages exhibit marked polarization imbalance, increased recruitment of monocytes, and impaired clearance of apoptotic cells. Through complex interactions with T lymphocytes and hepatic stellate cells, macrophages orchestrate a pathological milieu promoting inflammation and fibrosis. Notably, diverse programmed cell death (PCD) modalities—autophagy, necroptosis, pyroptosis, and ferroptosis—not only determine macrophage survival and functional phenotype but also significantly impact cytokine release, phenotypic plasticity, and the trajectory of immunopathological progression. This review synthesizes current understandings of macrophage-driven immunoregulatory mechanisms in AILDs, characterizes the regulatory attributes of various macrophage-related PCD processes, and evaluates their relevance in experimental disease models. Furthermore, we highlight recent advancements in biomarker identification and targeted therapeutic strategies. Comprehensive elucidation of the interplay between macrophage immunological activity and programmed cell death pathways promises to inform novel, personalized therapeutic approaches for patients with AILDs. Full article

Malignant pericardial effusion (MPE) is a life-threatening condition in patients with cancer, with common recurrences after simple pericardiocentesis. Consequently, the intrapericardial instillation of sclerosing or cytotoxic agents has been explored, with limited evidence from small studies with different methodologies. We undertook an observational, retrospective, single-centre study, including all patients diagnosed with a solid neoplasm and clinically significant and/or recurrent, cytology-confirmed MPE, treated with Intrapericardial Instillation of Cisplatin (IPIC), between 2009 and 2022. Patients with hematological malignancies were excluded. The procedure followed a multidisciplinary approach and a standardized protocol. Variables collected included baseline patient characteristics, neoplasm details, MPE impact, adverse events (AEs) from procedures (pericardiocentesis and IPIC) and outcomes (time to MPE recurrence and survival). This study adhered to the STROBE guidelines. A total of 41 patients were included, 51% female, with a median age of 61 (51–69) years. Non-small cell lung cancer (NSCLC) was the predominant primary tumour (78%) and in 44% of the cohort, MPE was identified at cancer diagnosis. Most patients (90.2%) presented symptoms related to MPE at diagnosis, and 88% had cardiac tamponade on echocardiography. IPIC was administered a median of four times. IPIC-related AEs occurred in 10 patients (24.4%), with transient atrial fibrillation (AF) being the most frequent one. Two patients (4.9%) experienced MPE recurrence within 30 days after IPIC. The median survival time from MPE diagnosis was 161 days (5.4 months; IQR 73–455 days). IPIC appears to be a feasible, effective and safe option for reducing the risk of MPE recurrence, mainly in NSCLC. Full article