Background: Malnutrition affects patients undergoing surgery for gastrointestinal cancers and contributes to poor postoperative outcomes, including increased complication rates, longer hospital stays, and higher mortality. Despite the availability of several malnutrition screening tools and prognostic scores, their effectiveness in predicting postoperative outcomes remains unclear. This study aimed to compare the predictive accuracy of Patient-Generated Subjective Global Assessment (PG-SGA), Global Leadership Initiative on Malnutrition (GLIM), Geriatric Nutritional Risk Index (GNRI), and Controlling Nutritional Status (CONUT) score for postoperative outcomes in patients undergoing surgery for colorectal, hepato-pancreato-biliary and upper gastrointestinal cancers. Methods: A cross-sectional observational study from March 2022 to October 2023 was conducted in two university surgical departments, after registration on ClinicalTrials database (NCT05795374). Patient characteristics, preoperative nutritional status and postoperative outcomes were analyzed. Results: In total, 480 patients were enrolled. CONUT and GNRI demonstrated high specificity (over 90% and 80%, respectively) for predicting overall complications, major complications, prolonged hospital stay, mortality, and advanced disease stage across all cancer types. Notably, CONUT showed a specificity over 97% and GNRI over 89.7% for colorectal and upper gastrointestinal cancer patients, respectively, despite their lower sensitivity. On the contrary, PG-SGA and GLIM presented better sensitivity (up to 50%), but slightly lower specificity (up to 86.4%). Conclusions: CONUT and GNRI are valuable for ruling out non-at-risk patients for adverse postoperative outcomes, while PG-SGA and GLIM provide better sensitivity. A step-up approach—initial screening with PG-SGA and GLIM, followed by detailed evaluation with CONUT or GNRI— should be validated in future studies across diverse clinical settings.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an integrative and stage-dependent synthesis of current mechanistic insights into how bidirectional crosstalk between CS and LD regulation shapes the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, including upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can activate peroxisome-proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent CS under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid oxidation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor—kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. By framing LDs as active modulators of senescence-associated signaling rather than passive lipid stores, this review highlights how disruption of senescence–lipid feedback loops may represent a disease-modifying opportunity in MASLD progression.

Background: Burn injuries remain a major clinical problem worldwide, which require special management by experienced plastic surgeons. However, they cannot be available in every healthcare unit; consequently, there is a need for effective treatment options that could be utilized by a wide range of non-expert healthcare professionals. The aim of the present experimental study was to investigate the safety and efficacy of using a fibrin sealant (TISSEEL^TM) compared to the conventional treatment with sulfadiazine on partial-thickness burn in a rat animal model. Methods: A cohort of Sprague Dawley rats underwent partial-thickness contact thermal burn wounds and were divided into three study groups: control group (no treatment), silver sulfadiazine cream group and TISSEEL^TM group. Following animal sacrifice, a blinded histopathologic analysis was conducted regarding inflammatory response, healing and tissue regeneration. Results: In total, 30 animals were included with a median weight of 236 ± 10 g. Two animals from the control group died on the first postoperative day. Animals in the TISSEEL^TM group presented dominant collagen expression compared to animals in the control and silver sulfadiazine cream group (p = 0.000). Histopathologic analysis also demonstrated marked leukocyte infiltration (p = 0.009), increased neovascularization (p = 0.000) and higher fibroblast expression (p = 0.002) in the TISSEEL^TM group compared to the other two groups. Conclusions: TISSEEL^TM seems to be a safe alternative (or even principal) option for the initial therapeutic approach of partial-thickness burn injuries. Moreover, it seems to be superior to silver sulfadiazine in terms of tissue healing and regeneration. However, additional experimental as well as clinical research is necessary prior to implementation in clinical practice.

Chemotherapy with cisplatin (CDDP) and etoposide (ETO) is the standard treatment for gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). Despite high initial response rates, treatment-related toxicity and acquired resistance remain significant clinical challenges. No molecularly targeted therapies are currently established for this aggressive cancer. Here, we evaluated Aurora kinase inhibition with alisertib (ALI) as a synthetic lethality strategy in ARID1A-deficient GEP-NEC. Subcutaneous and orthotopic xenograft models were established in immunodeficient mice using the GEP-NEC-derived NT-38 cell line, and the therapeutic efficacy of ALI was compared with CDDP + ETO. Tumor responses were assessed by immunohistochemistry, Western blotting, and RNA sequencing. To confirm ARID1A dependency, transient knockdown was induced in the pancreatic neuroendocrine NT-18LM cell line, demonstrating that ALI sensitivity is significantly enhanced in ARID1A-deficient cells. ALI achieved antitumor efficacy comparable to chemotherapy and was well tolerated, with minimal weight loss relative to CDDP + ETO. Distant metastases, an early feature of GEP-NEC, developed in five animals over six weeks, two of which were treated with ALI and three controls. Transcriptomic profiling revealed convergence of both treatments on signal transduction, focal adhesion, receptor tyrosine kinase, and VEGFA-VEGFR2 signaling, while ALI uniquely enriched pathways related to pancreatic secretion, lipid metabolism, protein processing in the endoplasmic reticulum, and extracellular matrix organization. These findings establish Aurora kinase inhibition as mechanistically distinct and selectively effective in ARID1A-deficient GEP-NEC. Given its efficacy, favorable tolerability, and ARID1A-dependent specificity, ALI may represent a promising alternative to platinum-based chemotherapy, offering a strong rationale for further development of mechanism-driven combination strategies for GEP-NEC.

Background: Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD), yet the clinical significance of tight junction (TJ) remodeling remains unclear. We investigated whether alterations in the expression and localization of key TJ proteins are associated with disease activity and clinical outcomes in IBD. Methods: This retrospective, single-center study included patients with Crohn’s disease (CD; n = 100), ulcerative colitis (UC; n = 120), and healthy controls (n = 80). Immunohistochemistry was used to assess the expression and subcellular localization of occludin and claudin-1 separately in surface (SE) and crypt epithelium (CR), with staining classified as predominantly membranous (regular) or cytoplasmic (irregular). The primary endpoint was IBD-related hospitalization. Secondary endpoints included surgery, initiation of biologic therapy, and clinical relapse. Logistic and Cox regression models were applied, and longitudinal changes were assessed in paired biopsies. Results: Both occludin and claudin-1 were dysregulated in active disease, showing increased expression and cytoplasmic redistribution compared with remission and controls. TJ alterations were more pronounced in the CR and correlated with clinical, endoscopic, and histological activity. In CD, occludin CR overexpression was independently associated with hospitalization (aOR 1.010; p = 0.05) and surgery (aHR 1.013; p = 0.005), while irregular occludin CR staining was associated with initiation of biologic therapy (aOR 3.48; p = 0.03). In UC, increased occludin CR levels and irregular CR staining were associated with IBD-related hospitalization in multivariable analyses (aOR 1.014; p = 0.035 and aOR 2.78; p = 0.032, respectively). Higher occludin CR levels identified UC patients at increased risk of clinical relapse (aHR 1.012; p = 0.002). In paired biopsies (n = 127), TJ architecture—particularly in the CR—improved over time, with reduced expression and a shift toward membranous localization, most prominently in bio-experienced patients. Conclusions: TJ remodeling, particularly crypt-level occludin dysregulation, is associated with disease activity and clinical outcomes, capturing a clinically relevant dimension of epithelial barrier dysfunction in IBD.