Checkpoint kinase 2 is a moderate-penetrance cancer susceptibility gene associated with increased colorectal cancer risk. Recent guideline updates recommend average-risk colorectal cancer screening for carriers; however,...Checkpoint kinase 2 is a moderate-penetrance cancer susceptibility gene associated with increased colorectal cancer risk. Recent guideline updates recommend average-risk colorectal cancer screening for carriers; however, real-world colonoscopy data remain limited. We performed a retrospective review of individuals with confirmed pathogenic or likely pathogenic checkpoint kinase 2 variants identified through an institutional hereditary cancer registry from 2011 to 2024. Colonoscopy and pathology reports were analyzed for demographics, cancer history, bowel preparation quality, and polyp characteristics including number, size, histology, and location. Among 144 patients undergoing 154 colonoscopies, median age at examination was 54 years. Polyps were identified in 51% of patients. Tubular adenomas were most common (28.6%), followed by hyperplastic polyps (18.3%) and sessile serrated lesions (10.4%). Advanced neoplasia, defined using conventional advanced adenoma-based criteria (size > 1 cm, villous features, high-grade dysplasia, or classified as intramucosal or invasive carcinoma) as well as including sessile serrated lesions ≥1 cm, were identified in 4.6%. Polyps measuring at least 1 centimeter were observed in 7.1%, and colorectal cancer was diagnosed in 1.3%. Proximal-only polyps were identified in 22.1% of examinations. Detection of tubular adenomas and proximal lesions increased with successive colonoscopies. This single-center experience demonstrates a moderate polyp burden with low rates of advanced neoplasia and colorectal cancer, supporting current recommendations for average-risk screening while highlighting the relevance of careful proximal examination.
Michalak A, Zawada I, Deskur A
… +24 more, Kopertowska-Majchrzak M, Talar-Wojnarowska R, Domżał-Magrowska D, Eder P, Stawczyk-Eder K, Waszak K, Rydzewska-Wyszkowska G, Maciejewska K, Karłowicz K, Gąsiorowska A, Kaczka A, Konecki Ł, Krogulecki M, Filipiuk A, Kłopocka M, Liebert A, Hartleb M, Gawron-Kiszka M, Poniewierka E, Gromny I, Zagórowicz E, Filip R, Majewska E, Cichoż-Lach H
Can J Gastroenterol Hepatol
· 2026 · PMID 42227576
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BACKGROUND: Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal disorders that significantly impact patients' quality of life (QoL). While clinical trials support the efficacy and safety of vedolizumab,...BACKGROUND: Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal disorders that significantly impact patients' quality of life (QoL). While clinical trials support the efficacy and safety of vedolizumab, real-world data linking its effectiveness to QoL-related patient-reported outcomes remain limited. This prospective observational study assessed the effects of 14-week vedolizumab induction therapy on QoL (i.e., fatigue, mood, and sleep disturbances), clinical response, safety, and predictors of response. METHODS: A total of 257 patients with ulcerative colitis (UC; n = 205) and Crohn's disease (CD; n = 52) received 14-week vedolizumab induction therapy. Disease activity, QoL (assessed using the total Inflammatory Bowel Disease Questionnaire [IBDQ]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), mood and sleep disturbances (PROMIS Depression and Sleep Disturbance scales), and selected biomarkers were evaluated. Clinical response was assessed using the Mayo score for UC and Crohn's Disease Activity Index (CDAI) score for CD. RESULTS: At Week 14, clinical response was observed in 82% of UC patients and 82.7% of CD patients. Median total IBDQ scores increased by 45.0 points in UC and 31.5 points in CD (p < 0.001). Median prorated FACIT-Fatigue scores increased by 5.0 points in both groups (p < 0.001), while median prorated PROMIS Sleep Disturbance and Depression T-scores decreased (p < 0.05). Improvement in QoL was moderately correlated with clinical response (r = 0.5). In logistic regression analysis, baseline patient characteristics indicative of advanced disease were associated with a reduced likelihood of clinical and QoL response to treatment. A total of 28 adverse events were reported, including 11 serious events and four treatment-related events. CONCLUSIONS: Vedolizumab reduced disease activity and led to a rapid improvement in QoL during the 14-week induction therapy in patients with IBD. Clinical response was positively correlated with QoL improvement. Predictors of reduced response were consistent with features of advanced disease.
Dubois-Laforgue D, Donadille B, Ciangura C
… +32 more, Amouyal C, Arnoux JB, Barat P, Baron S, Beltrand J, Bismuth E, Bouché C, Carel JC, Cavé H, Christin-Maitre S, Collin-Chavagnac D, Damgé C, Delemer B, Gourdy P, Jacqueminet S, Janmaat S, de Kerdanet M, Kessler L, Langin D, Nault JC, Nizard J, Polak M, Reynaud R, Saint-Martin C, Tauveron I, Valéro R, Vambergue A, Vantyghem MC, Vatier C, Nicolino M, Bellanné-Chantelot C, Vigouroux C
Orphanet J Rare Dis
· 2026 Mar · PMID 42227416
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MODY (Maturity-Onset Diabetes of the Young) is characterized by autosomal dominant mode of inheritance, early onset of diabetes in the absence of autoimmunity directed to pancreatic β-cells, impaired insulin secretory ca...MODY (Maturity-Onset Diabetes of the Young) is characterized by autosomal dominant mode of inheritance, early onset of diabetes in the absence of autoimmunity directed to pancreatic β-cells, impaired insulin secretory capacity, however, maintained over time, and extra-pancreatic manifestations in some patients. Its prevalence has been estimated 0.6% to 6.5% of all diabetes in Europe and the USA. Pathogenic variants in the genes encoding glucokinase or transcription factors HNF1A or HNF4A are responsible for the majority of cases of monogenic forms of diabetes referred to as MODY. The objective of the French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins) dedicated to GCK-MODY (formerly MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1) is to provide to health professionals a guide for optimal management and care of patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Thorough analysis of personal and family history, clinical examination and biochemical testing are key to raise the diagnosis, which has to be confirmed by molecular analysis. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. Overall, the management of patients with MODY requires the collaboration of several health care providers.
Wang YC, Liu KM, Gan YL
… +26 more, Chi NF, Lu LS, Chou CY, Wang LY, Chang LH, Hou MC, Fu YC, Chiou JF, Wu MS, Yang SF, Pang ST, Wang JY, Tsai YT, Huang CY, Chiu KM, Chen M, Chiang FT, Wang CH, Yao WJ, Lee SL, Huang CH, Liu YT, Wang SJ, Ko WY, Chen CH, Lee IH
BACKGROUND AND OBJECTIVES: Genome-wide association studies (GWASs) have identified common genetic risk loci for ischemic stroke (IS), primarily in European populations older than 55 years. We aimed to identify common and...BACKGROUND AND OBJECTIVES: Genome-wide association studies (GWASs) have identified common genetic risk loci for ischemic stroke (IS), primarily in European populations older than 55 years. We aimed to identify common and rare risk variants associated with early-onset IS (ages 18-54) in Taiwan. METHODS: We conducted GWASs of early-onset and all IS cases, compared with stroke-free controls of Han ethnicity, using the Taiwan Precision Medicine Initiative database, which includes individuals from general outpatient clinics across 16 medical centers. To explore the functional relevance of stroke-associated variants, we investigated fine-mapping and linkage disequilibrium patterns, phenotype correlations using the TOAST etiologic classification in an independent IS cohort, phenome-wide association studies (PheWASs), and pathway enrichment analysis. Furthermore, we examined rare pathogenic variants using whole-exome sequencing in consecutive, unrelated early-onset sporadic and/or familial stroke probands. RESULTS: We identified a robust association between a novel risk locus and early-onset IS (5,546 cases vs 143,017 controls; mean age: 52.7 vs 40.6 years; female: 45.6% vs 58.7%), including the lead single-nucleotide polymorphism (SNP) rs541118668 () (OR 1.69, 95% CI 1.44-1.98; = 6.86 × 10). In patients with all IS (21,544 cases vs 267,198 controls; mean age: 69.5 vs 53.7 years; female: 43.2% vs 55.5%), this locus and 6 other loci, including the reported rs12509595 (near ) (OR 1.06, 95% CI 1.04-1.08; = 2.74 × 10) in East Asians, were significantly associated. The novel SNPs clustered on chromosome 19p13.12 and were associated with the small vessel occlusion (SVO) subtype in the independent IS cohort (n = 716, < 0.05). The PheWASs of the risk variants revealed explicit associations with cerebrovascular diseases and no associations with other diseases. The enrichment pathway implicated in lipid metabolism and inflammatory responses. Moreover, we discovered that 28 of 180 unrelated probands with early-onset IS (15.6%; 16/85 sporadic and 12/87 familial stroke) carried likely pathogenic variants, particularly those with SVO ( and ) and cerebral venous infarction ( and ). DISCUSSION: Our study identifies a novel age-specific genetic hotspot for IS at chromosome 19p13.12 in Han Chinese. Together with enrichment of subtype-specific rare pathogenic variants, these findings reveal a distinct genetic architecture underlying early-onset stroke in East Asians.
Lee KJ, Fan GH, Huang A
… +2 more, Karagozian R, Almeqdadi M
Medicine (Baltimore)
· 2026 May · PMID 42216325
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Among unhoused individuals, alcohol use significantly contributes to the burden of liver disease. This study examines the effects of being unhoused on hospital outcomes and associated psychiatric conditions with alcohol-...Among unhoused individuals, alcohol use significantly contributes to the burden of liver disease. This study examines the effects of being unhoused on hospital outcomes and associated psychiatric conditions with alcohol-associated liver disease (ALD). We conducted a retrospective cohort study of adults hospitalized with ALD from 2020 to 2024 at a tertiary care center. Patients were stratified into housed (reference) and unhoused (exposure) cohorts. Multivariable regression analyses were performed to evaluate the association between housing status and clinical outcomes, using logistic regression for categorical outcomes and negative binomial regression for count outcomes. A total of 3523 patients, 330 unhoused and 3193 housed, were included. Unhoused patients were younger, more often male, and had lower body mass index (all P < .001). Unhoused patients had significantly more hospital admissions (3.65 ± 0.23 vs 2.46 ± 0.06; adjusted incidence rate ratio [aIRR] 1.62, 95% confidence interval [CI] 1.46-1.79, P < .001), greater total days hospitalized (22.35 ± 1.62 vs 15.91 ± 0.51; aIRR 1.60, 95% CI 1.42-1.82, P < .001), and more emergency department visits (10.11 ± 0.70 vs 2.21 ± 0.07; aIRR 4.89, 95% CI 4.18-5.74, P < .001) and intensive care unit visits (0.23 ± 0.03 vs 0.13 ± 0.01; aIRR 1.62, 95% CI 1.22-2.12, P < .001). Mortality and average length of stay per encounter did not differ. Unhoused patients had higher odds of hepatic encephalopathy (adjusted odd ratio [aOR] 1.38, 95% CI 1.04-1.83, P = .02), malnutrition (aOR 1.79, 95% CI 1.38-2.31, P < .001), and sepsis (aOR 2.13, 95% CI 1.61-2.81, P < .001). Substance use and psychiatric comorbidities were more prevalent among unhoused patients. Being unhoused is associated with greater hospital utilization and complications among patients with ALD, underscoring the need for integrated medical, addiction, psychiatric, and social-support interventions.
BACKGROUND: Liver cirrhosis complicated by sepsis is associated with significant immune dysfunction and high mortality rates. Programmed cell death protein 1 (PD-1) expression on lymphocytes has been implicated in immune...BACKGROUND: Liver cirrhosis complicated by sepsis is associated with significant immune dysfunction and high mortality rates. Programmed cell death protein 1 (PD-1) expression on lymphocytes has been implicated in immune exhaustion, but its prognostic significance in this population remains unclear. OBJECTIVE: This study aimed to evaluate the prognostic value of lymphocyte PD-1 expression in combination with clinical scoring systems, such as the Child-Pugh score and chronic liver failure-sequential organ failure assessment (CLIF-SOFA), for predicting disease severity and 28-day mortality in patients with cirrhosis complicated by sepsis. METHODS: This prospective study included 86 patients with cirrhosis and sepsis admitted to Beijing You'an Hospital between June 2023 and May 1, 2024. Fresh whole blood was collected at enrollment, and peripheral blood mononuclear cells (PBMCs) were isolated for flow cytometric analysis of PD-1 expression on CD3+, CD4+, and CD8+ lymphocytes. Clinical parameters, scoring systems, and laboratory data were collected to assess their correlation with PD-1 expression and patient outcomes. RESULTS: Of the 86 patients, 38 (44.2%) survived, while 48 (55.8%) died within 28 days. Non-survivors exhibited higher PD-1 expression on CD3+, CD4+, and CD8+ lymphocytes, as well as worse Child-Pugh and CLIF-SOFA scores (all p < 0.05). A significant positive correlation was observed between lymphocyte PD-1 expression and disease severity scores. Multivariate logistic regression analysis identified PD-1 expression on CD3+, CD4+, and CD8+ lymphocytes as independent predictors of 28-day mortality. Combining lymphocyte PD-1 expression with clinical scoring systems improved the predictive accuracy for septic shock and mortality. CONCLUSION: Lymphocyte PD-1 expression is associated with disease severity and poor prognosis in patients with cirrhosis complicated by sepsis. Combining PD-1 expression with traditional scoring systems enhances risk stratification and may provide a more comprehensive tool for predicting outcomes in this high-risk population.
BACKGROUND: Improved long-term outcomes after pediatric liver transplantation (LT) necessitate a holistic approach to care that addresses physical, mental, and social-emotional health. The Pediatric Liver Transplant Qual...BACKGROUND: Improved long-term outcomes after pediatric liver transplantation (LT) necessitate a holistic approach to care that addresses physical, mental, and social-emotional health. The Pediatric Liver Transplant Quality of Life Questionnaire (PeLTQL) is a disease-specific Patient-Reported Outcome Measure (PROM) with self- and proxy-versions available; higher scores indicate better health-related quality of life (HRQOL), and scores ≤ 62.5 denote anxiety risk. Limited data exist on specific patient concerns and dyad discrepancies in disease-specific PROMs for pediatric LT recipients. This study aimed to examine self- and proxy-PeLTQLs, factors influencing discrepancies, and their relationship to anxiety risk in pediatric LT recipients. METHODS: Retrospective cohort review of all pen-paper PeLTQLs completed by patient-parent dyads (2013-2022). Clinical, laboratory, and radiologic data were recorded. RESULTS: PeLTQLs from 140 dyads were analyzed (median patient age at PeLTQL completion 11.1 years, 48% male, 55% Caucasian and 44% Biliary Atresia). Twenty-two percent of patients were identified as "at-risk" for anxiety expressing larger concerns about their scar (61% vs. 27%, p < 0.001) and future health (74% vs. 13%, p < 0.001). Overall median self- and proxy PeLTQL scores were similar (73 vs. 72.1, p = 0.7) but agreement was poor (ICC 0.44). Parents of at-risk for anxiety patients underestimated their child's concerns (median self 52.1 vs. proxy 66, p < 0.001) principally about their future health. CONCLUSION: Integrating HRQOL assessment into routine surveillance care for pediatric LT recipients can identify anxiety risk and specific concerns in pediatric LT recipients. Poor patient-proxy agreement underscores the need to listen to the patient voice to optimize patient-centered care.
Scheepens JCM, Prinsze KJ, van Geest LG
… +26 more, Besselink MG, Bonsing BA, Bruynzeel AME, Cirkel GA, Heerkens HD, de Hingh IH, Homs MYV, van Hooft JE, van Laarhoven HWM, Leeuwenburgh LC, de Meijer VE, Meijer GJ, Molenaar IQ, Noordzij PG, Peulen HMU, van Santvoort HC, Stommel MWJ, Verdonk RC, Vissers PAJ, van Vliet C, de Vos-Geelen J, Wilmink JW, Intven MPW, Daamen LA, Grimbergen G, Dutch Pancreatic Cancer Group
Eur J Cancer
· 2026 Jun · PMID 42208281
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BACKGROUND: Pancreatic cancer has a poor prognosis. Multiple treatment modalities are available, their impact on health-related quality of life (HRQoL) and overall survival (OS) in older patients remains unclear. This st...BACKGROUND: Pancreatic cancer has a poor prognosis. Multiple treatment modalities are available, their impact on health-related quality of life (HRQoL) and overall survival (OS) in older patients remains unclear. This study compared HRQoL, postoperative mortality, adjuvant chemotherapy use and OS after various treatment strategies between elderly and younger patients with localized pancreatic cancer. METHODS: In this nationwide cohort study (2015-2023), patients with localized pancreatic cancer (resectable, borderline resectable and locally advanced disease) treated with surgical resection, chemotherapy alone, or stereotactic body radiation therapy (SBRT) were included and stratified into elderly (≥75years) and younger (<75years). The primary outcome was HRQoL assessed with the EORTC QLQ-C30. Secondary outcomes included OS, 90-day mortality, and adjuvant chemotherapy. Linear mixed models with Bonferroni correction (p < 0.013) evaluated HRQoL. Logistic regression assessed 90-day mortality and adjuvant chemotherapy. OS was analyzed using Cox proportional hazards models. RESULTS: 5217 patients were included (3496 resection, 1459 chemotherapy-only, and 262 SBRT). Following resection, elderly reported less dyspnea at 0-3 months but worse role functioning, more fatigue and pain at 9-12 months. No differences were observed between patients treated with chemotherapy only. Elderly patients had higher 90-day postoperative mortality (adjusted OR:1.6, 95%CI[1.2-2.23],p = 0.003) and were less likely to receive adjuvant chemotherapy (adjusted OR:0.4, 95%CI[0.3-0.4],p < 0.001). Age was not independently associated with OS across treatment groups. CONCLUSION: Elderly patients reported comparable longitudinal HRQoL as to younger patients. Higher age was associated with higher 90-day mortality and less use of adjuvant chemotherapy, but it was not independently associated with overall survival. These findings support individualized shared decision-making and suggest that age alone should not preclude treatment.
BACKGROUND AND AIMS: Early identification by gastroenterologists of peritonitis in acute appendicitis may support timely decision-making when clinical assessment and imaging are equivocal. The aim of this study was to as...BACKGROUND AND AIMS: Early identification by gastroenterologists of peritonitis in acute appendicitis may support timely decision-making when clinical assessment and imaging are equivocal. The aim of this study was to assess the diagnostic and predictive value of routinely available laboratory parameters and systemic inflammatory indices in identifying peritonitis among patients undergoing surgery for acute appendicitis. By integrating clinical features, biochemical markers and composite hematological ratios, this study seeks to contribute to improved risk stratification and early decision-making in patients with acute appendicitis. METHODS: We conducted a single-center retrospective observational study of adults (≥18 years) undergoing appendectomy for acute appendicitis (July 2023-July 2024). Patients were stratified by intraoperatively confirmed peritonitis. Admission biomarkers and complete hemogram-derived indices were evaluated using ROC analysis (AUC; Youden cut-offs). Multivariable logistic regression models were adjusted for age, gender, time from symptom onset to surgery, and Alvarado score. RESULTS: Among the 99 patients included, 52 (52.5%) had peritonitis. Compared with patients without peritonitis, those with peritonitis had a higher median age, body mass index (BMI), Alvarado score, and C-reactive protein (CRP) level. CRP showed the highest discriminatory ability for identifying peritonitis (AUC=0.713, 95%CI: 0.613-0.813), with a cut-off value of 15.1 mg/L, corresponding to a sensitivity of 70.6% and a specificity of 70%. Hemogram-derived inflammatory indices demonstrated moderate discriminatory performance for predicting peritonitis, including the monocyte-to-lymphocyte ratio (MLR; AUC=0.680; cut-off ≥0.653), eosinophil count (AUC=0.663; cut-off 0.035×10⁹/L) for predicting the absence of peritonitis, the systemic inflammation response index (SIRI; AUC=0.657; cut-off ≥7.42), and the neutrophil-to-lymphocyte ratio (NLR; AUC=0.647; cut-off ≥10.855). In adjusted models, MLR ≥0.653 (aOR=6.92, 95%CI: 2.55-21.21), SIRI ≥7.42 (aOR=6.89, 95%CI: 2.46-22.29), and NLR ≥10.855 (aOR=5.88, 95%CI: 2.16-18.13) were associated with increased odds of peritonitis, whereas eosinophil count ≥0.035×10⁹/L was inversely associated with peritonitis (aOR=0.22, 95%CI: 0.08-0.54). CONCLUSIONS: Hemogram-derived inflammation indices, particularly MLR, SIRI, and NLR, are independently associated with intraoperative peritonitis and may complement CRP for preoperative risk stratification. Prospective multicenter validation is warranted to confirm thresholds and clinical utility.
BACKGROUND AND AIMS: Steatotic liver disease (SLD) has emerged as an important risk factor for hepatocellular carcinoma (HCC), often in the absence of cirrhosis. We aimed to develop explainable machine learning (ML) mode...BACKGROUND AND AIMS: Steatotic liver disease (SLD) has emerged as an important risk factor for hepatocellular carcinoma (HCC), often in the absence of cirrhosis. We aimed to develop explainable machine learning (ML) models to predict HCC risk in individuals with SLD using routinely collected screening data. METHODS: Using the Korean National Health Insurance Service database, we included adults aged 20-79 years who underwent national health screening in 2017. SLD was defined as a fatty liver index (FLI) ≥ 60. Multiple ML algorithms, including deep learning models, were trained using a 7:3 train-test split with repeated non-replacement undersampling at a 1:3 case-to-control ratio to address extreme class imbalance. RESULTS: Among 1,241,560 adults with SLD, 2,152 (0.17%) developed HCC during a 6-year follow-up period. In the internal validation cohort, the final weighted multi-head attention deep neural network ensemble achieved an area under the receiver operating characteristic curve of 0.923, with a sensitivity of 71.36% and specificity of 93.65%. SHapley Additive exPlanations consistently identified age, sex, triglycerides, total cholesterol, aminotransferases, gamma-glutamyl transferase (GGT), Charlson Comorbidity Index, and FLI as key contributors to HCC risk. In multivariable Cox models, older age, male sex, elevated GGT, higher aspartate aminotransferase and FLI, and greater comorbidity burden were positively associated with HCC risk, whereas higher triglyceride and total cholesterol levels were inversely associated. Model-based risk stratification identified four groups with distinct HCC-free survival curves; the extremely high-risk group had an approximately 74.9-fold higher hazard of HCC than the low-risk group (95% CI, 55.3-101.5). CONCLUSIONS: Overall, this explainable ML model based on routine health screening variables enables robust HCC risk stratification and may help inform future targeted surveillance strategies in SLD populations after external validation.
Li XX, Zhang YQ, Wang SJ
… +4 more, Gao ZX, Xie Y, Li MH, Gao YJ
Biomed Environ Sci
· 2026 May · PMID 42205022
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OBJECTIVE: To investigate risk factors associated with significant histologic lesions in metabolic dysfunction-associated steatotic liver disease (MASLD) using the SAF (Steatosis, Activity, Fibrosis) scoring system and t...OBJECTIVE: To investigate risk factors associated with significant histologic lesions in metabolic dysfunction-associated steatotic liver disease (MASLD) using the SAF (Steatosis, Activity, Fibrosis) scoring system and to develop a risk prediction model. METHODS: In this retrospective cohort of 415 biopsy-proven MASLD patients (2018-2022), participants were stratified into significant lesion (SAF activity grade ≥ 3 and/or fibrosis stage ≥ 3, = 131) and non-significant lesion (activity < 3 and fibrosis < 3, = 284) groups. Demographic, laboratory, and imaging parameters including platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), total bile acids (TBA), triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), uric acid (UA), laminin (LN), hyaluronic acid (HA), procollagen type III (PC-III), collagen type IV (C-IV), controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) were analyzed. RESULTS: Patients with significant lesions had higher body mass index (BMI), proportion of high-fat diet, AST, ALT, TBA, UA, CAP, and LSM (all < 0.05). Multivariate logistic regression identified BMI ( = 1.182), UA ( = 1.003), CAP ( = 1.005), and LSM ( = 1.104) as independent predictors of significant histologic lesions, with a model area under the curve of 75.18%. CONCLUSION: BMI, hyperuricemia, hepatic steatosis (CAP), and fibrosis (LSM) are independent risk factors for advanced MASLD. A combined non-invasive assessment may enhance risk stratification in clinical practice.
Silva de Albuquerque Júnior J, Cardoso AC, Araújo Dos Santos Júnior J
… +4 more, Spara Gadelha P, Dos Santos Amaral R, Herrero Fernández Z, Marques do Nascimento Santos J
Biomed Phys Eng Express
· 2026 Jun · PMID 42202822
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This scoping review maps the landscape of quantitative ultrasound (QUS) techniques for hepatic fat assessment, emphasizing their physical principles, signal-processing strategies, technological implementations, reference...This scoping review maps the landscape of quantitative ultrasound (QUS) techniques for hepatic fat assessment, emphasizing their physical principles, signal-processing strategies, technological implementations, reference standards, and sources of variability, and highlights their potential to advance noninvasive liver imaging in metabolic dysfunction-associated steatotic liver disease (MASLD).Following JBI methodology and reporting in accordance with the PRISMA-ScR checklist, a comprehensive search was conducted in PubMed, MEDLINE, ScienceDirect, and Scopus for studies published from January 2010 to October 2025. Human studies evaluating QUS-based methods for hepatic fat quantification in the context of MASLD were included. Screening and data extraction were performed using standardized procedures, with iterative refinement of the data-charting framework.Out of 1 265 identified records, 150 studies were included. The body of literature has evolved from initial proof-of-concept and signal-processing investigations to more recent research emphasizing clinical relevance, reproducibility, and real-world use. Publication activity rose significantly after around 2018, coinciding with the commercial release of QUS technologies. The most common methods were based on attenuation coefficients, followed by approaches using backscattering coefficients, speed-of-sound estimation, envelope statistics, and combined multiparametric techniques. Recently, MRI- proton density fat fraction has become the preferred reference standard in validation studies, whereas liver biopsy and the controlled attenuation parameter have been used less often as primary comparison methods.Hepatic QUS is a diverse and rapidly evolving field encompassing multiple methodological categories grounded in distinct physical principles. Although QUS offers a physically grounded and clinically promising framework for noninvasive hepatic fat assessment, substantial heterogeneity in acquisition protocols, implementation, and reporting limits comparability across platforms. Greater standardization, improved inter-manufacturer reproducibility, and further development of robust multiparametric approaches are essential to enhance its clinical utility in the management of MASLD.
Cylwik B, Gan K, Kazberuk M
… +5 more, Gruszewska E, Panasiuk A, Sienkiewicz M, Wojtkowska M, Chrostek L
Int J Mol Sci
· 2026 May · PMID 42196173
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This study evaluated the diagnostic usefulness of surfactant protein D (SP-D), chemokine C-C motif ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and interleukin 18 (IL-18) in patients with SARS-CoV-2 infectio...This study evaluated the diagnostic usefulness of surfactant protein D (SP-D), chemokine C-C motif ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and interleukin 18 (IL-18) in patients with SARS-CoV-2 infection. The authors focused on lung failure assessment, lung parenchyma involvement, and the early assessment of the risk of developing pulmonary fibrosis at the onset of COVID-19. The study group included 87 patients with COVID-19 and 45 healthy subjects. Concentrations of all three markers were measured using the enzyme immunoassay method. The serum SP-D, CCL2/MCP-1, and IL-18 concentrations were significantly higher in the COVID-19 patients before admission to the hospital than those in the controls ( < 0.001 for all comparisons). Differences were only found in the IL-18 levels between the groups categorized according to disease severity ( < 0.001); levels were significantly higher in patients with critical disease severity compared to those with moderate disease severity ( < 0.001). IL-18 also showed a positive correlation with the disease severity ( = 0.025). SP-D and IL-18 levels varied depending on the amount of oxygen administration ( = 0.017 and < 0.001, respectively). Among the blood gas parameters, SP-D levels were negatively associated with the partial pressure of arterial oxygen (PaO) and oxygen saturation (OSat) ( = 0.026 and = 0.048, respectively), IL-18 with OSat ( = 0.036), and CCL2/MCP-1 with PaO ( = 0.042). SP-D and IL-18 were significantly negatively correlated with oxygen therapy ( = 0.003 and = 0.014, respectively). Conversely, CCL2/MCP-1 was significantly positively correlated with the pulmonary involvement severity ( = 0.017) and level of hyaluronic acid (HA), a marker of fibrosis ( = 0.042). We also observed a significant correlation between the IL-18 level and the pulmonary involvement severity ( < 0.001), HA ( < 0.001), and other markers of fibrosis. In summary, our study's results indicate that SP-D, CCL2/MCP-1, and IL-18 may be used to assess lung function in the early stage of COVID-19 infection; additionally, SP-D may serve as an indicator of alveolar injury, while CCL2/MCP-1 and IL-18 may be markers of lung parenchyma involvement and potential predictors of the development of pulmonary fibrosis.
Wu CH, Lin ML, Wang CY
… +9 more, Chang CY, Lee FJ, Cheng ML, Lin YS, Chen TW, Hsiao YT, Wang BW, Kuo CS, Huang RS
Int J Mol Sci
· 2026 May · PMID 42196170
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Inadequate choline intake-induced choline metabolic stress (CMS) has been divergently linked to metabolic dysfunction-associated steatotic liver disease (MASLD), yet underlying mechanisms remain unclear. We hypothesized...Inadequate choline intake-induced choline metabolic stress (CMS) has been divergently linked to metabolic dysfunction-associated steatotic liver disease (MASLD), yet underlying mechanisms remain unclear. We hypothesized that CMS modifies plasma-free amino acid (PFAA) signatures to influence MASLD risk. In a nested case-control study of 125 participants, dietary choline intake and blood choline metabolites were assessed together with targeted metabolomics and transcriptomic profiling. MASLD was characterized by low choline intake, reduced plasma betaine/choline ratio (Pbcr), elevated homocysteine, increased branched-chain amino acids (BCAAs), and depleted serine/glycine, achieving strong predictive accuracy (AUC = 0.90). CMS was associated with reduced lymphocytic transcripts involved in BCAA catabolism and altered mTORC1/Akt/IRS1 signaling. Nonlinear Pbcr- and intake-dependent MASLD risk patterns were attenuated after adjustment for genetic-metabolite networks. These findings identify CMS-responsive metabolic mediators supporting precision choline interventions.
Medicina (Kaunas)
· 2026 Apr · PMID 42195068
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Early identification of patients at risk for severe forms of acute cholangitis (AC) is crucial for guiding prompt therapeutic interventions. In addition to traditional biomarkers such as C-reactive protein (CRP), newer i...Early identification of patients at risk for severe forms of acute cholangitis (AC) is crucial for guiding prompt therapeutic interventions. In addition to traditional biomarkers such as C-reactive protein (CRP), newer indices like the neutrophil-to-lymphocyte ratio (NLR) are cost-effective and easy-to-use diagnostic tools. In the context of limited evidence from Eastern European populations, this study aimed to compare the performance of NLR and CRP in identifying organ dysfunction-based severe presentation of acute cholangitis according to a modified TG18-derived classification. We conducted a retrospective study including patients admitted to Colentina Clinical Hospital between January 2021 and September 2025. Demographic, clinical, and laboratory data were collected from medical records, with a focus on admission inflammatory biomarkers: NLR and CRP. Symptom onset-to-presentation time was not recorded. Patients were stratified by disease severity according to a modified organ dysfunction-based severity classification, and comparative statistical analysis, including Receiver Operating Characteristic (ROC) curve analysis, was performed to assess the diagnostic performance and optimal cut-off values of both biomarkers for severe clinical presentation. A total of 364 patients were included, with a median age of 68 years (IQR: 60-78), and a slight female predominance (55.5%). Of these, 231 were classified as non-severe and 133 as severe. Both CRP and NLR were significantly higher in severe cases ( = 0.042 and = 0.018, respectively. Despite statistical significance, CRP showed limited discriminatory ability, whereas NLR showed only a marginal numerical advantage. ROC analysis showed poor discriminatory ability for both CRP (AUC = 0.564, 95% CI 0.503-0.624, = 0.042) and NLR (AUC = 0.574, 95% CI 0.513-0.635, = 0.018) in predicting severe AC incidence. The difference between AUCs was minimal (ΔAUC = 0.010, 95% CI -0.062 to 0.082, = 0.78, DeLong test). Both CRP and NLR showed limited discriminatory performance in identifying organ dysfunction-based severe presentation of acute cholangitis. The small, non-significant difference between the two markers does not support a meaningful comparative advantage, and neither biomarker appears suitable for reliable early risk stratification on its own.
Hernández-Gea V, Paradis V, Guindi M
… +28 more, Alves VAF, Aqul A, Cerda E, Darwish Murad S, Das P, Di Giorgio A, de Freitas LAR, Grammatikopoulos T, Harada K, Hernandez N, Ibrahim SH, Kakar S, Karpen S, Kleiner DE, Ormeci N, Qi X, Sakhuja P, Schinoni MI, Saxena R, Sayadi A, Shukla A, Tiniakos DG, Verna E, Wong K, Elkrief L, Sempoux C, Heller T, Rautou PE
Non-cirrhotic portal hypertension has historically been described using heterogeneous and region-specific terminology, such as idiopathic portal hypertension (IPH), non-cirrhotic portal fibrosis (NCPF), obliterative port...Non-cirrhotic portal hypertension has historically been described using heterogeneous and region-specific terminology, such as idiopathic portal hypertension (IPH), non-cirrhotic portal fibrosis (NCPF), obliterative portal venopathy, and nodular regenerative hyperplasia, leading to substantial variability in diagnosis, reporting, and international research collaboration. Differences in guideline definitions from major societies (AASLD, EASL, and APASL), together with the presence of characteristic histologic lesions in patients without clinically overt portal hypertension, have further complicated disease classification. To address these challenges, a large, multisociety, international initiative was convened to harmonize nomenclature and diagnostic criteria. Representatives from liver, pathology, and pediatric hepatology societies across the Americas, Europe, and Asia participated in a structured consensus process that included specialized working groups and external Delphi validation. The initiative produced a globally harmonized and implementable diagnostic framework. Consensus was reached that the terms porto-sinusoidal vascular disorder (PSVD) and NCPF may be used interchangeably when identical diagnostic criteria are applied, and that they should be written as PSVD or NCPF. The diagnosis was defined as fundamentally clinicopathological, requiring integrated assessment. Core principles include the need for a high-quality liver biopsy (≥10 mm), mandatory exclusion of cirrhosis, and systematic exclusion of specific alternative conditions. Importantly, the consensus recognizes that PSVD or NCPF may be diagnosed even without clinical portal hypertension and may coexist with other liver diseases, provided cirrhosis is excluded. Standardized major and minor histologic criteria were developed collaboratively by expert pathologists and externally validated. Features of portal hypertension were harmonized into specific and nonspecific categories applicable to routine clinical practice. An integrated diagnostic scoring system incorporating histology, clinical features, associated conditions, and concommitant etiologies was developed and validated using the Delphi method. This consensus provides the first internationally endorsed, unified framework for the diagnosis of PSVD or NCPF. Its global implementation is expected to reduce diagnostic variability, improve comparability across regions, and facilitate the development of robust, internationally harmonized clinical and translational research cohorts.