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15 pages, 899 KB  
Article
Enzalutamide Versus Abiraterone After Docetaxel in Metastatic Castration-Resistant Prostate Cancer: Real-World Outcomes and Exploratory Prognostic Stratification
by Mert Tohumcuoğlu, Tolga Köşeci, Alpay Düşgün, Abdullah Evren Yetişir, Cem Mirili, Burak Mete and Mahmut Büyükşimşek
J. Clin. Med. 2026, 15(12), 4816; https://doi.org/10.3390/jcm15124816 (registering DOI) - 21 Jun 2026
Abstract
Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with [...] Read more.
Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application. Full article
(This article belongs to the Section Oncology)
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25 pages, 1966 KB  
Article
Monocyte-Containing Inflammatory Indices Show Stronger Association with 30-Day Mortality than the Systemic Immune-Inflammation Index in Elderly Sepsis: A Single-Center Retrospective Observational Cohort Study
by Alexandru-Ionut Irimie, Sorin-Nicolae Dinescu, Marius-Bogdan Novac, Ramona-Constantina Vasile, Alexandra-Daniela Rotaru-Zavaleanu, Mihai-Andrei Ruscu and Lucretiu Radu
J. Clin. Med. 2026, 15(12), 4799; https://doi.org/10.3390/jcm15124799 (registering DOI) - 20 Jun 2026
Abstract
Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in [...] Read more.
Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in whom immunosenescence may alter the leukocyte phenotype, remains poorly characterized. Methods. In a single-center retrospective cohort of patients aged ≥65 years admitted to a tertiary ICU with Sepsis-3-defined sepsis (n = 127, 33 deaths), we compared the discrimination of six indices (NLR, PLR, MLR, SII, SIRI, AISI) for 30-day all-cause mortality using AUROC with bootstrap confidence intervals and pairwise DeLong tests. Independent associations were assessed by logistic regression adjusted for APACHE II and age; incremental value over APACHE II was explored using IDI, cNRI, calibration and decision curve analysis, with bootstrap optimism correction. Results. Thirty-day mortality was 26.0%. The monocyte-containing indices (AISI, SIRI, MLR) discriminated better than SII and NLR, and AISI was significantly superior to SII, NLR and PLR on DeLong testing, though not to SIRI, MLR or APACHE II. After adjustment for APACHE II and age, AISI, SIRI and MLR remained independently associated with mortality, whereas SII and PLR did not. Adding AISI to APACHE II improved reclassification and calibration and yielded higher net clinical benefit across clinically relevant thresholds. Conclusions. In this exploratory, single-center analysis, monocyte-containing indices, particularly AISI, were more strongly associated with 30-day mortality in elderly ICU sepsis than SII or NLR. AISI, SIRI and MLR were strongly intercorrelated and near-equivalent, and AISI did not significantly exceed APACHE II in discrimination. These hypothesis-generating findings require prospective external validation before clinical use. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
15 pages, 902 KB  
Article
Circulating Cell-Free DNA Analysis for Diagnostic and Prognostic Assessment of Hepatocellular Carcinoma in Cirrhosis
by Inés Aznar-Peralta, Amparo Roa-Colomo, Javier López Hidalgo, Cristobal Fresno, Valeria Denninghoff and María José Serrano
Int. J. Mol. Sci. 2026, 27(12), 5590; https://doi.org/10.3390/ijms27125590 (registering DOI) - 20 Jun 2026
Abstract
Early detection of hepatocellular carcinoma (HCC) is crucial for curative treatment, yet current screening strategies for high-risk liver cirrhosis (LC) patients lack sufficient sensitivity. This study evaluates plasma cell-free DNA(cfDNA) concentration and fragmentomics as biomarkers to improve HCC diagnosis and prognosis. Plasma samples [...] Read more.
Early detection of hepatocellular carcinoma (HCC) is crucial for curative treatment, yet current screening strategies for high-risk liver cirrhosis (LC) patients lack sufficient sensitivity. This study evaluates plasma cell-free DNA(cfDNA) concentration and fragmentomics as biomarkers to improve HCC diagnosis and prognosis. Plasma samples from 39 HCC and 46 LC patients were analyzed for cfDNA concentration and fragment patterns. A multivariate logistic regression model (CMAC), integrating cfDNA concentration, mononucleosome proportion (%MN), alpha-fetoprotein (AFP), and c-reactive protein (CRP), was developed and validated using Leave-One-Out Cross-Validation and bootstrapping. HCC patients exhibited significantly higher cfDNA concentrations (p < 0.0001) and longer fragment lengths (p < 0.05) compared to LC patients. The CMAC model demonstrated superior diagnostic performance (AUROC = 0.946) compared to AFP alone (AUROC = 0.777, p < 0.001). Notably, in early-stage HCC, the CMAC model remained highly accurate (AUROC = 0.941), whereas AFP failed to reach statistical significance. Higher CMAC scores were significantly associated with advanced BCLC stages (p = 0.009), lymphovascular invasion (p = 0.0063) and reduced overall survival (p = 0.0037). Integration of cfDNA analysis with established clinical markers in the CMAC model shows promise as a complementary tool for the early detection of HCC in LC patients. Validation in larger, multicenter cohorts will be necessary to confirm these findings and their clinical applicability. Full article
(This article belongs to the Special Issue Biomarkers in Oncology)
23 pages, 1901 KB  
Article
Prognostic Nutritional Index and In-Hospital Mortality After Coronary Artery Bypass Grafting: An Exploratory Analysis in Relation to Surgical Risk Scores
by Burak Toprak, Nihat Söylemez, Menaf Akın Sert, Özkan Karaca, Mustafa Ekici, Ali Orçun Sürmeli, Abdulkadir Bilgiç, Samet Yımaz, Sonay Oğuz, Mehmet Ballı and Rıdvan Bora
Nutrients 2026, 18(12), 2001; https://doi.org/10.3390/nu18122001 (registering DOI) - 20 Jun 2026
Abstract
Background: Coronary anatomical complexity is commonly used for perioperative risk assessment in patients undergoing coronary artery bypass grafting (CABG), although it may not fully reflect systemic biological vulnerability. This study aimed to evaluate the association between the Prognostic Nutritional Index (PNI), a nutritional–immune [...] Read more.
Background: Coronary anatomical complexity is commonly used for perioperative risk assessment in patients undergoing coronary artery bypass grafting (CABG), although it may not fully reflect systemic biological vulnerability. This study aimed to evaluate the association between the Prognostic Nutritional Index (PNI), a nutritional–immune marker derived from serum albumin and lymphocyte counts, and in-hospital mortality after CABG in relation to coronary anatomical complexity and established surgical risk scores. Methods: In this single-center retrospective cohort study, 324 consecutive patients who underwent isolated CABG between April 2024 and April 2025 were analyzed. The PNI was calculated according to the standard Onodera formula using preoperative serum albumin and total lymphocyte count. Associations with in-hospital mortality were evaluated using univariable and multivariable logistic regression analyses. Discriminative performance was assessed using receiver operating characteristic curve analysis, while exploratory analyses evaluating the additional prognostic contribution of the PNI beyond surgical risk scores were performed using nested model comparison and reclassification analyses. Internal validation and calibration analyses were also performed. Results: In-hospital mortality occurred in 26 patients. Preoperative and postoperative PNI values were significantly lower in patients who experienced in-hospital mortality. In multivariable analysis, the postoperative PNI remained independently associated with in-hospital mortality, whereas the preoperative PNI lost statistical significance after adjustment for clinical, renal, and surgical risk parameters. Receiver operating characteristic analysis demonstrated modest discriminative ability for the preoperative PNI (AUC: 0.742, 95% CI: 0.661–0.823). Exploratory analyses suggested a modest improvement in model discrimination and risk classification after the addition of the PNI to STS-based models; however, the overall incremental prognostic contribution remained limited. Calibration and internal validation analyses demonstrated acceptable agreement between predicted and observed mortality risk. Conclusions: The postoperative PNI demonstrated a stronger and independent association with in-hospital mortality than the preoperative PNI, suggesting that early postoperative nutritional–immune deterioration may reflect the magnitude of perioperative physiological stress and evolving clinical deterioration after CABG. Although lower preoperative PNI values were associated with mortality in univariable analyses, this association was no longer statistically significant after adjustment for clinical, renal, and surgical risk parameters. These findings indicate that postoperative nutritional–immune status may provide complementary biological information beyond conventional risk models; however, its clinical utility requires confirmation in larger prospective multicenter studies. Full article
(This article belongs to the Section Clinical Nutrition)
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14 pages, 2593 KB  
Article
Digital and Manual Assessment of Intrafollicular Ki-67, MYC, and p53 in Classic Follicular Lymphoma
by George C. de Castro, Morgan L. Shannon, Ruth Zhang, Kunwar Singh, Robert S. Ohgami and Kwun Wah Wen
Diagnostics 2026, 16(12), 1917; https://doi.org/10.3390/diagnostics16121917 (registering DOI) - 20 Jun 2026
Abstract
Background/Objectives: There remains a need for additional prognostic markers in classic follicular lymphoma (cFL) to identify aggressive disease. Immunohistochemical stains such as Ki-67, MYC, and p53 have shown variable associations with histologic grade and adverse outcomes. In this study, we aimed to [...] Read more.
Background/Objectives: There remains a need for additional prognostic markers in classic follicular lymphoma (cFL) to identify aggressive disease. Immunohistochemical stains such as Ki-67, MYC, and p53 have shown variable associations with histologic grade and adverse outcomes. In this study, we aimed to assess intrafollicular Ki-67, MYC, and p53 expression in cFL via immunohistochemistry, quantified by both manual and digital methods, and evaluate their relation to histologic grade and clinical outcomes. Methods: We evaluated 37 cases of cFL from 2000 to 2019 and performed immunohistochemistry for Ki-67, MYC, and p53 on tumor microarray tissue. Stains were assessed within follicles by digital pathology means on QuPath software and via manual low-power estimates. Results:MYC expression was greater in FL3A compared to FL1–2 across all digital and manual scoring methods (all p < 0.05). Ki-67 and p53 expression did not differ by histologic grade group. No biomarker showed a significant association with adverse clinicopathologic features or outcomes, including FLIPI risk group, bulky disease, clinical stage, event-free survival, or overall survival. Manual and digital scores demonstrated strong correlations for all markers (ρ = 0.71–0.89, all p < 0.001). Conclusions: In our cohort, MYC expression was increased in FL3A compared to FL1–2, while no intrafollicular biomarker measurement was associated with adverse clinicopathologic features or clinical outcomes in exploratory analyses. These findings should be interpreted with caution in light of our limited cohort size. Strong concordance between manual and digital scoring supports the feasibility of digital IHC quantification in cFL. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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16 pages, 2505 KB  
Article
Stroke Subtype as a Determinant of Mortality in Adult Patients on Extracorporeal Membrane Oxygenation
by Amir Mahdi Ghafarian, Ali Samani, Jawad Saad, Mohammad Ghafarian, Muaaz Wajahath, Sarah Foster, Seungwon Lim, Aliyah Sutton, Faddi G. Saleh Velez, Denise Battaglini and Andrea Loggini
J. Clin. Med. 2026, 15(12), 4790; https://doi.org/10.3390/jcm15124790 (registering DOI) - 20 Jun 2026
Abstract
Background: Stroke significantly increases morbidity and mortality in patients receiving extracorporeal membrane oxygenation (ECMO). This study evaluates the prognostic impact of stroke subtypes, acute ischemic stroke (AIS) and hemorrhagic stroke (HS), and neurologic injury severity in a contemporary adult population. Methods: We conducted [...] Read more.
Background: Stroke significantly increases morbidity and mortality in patients receiving extracorporeal membrane oxygenation (ECMO). This study evaluates the prognostic impact of stroke subtypes, acute ischemic stroke (AIS) and hemorrhagic stroke (HS), and neurologic injury severity in a contemporary adult population. Methods: We conducted a retrospective cohort study using the TriNetX federated electronic health record network, including adult patients who underwent ECMO between 1 October 2015 and 31 December 2025. Stroke was defined as a first-instance diagnosis of AIS, HS, or unspecified cerebrovascular event occurring within 24 h of ECMO cannulation during the index hospitalization. Propensity score matching (1:1 nearest neighbor) was performed to balance baseline demographics, comorbidities, anticoagulant use, and ECMO modality between the stroke and non-stroke cohorts. Primary outcomes included all-cause mortality at 30 days, 90 days, and 1 year. Secondary outcomes included cardiac arrest, seizures, palliative care utilization, and hospital readmission. Kaplan–Meier survival analysis and multivariable Cox proportional hazards modeling were performed. Results: Among 18,981 ECMO patients, 1481 (7.8%) developed a stroke within 24 h of ECMO cannulation, including 814 AIS (54.9%), 454 HS (30.6%), and 213 unspecified cerebrovascular events (14.4%). After propensity score matching, stroke was associated with significantly higher all-cause mortality at 30 days (RR 1.16), 90 days (RR 1.18), and 1 year (RR 1.18), all p < 0.05. Stroke was also associated with higher rates of cardiac arrest, seizures, hospital readmission, and palliative care utilization (all p < 0.001). AIS was associated with significantly lower mortality than HS at 30 days, 90 days, and 1 year (all p < 0.0001). In multivariable Cox regression, only HS was independently associated with increased 30-day mortality compared with no stroke. Markers of neurologic injury severity, including cerebral edema, brain compression, and coma, were among the strongest independent predictors of mortality. Conclusions: Stroke occurring early after ECMO cannulation is associated with substantially worse short- and long-term survival, with hemorrhagic subtype and markers of neurologic injury severity driving the strongest prognostic signals. These findings support early stroke recognition and subtype-informed prognostic discussions in ECMO patients. Full article
(This article belongs to the Special Issue Clinical Perspectives on Extracorporeal Membrane Oxygenation (ECMO))
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20 pages, 1632 KB  
Review
The Gut Microbiome in Heart Failure: Pathways to Inflammation and Therapeutic Targets
by Uday Sankar Akash Vankayala, Ali Sohail, Bivin George, Madhu Singh, Omar Khayat, Malek Kreidieh, Alia Hasham and Luis Quiel
Metabolites 2026, 16(6), 431; https://doi.org/10.3390/metabo16060431 (registering DOI) - 19 Jun 2026
Abstract
Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion [...] Read more.
Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article
(This article belongs to the Special Issue Metabolite Profiles in Inflammatory Diseases)
23 pages, 1079 KB  
Systematic Review
MRI-Based Radiomics and Artificial Intelligence for Prediction of Recurrence and Prognostic Outcomes in Oral Tongue Squamous Cell Carcinoma: A Systematic Review with Functional Meta-Synthesis
by Carlos M. Ardila, Eliana Pineda-Vélez, Anny M. Vivares-Builes and Alejandro I. Díaz-Laclaustra
Med. Sci. 2026, 14(2), 332; https://doi.org/10.3390/medsci14020332 (registering DOI) - 19 Jun 2026
Abstract
Background/Objectives: Oral tongue squamous cell carcinoma (OTSCC) remains clinically challenging because conventional clinicopathological markers do not fully explain variability in recurrence and survival. This systematic review and functional meta-synthesis aimed to identify and critically appraise studies using preoperative magnetic resonance imaging (MRI)-based radiomics, [...] Read more.
Background/Objectives: Oral tongue squamous cell carcinoma (OTSCC) remains clinically challenging because conventional clinicopathological markers do not fully explain variability in recurrence and survival. This systematic review and functional meta-synthesis aimed to identify and critically appraise studies using preoperative magnetic resonance imaging (MRI)-based radiomics, artificial intelligence (AI), deep learning, or quantitative MRI-derived models to predict recurrence and prognostic outcomes in OTSCC. Methods: PubMed, Scopus, and Embase were searched from inception to March 2026. Eligible studies included prognostic model investigations in adults with OTSCC or primary tongue cancer without reported base-of-tongue/oropharyngeal involvement, undergoing preoperative MRI and surgery, with recurrence- or survival-related follow-up. The primary synthesis was a functional meta-synthesis; pooling was not performed because studies were not sufficiently comparable. Results: Seven retrospective studies were included, with a summed descriptive sample of 1287 participants. The evidence base was heterogeneous in MRI sequences, segmentation workflows, model architecture, validation strategy, and endpoint definition. Functional meta-synthesis identified four domains: direct recurrence-oriented modeling, broader prognostic stratification, reported incremental or complementary value over clinical frameworks, and translational maturity/technical implementation. Several studies reported associations between MRI-derived signatures and recurrence- or survival-related outcomes, but findings were interpreted narratively because of differences in primary endpoints, imaging features, model design, validation methods, and outcome definitions. Most studies were judged at high overall risk of bias, and certainty of evidence ranged from low to very low. Conclusions: MRI-based radiomics and AI show preliminary promise for prognostic stratification in OTSCC, particularly recurrence-related risk refinement, but current evidence remains limited by retrospective design, heterogeneity, sparse external validation, and low certainty. Full article
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18 pages, 1553 KB  
Article
Preliminary Findings on the Predictive Value of Hematologic Inflammatory Indices for Survival in Treatment-Naïve Non-Metastatic Nasopharyngeal Carcinoma: A Retrospective Cohort Study
by Muhammed Ali Coşkuner, Gökhan Köker, Gizem Zorlu Görgülügil, Gülhan Özçelik Köker, Bilgin Bahadır Başgöz, Asım Armağan Aydın and Mustafa Yıldız
J. Clin. Med. 2026, 15(12), 4760; https://doi.org/10.3390/jcm15124760 (registering DOI) - 18 Jun 2026
Viewed by 41
Abstract
Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value [...] Read more.
Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value of pretreatment hematologic inflammatory indices for overall survival (OS) and progression-free survival (PFS) in patients with non-metastatic NPC. Methods: This single-center retrospective cohort study included adult patients with non-metastatic NPC diagnosed at a tertiary referral center between 20 February 2014 and 2 May 2023, with outcomes ascertained through 12 December 2023. Pretreatment complete blood count and biochemical parameters were used to calculate the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value (PIV), and hemoglobin–albumin–lymphocyte–platelet score. Receiver operating characteristic analysis determined optimal cut-off values for mortality discrimination. Associations with OS and PFS were assessed using Cox regression models. Results: Forty-six patients were analyzed, including 37 males. Median OS and PFS were 45.90 and 37.05 months, respectively. Compared with survivors, non-survivors were older and had lower hemoglobin and albumin levels, higher PIV, NLR, PLR, and SII values, and lower HALP scores. Although NLR showed the highest conventional ROC performance for mortality discrimination, PIV retained prognostic significance in multivariable Cox models and showed stable time-dependent discrimination for PFS. Conclusions: These preliminary findings suggest that pretreatment inflammatory indices, particularly composite markers such as PIV, may provide adjunctive prognostic information in treatment-naïve non-metastatic NPC, pending larger prospective validation. Full article
(This article belongs to the Section Oncology)
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25 pages, 464 KB  
Review
Biomarkers in Melanoma: Updates in Prognosis and Management
by Brett Crosby, Martin Guerra, Alyssa Crosby, Benjamin Linza, Kristel Lourdault and Richard Essner
Cancers 2026, 18(12), 1992; https://doi.org/10.3390/cancers18121992 - 18 Jun 2026
Viewed by 51
Abstract
Melanoma incidence rates have also been steadily increasing, emphasizing the need for improved prognostic and diagnostic tools with the goal of enhancing patients’ outcomes. Biomarkers in melanoma have emerged as an important component of melanoma management, offering insight into disease progression, tumor biology, [...] Read more.
Melanoma incidence rates have also been steadily increasing, emphasizing the need for improved prognostic and diagnostic tools with the goal of enhancing patients’ outcomes. Biomarkers in melanoma have emerged as an important component of melanoma management, offering insight into disease progression, tumor biology, and the potential for judging treatment responses. Traditionally, blood and immunohistochemical markers such as lactate dehydrogenase (LDH), S100 calcium-binding protein (S100B), human melanoma black-45 (HMB-45), and SRY-box transcription factor 10 (SOX10) have been widely used in melanoma diagnosis, staging, and monitoring. However, their clinical use has been limited because of their low specificity, especially in patients with early-stage disease. This has led to the development of molecular and genetic biomarkers, including BRAF, NRAS, and KIT mutations, which improved patients’ risk stratification and enabled targeted therapies, and gene expression signature assays such as DecisionDx (Castle Biosciences) and SkylineDx (Merlin) that are already used in clinics to help with surgical decisions and to assess patients’ prognosis. Other circulating biomarkers, including microRNAs, circulating tumor DNA and circulating tumor cells, have been developed to provide minimally invasive approaches to monitor tumor evolution and detect recurrence. However, none of these new approaches are used in clinics due to their low specificity and/or sensitivity. Additionally, nomograms or predictive models have been created using biomarkers and clinicopathologic data to assess patients’ outcomes and survival. While significant progress has been made, the integration of melanoma biomarkers into routine clinical practice remains limited. This review summarizes current advancements in melanoma biomarkers, including traditional serum and immunohistochemical markers, as well as developments in molecular, genetic, circulating, and predictive biomarker approaches. Full article
(This article belongs to the Special Issue The Latest Advancements in Cutaneous Melanoma)
18 pages, 992 KB  
Article
Prognostic Significance of Inflammatory Markers in Patients with Immune Thrombocytopenia
by Nur Oğuz Davutoğlu, Ali İhsan Gemici, Merve Kocaköse, Selçuk Uylaş, Şeyma Tanır, Gökhan Pektaş and Mehmet Bilgehan Pektaş
Int. J. Mol. Sci. 2026, 27(12), 5528; https://doi.org/10.3390/ijms27125528 (registering DOI) - 18 Jun 2026
Viewed by 44
Abstract
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory [...] Read more.
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
14 pages, 968 KB  
Article
Comparative Prognostic Performance of Nutritional and Inflammatory Indices in Diffuse Large B-Cell Lymphoma
by Tahir Alper Cinli, Gökhan Burul, Hasan Göze, Mesut Ayer and Istemi Serin
J. Clin. Med. 2026, 15(12), 4703; https://doi.org/10.3390/jcm15124703 - 17 Jun 2026
Viewed by 82
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma. Despite advances in immunochemotherapy, approximately 30–40% of patients experience relapsed or refractory disease. Nutritional and inflammatory status, reflected by composite indices, may independently influence clinical outcomes. However, the prognostic [...] Read more.
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma. Despite advances in immunochemotherapy, approximately 30–40% of patients experience relapsed or refractory disease. Nutritional and inflammatory status, reflected by composite indices, may independently influence clinical outcomes. However, the prognostic value of the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), and Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) score has not been well established in DLBCL patients treated with rituximab-based regimens. Methods: We retrospectively analyzed 192 patients with newly diagnosed DLBCL who received at least three cycles of R-CHOP or R-EPOCH at Başakşehir Çam and Sakura City Hospital between January 2020 and January 2026. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal cutoff values. Kaplan–Meier analysis with log-rank testing and univariable/multivariable Cox proportional hazards regression analyses were used to evaluate the prognostic impact of the PNI, GNRI, and HALP on overall survival (OS) and progression-free survival (PFS). Results: Among the six indices evaluated (PNI, GNRI, HALP, SII, ALI, and CAR), the PNI demonstrated the highest discriminatory ability for OS (AUC = 0.734, p = 0.001), followed by the HALP (AUC = 0.671, p = 0.020) and GNRI (AUC = 0.668, p = 0.022). The optimal cutoff values were ≤46.45 for the PNI, ≤46.91 for the GNRI, and ≤223.95 for HALP. Low values of all three indices were significantly associated with elevated LDH levels, advanced Ann Arbor stage, and higher IPI category. Kaplan–Meier analysis demonstrated significantly inferior OS in the low PNI (52.8 ± 2.6 vs. 67.1 ± 1.2 months, p = 0.001), low GNRI (49.5 ± 3.1 vs. 66.0 ± 1.4 months, p = 0.001), and low HALP (58.8 ± 2.8 vs. 64.9 ± 1.2 months, p = 0.005) groups. In separate multivariable Cox models adjusted for sex and IPI, the PNI (HR = 0.216, p = 0.009), HALP (HR = 0.276, p = 0.031), and GNRI (HR = 0.294, p = 0.011) remained independently associated with OS. No significant association was observed between these indices and PFS. Conclusions: The PNI, GNRI, and HALP are independent prognostic markers in patients with DLBCL treated with rituximab-based regimens. These readily available and inexpensive baseline indices may complement the IPI in identifying patients at higher risk of adverse outcomes and support risk stratification at diagnosis. Full article
(This article belongs to the Section Hematology)
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19 pages, 2417 KB  
Article
Serum β-hCG Combined with Traditional Tumor Markers Improves Detection Efficacy and Prognostic Prediction in Cholangiocarcinoma
by Suppakrit Kongsintaweesuk, Thatsanapong Pongking, Keerapach Tunbenjasiri, Pakornkiat Tanasuka, Sittiruk Roytrakul, Sudarat Onsurathum, Chawalit Pairojkul, Kitti Intuyod, Vor Luvira, Somchai Pinlaor, David Blair and Porntip Pinlaor
Int. J. Mol. Sci. 2026, 27(12), 5438; https://doi.org/10.3390/ijms27125438 - 16 Jun 2026
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Abstract
Cholangiocarcinoma (CCA) in Northeast Thailand is characterized by late diagnosis and poor prognosis, creating a critical need for effective early-detection biomarkers. This study utilized a multi-omics approach to identify novel diagnostic targets and improve CCA screening. Initial serum proteomic and transcriptomic analyses revealed [...] Read more.
Cholangiocarcinoma (CCA) in Northeast Thailand is characterized by late diagnosis and poor prognosis, creating a critical need for effective early-detection biomarkers. This study utilized a multi-omics approach to identify novel diagnostic targets and improve CCA screening. Initial serum proteomic and transcriptomic analyses revealed significant upregulation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in CCA patients, correlating with advanced disease stages. Interaction network analysis subsequently identified its circulating ligand, beta-human chorionic gonadotropin (β-hCG), as a highly translatable clinical target. The protein expression of β-hCG was assessed via immunohistochemistry (IHC) in 100 tissue samples, and serum levels of β-hCG, alongside routine markers (CA19-9, AFP, and CEA), were quantified in a cohort of 405 individuals, including 153 CCA patients. IHC confirmed significantly higher β-hCG expression in tumor tissues compared to adjacent areas (p < 0.0001). Serum β-hCG levels were significantly elevated in CCA patients and correlated with tumor volume and reduced overall survival. Diagnostically, a combined multiparameter panel (β-hCG, carbohydrate antigen 19-9, carcinoembryonic antigen, and alpha-fetoprotein) yielded excellent accuracy in distinguishing CCA from healthy controls (AUC: 0.962) and hepatocellular carcinoma cases (AUC: 0.890). However, discriminatory efficiency was notably lower when differentiating CCA from benign biliary diseases (AUC: 0.680) and liver metastases (AUC: 0.705). In conclusion, activation of the LHCGR signaling axis is a novel pathophysiological feature in CCA. When integrated into a multi-marker blood panel, circulating β-hCG serves as a valuable complementary risk-stratification and prognostic tool, though further optimization is required to overcome limited specificity in the presence of confounding liver pathologies before routine clinical implementation. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
14 pages, 1274 KB  
Article
Preoperative Pan-Immune-Inflammation Value for the Differential Diagnosis and Prognostic Assessment of Ovarian Tumors: A Retrospective Cohort Study
by Süleyman Özen and Muzaffer Sancı
Diagnostics 2026, 16(12), 1873; https://doi.org/10.3390/diagnostics16121873 - 16 Jun 2026
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Abstract
Background/Objectives: Preoperative differentiation of benign, borderline, and malignant ovarian tumors remains challenging. The pan-immune-inflammation value (PIV), a composite inflammation-based biomarker derived from routine blood counts, may contribute to ovarian tumor characterization. This study aimed to evaluate the diagnostic and prognostic significance of [...] Read more.
Background/Objectives: Preoperative differentiation of benign, borderline, and malignant ovarian tumors remains challenging. The pan-immune-inflammation value (PIV), a composite inflammation-based biomarker derived from routine blood counts, may contribute to ovarian tumor characterization. This study aimed to evaluate the diagnostic and prognostic significance of PIV in ovarian tumors. Methods: This retrospective single-center cohort study included 316 patients with histopathologically confirmed ovarian tumors classified as benign (n = 139), borderline (n = 61), or malignant (n = 116). Preoperative inflammatory indices were calculated from peripheral blood samples obtained within 24 h before surgery. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis and multivariable logistic regression. Progression-free survival (PFS) and overall survival (OS) were evaluated in malignant cases with available follow-up. Results: Inflammatory indices increased significantly from benign to borderline and malignant tumors (p < 0.001 for all). Among inflammatory markers, PIV demonstrated the highest diagnostic performance, with an area under the curve (AUC) of 0.852 (95% CI 0.808–0.893), sensitivity of 75.0%, and specificity of 80.5%. CA-125 demonstrated the highest overall diagnostic accuracy (AUC 0.978, 95% CI 0.961–0.991). Pairwise ROC analyses showed consistent discriminatory performance of PIV across ovarian tumor comparisons. In multivariable analysis, age, tumor size, ln(CA-125), and ln(PIV) were independently associated with malignancy (all p < 0.05). The combined CA-125 + PIV model demonstrated a statistically significant but modest improvement in diagnostic performance compared with CA-125 alone. During a median follow-up of 26.9 months (IQR 22.2–32.5), PIV was not significantly associated with PFS or OS. Conclusions: PIV demonstrated the highest diagnostic performance among evaluated inflammatory indices and may provide complementary information for preoperative epithelial ovarian tumor assessment. However, CA-125 remained the most accurate standalone biomarker, and the prognostic value of PIV appeared limited. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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11 pages, 473 KB  
Article
Prognostic Markers Associated with Short-Term Mortality in Dogs Hospitalised with Acute Pancreatitis: A Retrospective Study of 192 Cases
by Casandra Juárez Sarrión, Iván Rodríguez Armas, Ana Torrano Guillamón, Jorge Castro López and Carolina Arenas Bermejo
Animals 2026, 16(12), 1854; https://doi.org/10.3390/ani16121854 - 16 Jun 2026
Viewed by 146
Abstract
Objectives: To describe the clinical, clinicopathological and ultrasonographic characteristics of dogs with an acute pancreatitis (AP) and to identify prognostic markers associated with short-term mortality in a referral population. Methods: This retrospective observational study included 192 dogs hospitalised with AP at a referral [...] Read more.
Objectives: To describe the clinical, clinicopathological and ultrasonographic characteristics of dogs with an acute pancreatitis (AP) and to identify prognostic markers associated with short-term mortality in a referral population. Methods: This retrospective observational study included 192 dogs hospitalised with AP at a referral centre in Spain between 2021 and 2024. Dogs were classified as survivors or non-survivors based on survival to hospital discharge. Signalment, clinical findings, clinicopathological and ultrasonographic variables, comorbidities, treatments and duration of hospitalisation were recorded. Variables associated with outcome in univariable analyses were entered into a multivariable logistic regression model to identify independent predictors of death. Results: Of the 192 dogs, 141 (73.4%) survived and 51 (26.6%) died or were euthanised during hospitalisation. Non-survivors had higher serum creatinine, total bilirubin and alkaline phosphatase (ALKP) concentrations than survivors. In multivariable analysis, increased serum creatinine (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.32–4.11), total bilirubin (OR 1.42; 95% CI 1.03–2.06) and ALKP (OR 1.52; 95% CI 1.07–2.16) were independently associated with an increased risk of short-term mortality. Ultrasonographic abnormalities compatible with AP were identified in 121 dogs (63%), but were not independently associated with short-term mortality. Breed, age, sex, body weight, comorbidities and treatments were not associated with outcome. Clinical Significance: Measurement of serum creatinine, total bilirubin and ALKP concentrations at presentation may help identify dogs with AP at increased risk of death. Early recognition of high-risk patients may assist clinical decision-making, guide the intensity of monitoring, and facilitate communication with owners. Full article
(This article belongs to the Special Issue Advances in Companion Animal Gastroenterology)
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