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12 pages, 1077 KB  
Article
Nutritional Status Is Associated with Bone Mineral Density, Vitamin D Levels, and Bone Turnover Markers in Patients with Proximal Femoral Fragility Fractures: A Retrospective Observational Study
by Masahiro Iinuma, Takahiro Hideshima, Shinji Machida, Kenji Uehara, Tomoko Karube, Kentaro Sato and Naoki Haraguchi
Medicina 2026, 62(6), 1092; https://doi.org/10.3390/medicina62061092 - 4 Jun 2026
Viewed by 168
Abstract
Background and Objectives: Malnutrition is common among older adults with fragility fractures and is linked to poor clinical outcomes in orthopedic surgery. However, the association between nutritional status and bone-related parameters, including bone mineral density (BMD) and bone turnover markers, remains inadequately [...] Read more.
Background and Objectives: Malnutrition is common among older adults with fragility fractures and is linked to poor clinical outcomes in orthopedic surgery. However, the association between nutritional status and bone-related parameters, including bone mineral density (BMD) and bone turnover markers, remains inadequately characterized in this population. This study evaluated these associations in patients with proximal femoral fragility fractures. Materials and Methods: In total, 108 patients who underwent surgery for proximal femoral fragility fractures were retrospectively analyzed. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) score. BMD was measured at the femoral neck of the proximal femur and the lumbar spine using dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D (25[OH]D) and bone turnover markers, including total procollagen type I N-terminal propeptide and tartrate-resistant acid phosphatase 5b, were also evaluated. Correlation analyses, group comparisons, and multivariate linear regression analysis were performed to identify factors independently associated with femoral neck BMD. Results: GNRI and PNI were significantly positively correlated with femoral neck BMD (r = 0.48 and r = 0.26, respectively; both p < 0.01), while the CONUT score showed a significant negative correlation (r = −0.27, p < 0.01). Nutritional indices were not significantly correlated with lumbar spine BMD. Patients classified as malnourished by GNRI or PNI had significantly lower femoral neck BMD and serum 25(OH)D and higher bone turnover markers than well-nourished patients. Multivariate linear regression analysis revealed that GNRI, PNI, and CONUT score remained independently associated with femoral neck BMD after adjusting for age, sex, and body mass index. Conclusions: Nutritional status assessed by hematological indices was significantly associated with femoral neck BMD and bone metabolism markers in patients with proximal femoral fragility fractures. Findings underscore the importance of nutritional status in bone health and should be considered in the management of osteoporosis and fragility fractures. Full article
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9 pages, 292 KB  
Article
Serum Epithelial Biomarkers and Oxidative Stress Indicators in Acute Bronchiolitis: Association with Disease Severity and Recurrent Wheezing
by Yeşim Yiğit, Özge Yılmaz, Ece Onur, Yurda Şimşek, Arzu Oran, Esra Toprak Kanık and Hasan Yüksel
Children 2026, 13(6), 768; https://doi.org/10.3390/children13060768 - 1 Jun 2026
Viewed by 162
Abstract
Background: Acute bronchiolitis is one of the most common lower respiratory tract infections in early childhood and is frequently associated with recurrent wheezing and later development of asthma. Identifying biomarkers related to airway epithelial injury and disease severity may improve risk stratification. Materials [...] Read more.
Background: Acute bronchiolitis is one of the most common lower respiratory tract infections in early childhood and is frequently associated with recurrent wheezing and later development of asthma. Identifying biomarkers related to airway epithelial injury and disease severity may improve risk stratification. Materials and Methods: A total of 155 children aged 1–36 months who presented with their first episode of wheezing were enrolled. Clinical data and bronchiolitis symptom scores were recorded at admission. Serum levels of CC16, surfactant protein-D (SP-D), YKL-40, and isoprostane were measured. Patients were followed for one year to assess recurrence of wheezing. Results: According to symptom scores, 81 patients had mild and 74 had moderate bronchiolitis; no severe cases were observed. The distribution of bronchiolitis severity differed significantly between recurrent and non-recurrent wheezing groups. Serum YKL-40 levels were significantly correlated with disease severity (p < 0.05), and the effect size analysis indicated a moderate effect. SP-D levels showed a non-significant trend with severity (p = 0.17). No significant associations were observed for CC16 or isoprostane. Conclusions: Serum YKL-40 may be a potential biomarker reflecting disease severity in children with acute bronchiolitis. Further longitudinal studies are needed to evaluate the prognostic value of epithelial injury markers for recurrent wheezing and asthma development. Full article
(This article belongs to the Section Pediatric Pulmonary and Sleep Medicine)
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11 pages, 1413 KB  
Article
Serum Creatinine Level at One Month Post-Transplant Predicts 3-Year and 5-Year Graft Survival and Renal Function: A Large Single-Center Retrospective Cohort Study
by Jungjun Lee, Sunyoung Son and Manki Ju
J. Clin. Med. 2026, 15(11), 4238; https://doi.org/10.3390/jcm15114238 - 30 May 2026
Viewed by 172
Abstract
Background: Contemporary kidney transplantation increasingly includes high-immunologic-risk recipients, ABO-incompatible transplantation, deceased-donor transplantation, and desensitization protocols. Although early post-transplant serum creatinine has historically been associated with long-term graft outcomes, its prognostic value in modern high-risk transplant cohorts remains insufficiently characterized. We evaluated whether [...] Read more.
Background: Contemporary kidney transplantation increasingly includes high-immunologic-risk recipients, ABO-incompatible transplantation, deceased-donor transplantation, and desensitization protocols. Although early post-transplant serum creatinine has historically been associated with long-term graft outcomes, its prognostic value in modern high-risk transplant cohorts remains insufficiently characterized. We evaluated whether serum creatinine at one month post-transplant independently predicts 3-year and 5-year graft survival and renal function in a large contemporary kidney transplant cohort. Methods: Among 1895 consecutive KT recipients (2005–2018), patients were stratified by one-month serum creatinine into four quartiles: Q1 (<1.0 mg/dL, n = 398), Q2 (1.0–1.23, n = 480), Q3 (1.23–1.52, n = 487), and Q4 (≥1.52, n = 530). Primary endpoints were 3- and 5-year death-censored graft survival. Results: Median follow-up was 95 months. Three-year graft survival was 97.2%, 96.2%, 95.3%, and 90.3% for Q1–Q4, respectively; 5-year survival was 94.5%, 94.6%, 92.5%, and 86.9%. eGFR stratification persisted at both 3 and 5 years. After adjustment including donor and recipient BMI, Q4 creatinine independently predicted graft failure (HR, 1.590; 95% CI, 1.049–2.412; p = 0.029). One-month serum creatinine also remained significant as a continuous variable (HR, 1.409 per 1.0 mg/dL increase; 95% CI, 1.279–1.551; p < 0.001). ROC analysis identified an optimal cutoff of 1.39 mg/dL (AUC, 0.622; sensitivity, 52.6%; specificity, 65.0%). Conclusions: One-month serum creatinine is a robust and independent predictor of graft survival and renal function after kidney transplantation. These findings support its use as a simple early risk-stratification marker and as a trigger for targeted post-transplant surveillance. Full article
(This article belongs to the Special Issue The Latest Advancements in Solid Organ Transplantation)
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19 pages, 4217 KB  
Article
Comparison of Methods for the Isolation of Salivary Extracellular Vesicles
by Ulrike Kegler, Anja Buhmann, Heinz-Peter Friedl, Manuela Hofner and Christa Noehammer
Int. J. Mol. Sci. 2026, 27(11), 4899; https://doi.org/10.3390/ijms27114899 - 28 May 2026
Viewed by 165
Abstract
Extracellular vesicles (EVs) have attracted growing attention for their diagnostic and prognostic potential as they carry molecular cargo such as DNA, RNA, proteins and lipids derived from their cells of origin. While EV research has traditionally focused on blood, this study explicitly explored [...] Read more.
Extracellular vesicles (EVs) have attracted growing attention for their diagnostic and prognostic potential as they carry molecular cargo such as DNA, RNA, proteins and lipids derived from their cells of origin. While EV research has traditionally focused on blood, this study explicitly explored saliva as a promising, non-invasive sample matrix for EV isolation and biomarker discovery. Six different EV isolation methods were compared for their ability to recover salivary small EVs suitable for downstream DNA and microRNA analysis. Nanoparticle tracking analysis (NTA) revealed variation in vesicle sizes, concentrations and surface charges across all tested EV isolation approaches. In addition to being the fastest and simplest isolation method, the miRCURY Exosome Isolation kit—serum and plasma from Qiagen (ExiQ) also resulted in the highest EV yields with average particle sizes of ~130 nm. Western blot analysis further verified the presence of EV-specific markers (CD9, Alix) and no detectable signal for ApoA1 as an indicator for lipoprotein contamination, underscoring the purity of ExiQ-isolated vesicles. Always applying the same protocol for parallel DNA and RNA isolation on vesicles extracted by various methods, differences in DNA and RNA yields were observed across the evaluated isolation kits. ExiQ-isolated EVs showed the best recovery for both nucleic acid types. Notably, nuclease treatment of isolated EVs revealed that substantial amounts of DNA were present on the EV surface, whereas microRNA was predominantly localized within the vesicles. The present study, extensively comparing different EV isolation methods, demonstrates that salivary EVs are a viable source for non-invasive diagnostics and suggests the miRCURY Exosome Isolation kit—serum and plasma from Qiagen (ExiQ) to be a good choice for integration in future salivary EV-based diagnostic assays given its simplicity, speed and excellent performance. Full article
(This article belongs to the Special Issue Extracellular Vesicles—New Findings on the Block in Liquid Biopsy)
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18 pages, 1007 KB  
Article
Detection of Exostosin 1 in Lupus Nephritis: Prevalence, Clinico–Pathologic and Renal Outcome Correlations
by Luiza Liza de Assis, Denise Maria Avancini Costa Malheiros, Dirce Maria Zanetta and Luis Yu
Diagnostics 2026, 16(11), 1591; https://doi.org/10.3390/diagnostics16111591 - 23 May 2026
Viewed by 438
Abstract
Background/Objectives: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE); it is associated with increased morbidity and mortality, underscoring the need for new diagnostic markers and therapeutic strategies. In this context, the exostosin 1 (EXT1)/exostosin 2 [...] Read more.
Background/Objectives: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE); it is associated with increased morbidity and mortality, underscoring the need for new diagnostic markers and therapeutic strategies. In this context, the exostosin 1 (EXT1)/exostosin 2 (EXT2) heterodimer has emerged as a novel antigen in membranous nephropathy associated with SLE. This study evaluated EXT1 prevalence in renal biopsies from patients with lupus membranous nephropathy (LMN) and compared clinical, laboratory, and histopathological characteristics on diagnosis and renal outcomes. Methods: This retrospective study included 97 LMN patients whose renal biopsy underwent immunohistochemistry (IHC) for EXT1. EXT1-positive and EXT1-negative groups were compared using descriptive analyses and repeated measures models. Results: EXT1 positivity was observed in 35% of the cohort, and is more frequent in pure LMN (40%) than in cases with a proliferative component (32%). Regarding SLE diagnostic criteria, EXT1-positive patients showed a higher frequency of antiphospholipid antibodies, although data were available for only a subset of patients. This group also exhibited lower serum creatinine levels, but without statistical significance. EXT1-negative patients more frequently received cyclophosphamide as induction therapy (57.6% vs. 34.5%; p = 0.041). No differences in clinical outcomes were observed during follow-up. Conclusions: EXT1 prevalence was consistent with the literature, reinforcing the epidemiological reproducibility of this marker. EXT1-positive and EXT1-negative groups did not differ regarding clinical presentation, disease progression, and renal outcomes, heightening the need for prospective studies to further elucidate the diagnostic and prognostic role of EXT1 in LMN. Full article
(This article belongs to the Special Issue Current Issues in Kidney Diseases Diagnosis and Management 2026)
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21 pages, 10662 KB  
Article
Pathogenic Mutations in the Tumor Microenvironment Drive Tumor Progression in Diffuse Large B-Cell Lymphoma Through Tumor–Stroma Cross-Talk
by Vaishali Aggarwal, Radhika Srinivasan, Amanjit Bal, Pankaj Malhotra, Subhash Varma and Ashim Das
Cancers 2026, 18(11), 1697; https://doi.org/10.3390/cancers18111697 - 22 May 2026
Viewed by 272
Abstract
Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the [...] Read more.
Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-β, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor–stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL. Full article
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21 pages, 1076 KB  
Review
Alpha-Fetoprotein as a Biomarker in Pregnancy: From Genetic Disorders to Obstetric Complications
by Shaqraa Musawi
Curr. Issues Mol. Biol. 2026, 48(5), 534; https://doi.org/10.3390/cimb48050534 - 20 May 2026
Viewed by 230
Abstract
Alpha-fetoprotein (AFP) is a glycoprotein primarily produced by the fetal liver and yolk sac during development. It is a multifaceted biomarker with significant applications in the prenatal screening of congenital abnormalities, cancer, and other disorders. The level of AFP in maternal blood may [...] Read more.
Alpha-fetoprotein (AFP) is a glycoprotein primarily produced by the fetal liver and yolk sac during development. It is a multifaceted biomarker with significant applications in the prenatal screening of congenital abnormalities, cancer, and other disorders. The level of AFP in maternal blood may indicate several obstetric concerns and complications during pregnancy. Atypical AFP levels are commonly utilized as a biomarker for detecting fetal anomalies, placental complications, and other pregnancy-related issues. These findings raise concerns regarding the effectiveness of screening maternal serum alpha-fetoprotein (MS-AFP) as a primary indicator of pregnancy problems and underscore the need for further investigation into the functional role of AFP throughout pregnancy. The measurement of MS-AFP has been utilized for the past four decades. It is anticipated that MS-AFP measurement will continue to be utilized as a component of integrated or sequential tests for chromosomal abnormalities and may serve as a prognostic indicator for adverse obstetric outcomes. Critically, whether AFP functions solely as a passive marker or plays active biological roles in pregnancy physiology and pathology remains unresolved, necessitating additional mechanistic investigation and discourse. This review consolidates critical data from numerous studies on AFP, focusing specifically on its diagnostic and prognostic applications for congenital abnormalities and problems during pregnancy. This review also identifies key research gaps regarding the functional biology of AFP, particularly whether AFP functions as a passive biomarker or an active participant in the pathophysiology of adverse pregnancy outcomes. Full article
(This article belongs to the Special Issue Targeted Therapies and Biomarker Discovery in Health and Disease)
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15 pages, 1413 KB  
Article
Nephrinuria as an Early Biomarker of Renal Injury in Hypertensive Patients After COVID-19: A Comparative Study
by Gulomjon Kholov, Nilufar Akhmedova, Ulugbek Ochilov, Sukhrob Nurulloyev, Sitora Mukhammadiyeva, Nozima Djuraeva, Otabek Fayzulloyev, Abdugappor Insopov, Sanobar Rakhmonova, Mehriniso Ochilova, Rajab Bobokalonov, Akmal Djumaev, Zulfiya Abulova, Dildora Otajonova, Mokhibegim Nematova, Nigina Shukurova, Navbakhor Nazarova, Dildora Komilova, Mehinbonu Nurmukhammedova and Dilfuza Rakhmonova
COVID 2026, 6(5), 87; https://doi.org/10.3390/covid6050087 - 20 May 2026
Viewed by 342
Abstract
Background: Hypertension is one of the most prevalent comorbidities in patients with COVID-19 and a major contributor to chronic kidney disease (CKD). Traditional kidney injury markers, including creatinine, estimated glomerular filtration rate (eGFR) and microalbuminuria, reflect renal injury only after substantial nephron loss [...] Read more.
Background: Hypertension is one of the most prevalent comorbidities in patients with COVID-19 and a major contributor to chronic kidney disease (CKD). Traditional kidney injury markers, including creatinine, estimated glomerular filtration rate (eGFR) and microalbuminuria, reflect renal injury only after substantial nephron loss has already occurred. Urinary podocyte proteins, such as nephrin (nephrinuria), have been suggested as early markers of glomerular barrier dysfunction; however, their clinical behavior and diagnostic value in hypertensive patients with previous SARS-CoV-2 infection are unknown. Aim: To assess urinary nephrinuria, microalbuminuria, transforming growth factor β1 (TGF-β1), aldosterone, vascular endothelial growth factor A (VEGF-A) and renal hemodynamics across different stages of hypertension in patients with and without a history of COVID-19 and to assess the response to conventional antihypertensive and nephroprotective treatment. Methods: In a prospective comparative cohort study, 120 patients (aged 30–60 years) with stage I–III essential hypertension were stratified by COVID-19 history into a post-COVID-19 group (n = 60) and a non-COVID-19 group (n = 60); within each group, 20 patients were assigned to each hypertension stage. Comparisons were performed between the post-COVID-19 and non-COVID-19 subgroups at the same hypertension stage. Serum creatinine, cystatin-C, aldosterone, TGF-β1 and VEGF-A, urinary microalbumin and nephrin and intrarenal Doppler hemodynamics were measured at baseline and after six months of guideline-based treatment. Results: Nephrinuria was markedly increased in post-COVID-19 patients in all stages of hypertension, including stage I, where serum creatinine, cystatin-C and eGFR were within the normal range (126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01). Nephrinuria was strongly correlated with renal functional reserve (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001), microalbuminuria (r = 0.758, p < 0.001), aldosterone (r = 0.613, p < 0.001) and VEGF-A (r = 0.589, p < 0.001). Antihypertensive and nephroprotective treatment for six months decreased nephrinuria, blood pressure and TGF-β1, with more limited effects in stage III disease. Conclusions: Nephrinuria was found to be an early marker of renal involvement in COVID-19, occurring before microalbuminuria and conventional functional markers and with a greater relative difference than these markers in stage I disease, suggesting podocyte injury as an early and potentially reversible mechanism of post-COVID renal involvement in hypertensive patients. Nephrinuria seems to be a potential biomarker for early renal surveillance in this population and its prognostic role for incident CKD needs to be validated in longitudinal outcome studies. Full article
(This article belongs to the Special Issue Long COVID: Pathophysiology, Symptoms, Treatment, and Management)
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11 pages, 799 KB  
Article
Diagnostic Performance and Prognostic Value of Serum Amyloid A in Patients with Bloodstream Infection
by Hyein Kang and Sunggyun Park
Diagnostics 2026, 16(10), 1510; https://doi.org/10.3390/diagnostics16101510 - 16 May 2026
Viewed by 304
Abstract
Background: Serum amyloid A (SAA) is an acute-phase reactant that increases rapidly in response to inflammatory stimuli and infection, earlier and more markedly than conventional markers such as C-reactive protein (CRP). However, large-scale evidence of its clinical utility in bloodstream infections (BSIs) remains [...] Read more.
Background: Serum amyloid A (SAA) is an acute-phase reactant that increases rapidly in response to inflammatory stimuli and infection, earlier and more markedly than conventional markers such as C-reactive protein (CRP). However, large-scale evidence of its clinical utility in bloodstream infections (BSIs) remains limited. This study aimed to evaluate the diagnostic and prognostic value of SAA in patients presenting to the emergency department (ED) with suspected infection. Methods: We retrospectively reviewed the electronic medical records of adult patients who underwent simultaneous SAA and blood culture (BC) testing at the ED of a tertiary referral hospital between January and December 2025. Initial laboratory data, including CRP, procalcitonin (PCT), white blood cell (WBC) count, and absolute neutrophil count (ANC), were collected, and BSI was defined as the isolation of pathogenic organisms in BC. Correlations and agreement between SAA and other markers were assessed, and the diagnostic performance of BSI was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Survival outcomes were analyzed using the Kaplan–Meier method. Results: Among the 3321 included patients, 379 patients (11.4%) had positive BCs. Median SAA levels were significantly higher in BSI patients than in non-BSI patients (202.0 vs. 71.0 mg/L, p < 0.001), with the highest levels observed in Gram-negative infections. SAA showed a strong correlation with CRP (rs = 0.884) and a moderate correlation with PCT (rs = 0.576). The AUC for BSI diagnosis was highest for PCT (0.789), followed by SAA (0.650). The SAA demonstrated high sensitivity (90.5%) but low specificity (26.9%). Higher SAA levels were significantly associated with increased mortality rates. Conclusions: In adult ED patients, SAA is significantly associated with BSI and mortality and is a sensitive biomarker for the early detection of BSIs. Although SAA alone showed inferior discriminative performance compared to PCT, it may serve as an adjunctive screening tool in the ED, particularly in settings where PCT availability is limited. Full article
(This article belongs to the Special Issue Biochemical Testing Applications in Clinical Diagnosis—2nd Edition)
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20 pages, 691 KB  
Review
Circulating Cytokines in Melanoma Prognosis: Current Evidence and Future Perspectives
by Ignas Lapeikis and Vincas Urbonas
Medicina 2026, 62(5), 960; https://doi.org/10.3390/medicina62050960 - 14 May 2026
Viewed by 471
Abstract
Cutaneous melanoma remains a highly lethal malignancy once metastatic. Current prognostic stratification relies primarily on staging and serum lactate dehydrogenase (LDH), which incompletely captures inter-patient biological heterogeneity. Increasing evidence highlights the importance of tumour–immune interactions in melanoma progression and response to therapy. This [...] Read more.
Cutaneous melanoma remains a highly lethal malignancy once metastatic. Current prognostic stratification relies primarily on staging and serum lactate dehydrogenase (LDH), which incompletely captures inter-patient biological heterogeneity. Increasing evidence highlights the importance of tumour–immune interactions in melanoma progression and response to therapy. This narrative review summarises and critically evaluates current evidence on circulating cytokines as prognostic and biologically informative biomarkers in melanoma, with particular emphasis on the immunotherapy era. Several circulating cytokines—most consistently interleukin-6 (IL-6) and interleukin-8 (IL-8)—are associated with adverse outcomes in advanced melanoma. However, baseline elevations predominantly reflect tumour burden and systemic inflammation, indicating prognostic rather than treatment-specific predictive value. In contrast, early on-treatment changes, particularly decreases in IL-8, may better capture evolving tumour–immune interactions during immune checkpoint inhibitor therapy. C-reactive protein (CRP), a downstream marker of IL-6 signalling, similarly reflects systemic inflammatory status and carries reproducible prognostic significance. Early circulating tumour DNA (ctDNA) dynamics demonstrate strong associations with response and survival and may provide complementary insight into tumour burden kinetics. Conversely, cytokines central to effective antitumour immunity, such as interferon-γ (IFN-γ), are more reliably characterised at the tumour transcriptional level than by circulating protein measurements. Circulating cytokines represent biologically meaningful but methodologically challenging biomarkers in melanoma. Their most realistic clinical role lies in complementing established prognostic factors within integrated biomarker frameworks rather than functioning as standalone tests. Standardisation of pre-analytical handling, assay platforms, and sampling time points, together with prospective validation, is essential before broader clinical implementation. Full article
(This article belongs to the Special Issue Novel Challenges and Personalized Treatment of Melanoma)
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19 pages, 1961 KB  
Article
Prognostic Impact of Baseline Albumin–Bilirubin Score on Mortality After Transcatheter Edge-to-Edge Mitral Repair
by Ümeyir Savur, Berhan Keskin, Aysel Akhundova, Aykun Hakgor, Haci Murat Güneş and Bilal Boztosun
Medicina 2026, 62(5), 944; https://doi.org/10.3390/medicina62050944 - 12 May 2026
Viewed by 307
Abstract
Background and Objectives: Transcatheter edge-to-edge repair (TEER) has emerged as an effective treatment option for patients with severe mitral regurgitation who are at high surgical risk. However, clinical outcomes after TEER remain heterogeneous and are influenced not only by cardiac parameters but [...] Read more.
Background and Objectives: Transcatheter edge-to-edge repair (TEER) has emerged as an effective treatment option for patients with severe mitral regurgitation who are at high surgical risk. However, clinical outcomes after TEER remain heterogeneous and are influenced not only by cardiac parameters but also by systemic comorbidities and multiorgan dysfunction. The albumin–bilirubin (ALBI) score, derived from serum albumin and bilirubin levels, has recently been proposed as a simple marker of hepatic dysfunction and cardio-hepatic interaction. This study aimed to evaluate the prognostic value of baseline ALBI score in predicting long-term mortality after TEER. Materials and Methods: In this single-center retrospective cohort study, 106 consecutive patients with symptomatic moderate-to-severe or severe mitral regurgitation who underwent TEER between January 2019 and December 2025 were included. Baseline ALBI score was calculated using pre-procedural serum albumin and bilirubin levels. Cox proportional hazards regression analysis was used to identify predictors of long-term mortality. Variable selection was performed using least absolute shrinkage and selection operator (LASSO) regression, followed by ridge-penalized multivariable Cox modeling to minimize overfitting. The incremental prognostic value of ALBI was assessed using concordance index (C-index) comparison between predictive models. Receiver operating characteristic (ROC) analysis and Kaplan–Meier survival analysis were also performed. Results: During a median follow-up of 17.9 months, 30 patients (28.3%) died. Higher baseline ALBI scores were significantly associated with increased mortality risk. In multivariable analysis, ALBI score (HR 3.35, 95% CI 1.46–7.71; p = 0.004), left atrial volume index (LAVI) (HR 1.02, 95% CI 1.01–1.03; p = 0.005), and log-transformed B-type natriuretic peptide (BNP) (HR 1.37, 95% CI 1.02–1.86; p = 0.039) remained independent predictors of mortality. Addition of the ALBI score improved model discrimination, increasing the C-index from 0.845 to 0.886. ROC analysis demonstrated good predictive performance of the ALBI score (area under the curve [AUC] = 0.877), with an optimal cut-off value of −1.67. Conclusions: Baseline ALBI score is independently associated with long-term mortality after TEER and may provide potential incremental prognostic information. However, the observed improvement is modest and should be interpreted cautiously. These findings support a potential role of ALBI as a complementary marker, which requires validation in larger prospective studies. Full article
(This article belongs to the Section Cardiology)
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16 pages, 1998 KB  
Article
GPIHBP1 as a Biomarker of Diabetic Polyneuropathy and Vascular Complications in Type 2 Diabetes Mellitus
by Savelia Yordanova, Antoaneta Gateva, Diana Nikolova, Julieta Hristova and Zdravko Kamenov
Biomolecules 2026, 16(5), 707; https://doi.org/10.3390/biom16050707 - 11 May 2026
Viewed by 454
Abstract
Background: Diabetic neuropathy is one of the most common chronic complications of diabetes mellitus and could lead to foot ulcerations, lower-limb amputations, increased mortality and reduced quality of life. This study examines the level of GPIHBP1 to assess its diagnostic and prognostic values [...] Read more.
Background: Diabetic neuropathy is one of the most common chronic complications of diabetes mellitus and could lead to foot ulcerations, lower-limb amputations, increased mortality and reduced quality of life. This study examines the level of GPIHBP1 to assess its diagnostic and prognostic values across the metabolic continuum. Methods: This is an observational monocentric study, including 160 patients with type 2 diabetes mellitus, obesity without carbohydrate metabolism disorders and healthy controls. Clinical data and laboratory results were collected, and serum levels of GPIHBP1 were measured using an ELISA. The presence of DPN for the diabetes group was assessed using corneal confocal microscopy and NDS. The statistical analyses included t-tests, Pearson’s correlation analysis, and ROC analysis to explore associations and the predictive values of the biomarker. Results: The GPIHBP1 levels increased progressively, with the lowest levels observed in the control group, higher levels in patients with obesity, and the highest levels in those with diabetes mellitus. Higher GPIHBP1 levels were observed in patients with peripheral diabetic neuropathy compared to those without. GPIHBP1 demonstrated moderate discriminative performance for the presence of diabetes, diabetic neuropathy and nephropathy. GPIHBP1 levels were also associated with renal function parameters and markers of vascular involvement. After adjustment for confounders, including estimated glomerular filtration rate (eGFR), the association between GPIHBP1 and diabetic neuropathy remained statistically significant although attenuated. Higher levels were observed in patients with coronary artery disease, and a positive correlation was established with mean IMT and sudomotor dysfunction score. Conclusions: Circulating GPIHBP1 levels are associated with diabetes mellitus and its micro- and macrovascular complications, particularly diabetic neuropathy. Its measurement could enhance early diagnosis and personalized management of T2DM, and, while these findings support a potential role of GPIHBP1 as a biomarker of metabolic and vascular dysfunction, its clinical utility requires confirmation in longitudinal studies. Full article
(This article belongs to the Section Molecular Biomarkers)
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29 pages, 13068 KB  
Article
A Unified Histopathological Framework of Liver Fibrogenesis in Chronic Viral Hepatitis B, C and Coinfection
by Alina Dumitrache (Păunescu), Nicoleta Anca Ionescu (Șuțan), Liliana Cristina Soare, Maria Cristina Ponepal, Ana Cătălina Țânțu, Monica Marilena Țânțu, Ileana Monica Baniță and Cătălina Gabriela Pisoschi
Diseases 2026, 14(5), 165; https://doi.org/10.3390/diseases14050165 - 8 May 2026
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Abstract
Background: Chronic hepatitis B and C remain major causes of progressive liver disease, while HBV–HCV coinfection is associated with accelerated fibrosis and hepatocellular injury. Methods: This study evaluated integrated biochemical, histopathological, and immunohistochemical features in patients with chronic hepatitis B (CHB, n = [...] Read more.
Background: Chronic hepatitis B and C remain major causes of progressive liver disease, while HBV–HCV coinfection is associated with accelerated fibrosis and hepatocellular injury. Methods: This study evaluated integrated biochemical, histopathological, and immunohistochemical features in patients with chronic hepatitis B (CHB, n = 29), chronic hepatitis C (CHC, n = 15), and CHB+C coinfection (CHB+C, n = 10). Liver biopsies were assessed using Ishak and METAVIR scoring systems, alongside immunohistochemical analysis of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), CD5L, and glial fibrillary acidic protein (GFAP), quantified by H-score. These findings were correlated with biochemical, hematological, and prognostic parameters. Results: Coinfected patients exhibited significantly higher serum ALT, AST, and GGT levels (p ≤ 0.011) and increased CD5L expression (median H-score 197.5 vs. 135 in CHB, p = 0.009), indicating enhanced macrophage-associated inflammatory activity. Although fibrosis stages were comparable across groups, median H-scores for α-SMA, TGF-β1, and GFAP showed a consistent upward trend in CHB+C, suggesting intensified profibrogenic signaling. Principal Component Analysis identified distinct biochemical clusters related to hepatocellular injury, hepatic functional impairment (synthetic and excretory axis), and lipid metabolism. Conclusions: These findings highlight a multidimensional pattern of liver injury in chronic viral hepatitis, with CHB+C coinfection amplifying profibrogenic and hepatocellular markers, both biochemically and histologically. Full article
(This article belongs to the Special Issue Viral Hepatitis: Diagnosis, Treatment and Management—2nd Edition)
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13 pages, 460 KB  
Article
Admission Electrolyte Abnormalities and Clinical Outcomes in Hospitalized COVID-19 Patients
by Emine Önder, Aysun Ekinci, Fırat Aşır, Cigdem Mermutluoglu, Erdal Ozbek, Pakize Gamze Erten Bucaktepe and Ismail Yildiz
Medicina 2026, 62(5), 913; https://doi.org/10.3390/medicina62050913 - 8 May 2026
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Abstract
Background and Objectives: Electrolyte abnormalities are frequently observed in hospitalized patients with acute infections and may reflect underlying disease severity. This study aimed to investigate the association between baseline electrolyte disturbances and clinical outcomes in patients with COVID-19, with a particular focus on [...] Read more.
Background and Objectives: Electrolyte abnormalities are frequently observed in hospitalized patients with acute infections and may reflect underlying disease severity. This study aimed to investigate the association between baseline electrolyte disturbances and clinical outcomes in patients with COVID-19, with a particular focus on albumin-corrected calcium levels. Materials and Methods: This retrospective study included 348 hospitalized patients with COVID-19. Primary analyses were restricted to RT-PCR-confirmed cases (n = 272) to minimize misclassification bias, while the full cohort was evaluated in sensitivity analyses. Baseline electrolyte levels at admission were recorded, and corrected calcium levels were calculated using serum albumin. Clinical outcomes included prolonged hospitalization (defined relative to the cohort median), intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital mortality. Multivariable logistic regression analyses were performed adjusting for age, sex, and renal function (eGFR). Results: In the PCR-confirmed cohort, corrected hypocalcemia was present in 37.3% of patients. In univariate analyses, hypocalcemia, hyponatremia, and hypophosphatemia were significantly associated with adverse outcomes. However, after adjustment, corrected hypocalcemia did not retain independent significance. Hyponatremia remained independently associated with ICU admission (OR: 9.45, 95% CI: 2.12–42.1, p = 0.003), while hypophosphatemia was independently associated with prolonged hospitalization (OR: 2.83, 95% CI: 1.36–5.91, p = 0.005). No electrolyte abnormality demonstrated a stable independent association with IMV requirement or mortality after adjustment. Sensitivity analyses in the full cohort yielded consistent findings. Conclusions: Electrolyte abnormalities are common in hospitalized COVID-19 patients and are associated with worse clinical outcomes; however, they primarily reflect overall disease severity rather than acting as independent prognostic determinants. Routine electrolyte measurements may provide accessible and clinically informative markers but should be interpreted in conjunction with other clinical parameters. Full article
(This article belongs to the Special Issue Emerging Trends in Infectious Disease Prevention and Control)
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14 pages, 749 KB  
Article
Serum Calprotectin Concentration in Patients with Oral Lichen Planus: A Cross-Sectional Study
by Ana Glavina, Helena Erić, Daniela Šupe-Domić and Antonija Tadin
Medicina 2026, 62(5), 891; https://doi.org/10.3390/medicina62050891 - 6 May 2026
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Abstract
Background and Objectives: Oral lichen planus (OLP) is a mucocutaneous autoimmune disease with a complex aetiology and an entirely unknown pathophysiological mechanism. Calprotectin (CP) is an inflammation-related protein and a potential biomarker of disease activity. This study aimed to examine the association [...] Read more.
Background and Objectives: Oral lichen planus (OLP) is a mucocutaneous autoimmune disease with a complex aetiology and an entirely unknown pathophysiological mechanism. Calprotectin (CP) is an inflammation-related protein and a potential biomarker of disease activity. This study aimed to examine the association between serum calprotectin (sCP), disease duration, and disease activity in patients with erosive (active) and non-erosive (inactive) OLP. Materials and Methods: This cross-sectional study included 50 participants: 30 patients with OLP (20 erosive, 10 non-erosive) and 20 healthy controls. Medical and dental histories, sociodemographic data, disease duration, and OLP activity assessed by the Oral Lichen Planus Disease Activity Scale (OLP-DAS) were recorded, along with inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and sCP]. Results: Non-erosive OLP patients had a statistically significantly higher sCP concentration than erosive patients (2.32 μg/mL vs. 1.34 μg/mL, p = 0.018). The area under the curve (AUC) was 43.9% in OLP patients (p = 0.470). There were no statistically significant differences between OLP patients and controls for ESR (p = 0.878), CRP (p = 0.439), or LDH (p = 0.476). There was a weak negative correlation between sCP concentration and disease duration in erosive (r1 = −0.115, p1 = 0.629) and non-erosive OLP (r2 = −0.166, p2 = 0.647). There was a moderate, negative, statistically significant correlation between sCP concentration and OLP-DAS (r = −0.455, p = 0.012). Conclusions: The findings of this study indicate that OLP inflammation is primarily local and chronic, rather than systemic. Serum CP showed limited diagnostic and prognostic value. Full article
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