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10 pages, 922 KB  
Article
Development of a Novel IHC Assay for PD-L1 Detection in Non-Small Cell Lung Cancer
by Faye Willett, Marie MacLennan, Sihem Khelifa, Bharathi Vennapusa, Hannah Gautrey, Michael Parkin, Kate R Wilson, Kieran O’Toole, Shubham Dayal, Joseph Chiweshe, Robert Monroe and Fangru Lian
Biomedicines 2025, 13(10), 2359; https://doi.org/10.3390/biomedicines13102359 - 26 Sep 2025
Abstract
Background/Objectives: Programmed cell death-ligand 1 (PD-L1) is one of the key biomarkers for immune checkpoint inhibitors. We are developing a novel PD-L1 CAL10 immunohistochemistry (IHC) assay (Leica Biosystems) on BOND-III staining system and have analyzed its initial performance by comparing it to the [...] Read more.
Background/Objectives: Programmed cell death-ligand 1 (PD-L1) is one of the key biomarkers for immune checkpoint inhibitors. We are developing a novel PD-L1 CAL10 immunohistochemistry (IHC) assay (Leica Biosystems) on BOND-III staining system and have analyzed its initial performance by comparing it to the PD-L1 SP263 assay (Ventana) assay in a feasibility study. The study objective was to determine the concordance of the Leica Biosystems PD-L1 CAL10 assay with the comparator SP263 assay at the tumor proportion score (TPS) cutoff of ≥50% in non-small cell lung cancer (NSCLC) tissue samples. Additionally, the concordance between the two assays at the TPS cutoff of ≥1% was also evaluated. For informational purposes, we also evaluated the concordance between manual slide reads vs. digital reads (whole slide images generated using the Aperio GT 450) for the CAL10 assay. Methods: Two pathologists read and scored the glass slides. The CAL10 PD-L1 assay concordance with the PD-L1 SP263 assay was evaluated by assessing the agreement rates between the two assays. Results: The lower bound of the 95% confidence interval (CI) of the overall percent agreement (OPA) at ≥50% cutoff was 86.2%, while for ≥1% TPS cutoff, it was 94.0%, which met the predefined target of a minimum OPA lower bound of the 95% CI value of 85%. Conclusions: The Leica Biosystems CAL10 PD-L1 assay has demonstrated comparable performance to the SP263 assay. Additionally, the PD-L1 CAL10 stained glass slides and the corresponding whole side images generated by GT 450 showed comparable concordance rate. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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12 pages, 853 KB  
Article
Predictive Value of C-Reactive Protein/Albumin Ratio (CAR) for Malnutrition and Sarcopenia in Acute Ischemic Stroke Patients
by Hasan Dogan, Sugra Simsek, Ahmet Hakan Bayram, Aydan Topal, Mehlika Berra Pamuk, Ozkan Ozmuk, Nedim Ongun and Cetin Kursad Akpinar
J. Clin. Med. 2025, 14(19), 6804; https://doi.org/10.3390/jcm14196804 - 26 Sep 2025
Abstract
Background/Objective: Malnutrition and sarcopenia are common complications after ischemic stroke and have a negative impact on prognosis. The C-reactive protein/albumin ratio (CAR) reflects both inflammation and nutritional status, but its predictive role in this setting has not been widely studied. This study aimed [...] Read more.
Background/Objective: Malnutrition and sarcopenia are common complications after ischemic stroke and have a negative impact on prognosis. The C-reactive protein/albumin ratio (CAR) reflects both inflammation and nutritional status, but its predictive role in this setting has not been widely studied. This study aimed to investigate the predictive value of CAR (C-reactive protein/albumin ratio) for malnutrition risk and probable sarcopenia in patients with ischemic stroke. Methods: In this prospective observational study, 197 patients with acute ischemic stroke were evaluated. Patients with chronic renal or hepatic failure, malignancy, active infection, and hand disability preventing grip strength measurement were excluded. Demographic data (age, sex), vascular risk factors, the NIHSS score, and laboratory parameters were recorded. The nutritional status of patients was assessed using the Nutritional Risk Screening-2002 (NRS-2002), and sarcopenia risk was evaluated with the SARC-F questionnaire. Handgrip strength was measured in patients with high SARC-F scores to define probable sarcopenia. CAR was calculated from serum CRP and albumin levels. Logistic regression was applied to identify independent predictors, and receiver operating characteristic (ROC) analyses were performed to determine the discriminatory ability and cut-off values of CAR. The nutritional status of patients admitted to the neurology clinic with acute ischemic stroke was assessed using the Nutritional Risk Screening-2002 (NRS-2002), and sarcopenia risk was evaluated with the SARC-F questionnaire. Handgrip strength was measured in patients with high SARC-F scores to define probable sarcopenia. CAR was calculated from serum CRP and albumin levels. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: Malnutrition risk was identified in 32.5% of patients, and probable sarcopenia was identified in 19.3% of patients. ROC analysis showed that CAR had acceptable discriminatory power for both conditions. In multivariate analysis, CAR was consistently identified as an independent predictor of malnutrition risk and possible sarcopenia. ROC analysis for malnutrition risk showed an AUC of 0.750 (cut-off: 0.306; sensitivity 68.8%; specificity 75.2%). In regression analysis, CAR (OR = 2.13; 95% CI: 1.39–3.26; p < 0.001), age (OR = 1.05; 95% CI: 1.02–1.09; p = 0.003), and NIHSS (OR = 1.11; 95% CI: 1.01–1.23; p = 0.026) were independent predictors. For probable sarcopenia, ROC analysis revealed an AUC of 0.814 (cut-off: 0.320; sensitivity 81.6%; specificity 71.7%). Multivariate analysis identified CAR (OR = 1.73; 95% CI: 1.19–2.52; p = 0.004), age (OR = 1.11; 95% CI: 1.05–1.18; p < 0.001), and NIHSS (OR = 1.19; 95% CI: 1.05–1.35; p = 0.007) as independent predictors. Conclusions: CAR was identified as an independent predictor of both malnutrition risk and probable sarcopenia in ischemic stroke patients. CAR may serve as a reliable biomarker for early nutritional and functional risk stratification in clinical practice. Full article
(This article belongs to the Section Clinical Neurology)
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21 pages, 4606 KB  
Article
Targeting a Tau Kinase Cdk5, Cyclin-Dependent Kinase: A Blood-Based Diagnostic Marker and Therapeutic Earmark for Alzheimer’s Disease
by Sakshi Kumari, Abhinay Kumar Singh, Mukesh Kumar, Rashmita Pradhan, Abhijith R. Rao, Yudhishthir Yadav, Pramod Kumar, Partha Haldar, Punit Kaur and Sharmistha Dey
Biomolecules 2025, 15(10), 1365; https://doi.org/10.3390/biom15101365 - 26 Sep 2025
Abstract
Protein kinases are important molecules of Alzheimer’s Disease (AD), driving neuronal demise and the emergence of the disease’s destructive hallmarks. Cdk5 has recently been highlighted as a key therapeutic target for AD. This study evaluated the expression levels of Cdk5 and Mcl1 (Cdk5’s [...] Read more.
Protein kinases are important molecules of Alzheimer’s Disease (AD), driving neuronal demise and the emergence of the disease’s destructive hallmarks. Cdk5 has recently been highlighted as a key therapeutic target for AD. This study evaluated the expression levels of Cdk5 and Mcl1 (Cdk5’s substrate) in blood samples of 61 AD, 55 Mild Cognitive Impairment (MCI), and 57 Geriatric Controls (GC), and explored the in vitro inhibition of Cdk5. The serum levels of Cdk5 and Mcl1 were measured by Surface Plasmon Resonance (SPR) and verified by Western blot and RT-PCR. Molecular modeling and simulation studies were used to identify a potent hit targeting Cdk5 and validated by binding studies using SPR. The peptide rescue effect was analyzed by MTT assay in the AD cellular model. SPR analysis revealed a significant change in Cdk5 and Mcl1 levels in the serum samples of AD and MCI compared to GC. Results were validated by Western blot and RT-PCR. Binary logistic regression analysis revealed that the concentration of both Cdk5 and Mcl1 was independently associated with disease after adjusting for certain parameters. ROC analysis established an optimum diagnostic cutoff value for Cdk5 [24.97 ng/µL (AUC-0.90)] and Mcl1 [23.08 ng/µL (AUC-0.94)] with high sensitivity and specificity. The peptide YCWS strongly binds to Cdk5′s ATP binding site, confirmed by molecular modeling and SPR. In the AD cellular model, peptide YCWS rescued neurotoxicity, increased Mcl1 levels, and reduced destructive hallmarks by inhibiting Cdk5. It can be concluded that Cdk5 is a promising molecule as a circulatory biomarker for the diagnosis of the early stages of AD, and its peptide inhibitor YCWS is a potential therapeutic agent. Full article
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17 pages, 1422 KB  
Article
Development and Validation of an Owner-Assessed Feline Acute Pain Scale: Validation and Agreement with Veterinary Scales
by Samolwan Rojsiripornchai, Sirirat Niyom, Nattika Koatsang, Sakunrat Kathatip, Teerapat Thunpattranon, Wutti Bunjerdsuwan, Tassanee Jaroensong and Suwicha Kasemsuwan
Animals 2025, 15(19), 2801; https://doi.org/10.3390/ani15192801 - 25 Sep 2025
Abstract
Pain assessment in cats is challenging, especially for non-veterinarians. Most validated acute pain scales are designed for clinical use, limiting their applicability for pet owners. This study developed a feline acute pain assessment scale for owners and evaluated its criterion validity, internal consistency [...] Read more.
Pain assessment in cats is challenging, especially for non-veterinarians. Most validated acute pain scales are designed for clinical use, limiting their applicability for pet owners. This study developed a feline acute pain assessment scale for owners and evaluated its criterion validity, internal consistency reliability, and agreement with three veterinary scales: Glasgow Composite Measure Pain Scale-Feline (CMPS-Feline), Feline Grimace Scale (FGS), and Colorado State University Feline Acute Pain Scale (CSU-FPS). Of 146 enrolled cats, 130 were analyzed after exclusions. The owner-assessed scale showed strong correlation with CMPS-Feline (rho = 0.66) and moderate correlations with FGS (rho = 0.53) and CSU-FPS (rho = 0.57) (all p < 0.001). Agreement was substantial with CMPS-Feline (kappa = 0.74), moderate with FGS (kappa = 0.44), and fair with CSU-FPS (kappa = 0.28) (all p < 0.001). Internal consistency was acceptable (Cronbach’s alpha = 0.76). Receiver operating characteristic analysis demonstrated good discriminatory ability for identifying cats requiring analgesia, with area under the curve values of 0.87 (CMPS-Feline), 0.79 (FGS), and 0.75 (CSU-FPS). A cut-off score of 9 achieved 96% sensitivity and 78% specificity relative to CMPS-Feline. These results support the scale’s potential as a valid tool for pain detection by cat owners in non-clinical settings. Full article
(This article belongs to the Section Companion Animals)
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14 pages, 774 KB  
Article
Evaluation of Alpha1 Antitrypsin Deficiency-Associated Mutations in People with Cystic Fibrosis
by Jose Luis Lopez-Campos, Pedro García Tamayo, Maria Victoria Girón, Isabel Delgado-Pecellín, Gabriel Olveira, Laura Carrasco, Rocío Reinoso-Arija, Casilda Olveira and Esther Quintana-Gallego
J. Clin. Med. 2025, 14(19), 6789; https://doi.org/10.3390/jcm14196789 - 25 Sep 2025
Abstract
Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on [...] Read more.
Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/Plowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Clinical Manifestations and Treatment)
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16 pages, 841 KB  
Article
Trends in the Prevalence of Overweight, Obesity and Severe Obesity in Primary School Children in Croatia from 2003 to 2022
by Sanja Musić Milanović, Lucija Sironić, Ana Pezo, Helena Križan, Vesna Jureša and Vera Musil
Children 2025, 12(10), 1299; https://doi.org/10.3390/children12101299 - 25 Sep 2025
Abstract
Background: Childhood obesity remains a significant public health challenge globally. Croatia ranks among the leading European countries in terms of childhood overweight and obesity prevalence. Methods: The present cross-sectional study analysed overweight and obesity prevalence trends from 2003 to 2022 on a nationally [...] Read more.
Background: Childhood obesity remains a significant public health challenge globally. Croatia ranks among the leading European countries in terms of childhood overweight and obesity prevalence. Methods: The present cross-sectional study analysed overweight and obesity prevalence trends from 2003 to 2022 on a nationally representative sample containing data from five studies, two independent studies and three WHO COSI rounds. Data from a total of 11,817 children aged 7.00–8.99 were analysed. Weight categories were defined using the IOTF and WHO cut-offs. Overweight and obesity prevalence rates and trends overall and by sex and region were calculated, and binary regression models applied to investigate the relationship between the risk of overweight and several variables. p-value < 0.05 was used to define statistical significance. Results: Temporal trends and associations were investigated using the IOTF reference values. The prevalence of overweight (including obesity) had increased steadily from 2003 to 2015, thereafter continuing to increase at a slower rate, whereas the prevalence of severe obesity reduced over time. Even though boys had slightly higher prevalence rates of overweight, the growth in overweight prevalence in girls over time was significant. At the regional level, the lowest prevalence rates were detected in the capital (City of Zagreb region). The risk of overweight was at least 50% higher in all the other regions in Croatia, and a rising trend in overweight risk with time was particularly high among children in the Adriatic and Northern regions. Conclusions: Despite a deceleration in the rate of increase in overweight (including obesity) prevalence, Croatia is yet to reach a plateau observed in some other European countries. Unearthed regional differences warrant further investigation. Full article
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12 pages, 3099 KB  
Article
Evaluation of [11C]-Methionine Positron Emission Tomography and Cerebral Blood Volume Imaging in the Diagnosis of Non-Contrast-Enhanced Gliomas
by Naoya Imai, Hirohito Yano, Yuka Ikegame, Shoji Yasuda, Ryo Morishima, Soko Ikuta, Noriyuki Nakayama, Takashi Maruyama, Naoyuki Ohe, Morio Kumagai, Yoshihiro Muragaki, Jun Shinoda and Tsuyoshi Izumo
J. Clin. Med. 2025, 14(19), 6777; https://doi.org/10.3390/jcm14196777 - 25 Sep 2025
Abstract
Background/Objectives: Methionine (MET) positron emission tomography (PET) and cerebral blood volume (CBV) imaging provide complementary glioma assessment. This study compared MET and CBV across glioma subtypes defined by the 2021 World Health Organization Classification. Methods: This retrospective study enrolled 106 patients [...] Read more.
Background/Objectives: Methionine (MET) positron emission tomography (PET) and cerebral blood volume (CBV) imaging provide complementary glioma assessment. This study compared MET and CBV across glioma subtypes defined by the 2021 World Health Organization Classification. Methods: This retrospective study enrolled 106 patients (mean age 41.9 ± 12.4 years; 57 males) with MRI non-contrast-enhanced gliomas: 21 glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (G); 50 astrocytoma, IDH-mutant (A); and 35 oligodendrogliomas, IDH-mutant, and 1p/19q-codeleted (O). Relative CBVs (rCBVs) were measured in VOI-T2 and VOI-MET, and the MET tumor-to-normal (T/N) ratio was calculated. Results: MET and rCBV were significantly correlated (r = 0.5, p < 0.001); rCBV was higher in MET-positive tumors and predicted MET accumulation (area under the curve [AUC] = 0.72, cutoff = 2.99). In VOI-T2, rCBV and MET T/N ratio were the highest in G and lowest in A (p < 0.001). Receiver operating characteristic analyses showed no overall significant difference between MET and rCBV for differentiating G/A/O, but rCBV trended toward higher AUC values in key distinctions, such as G (0.736 vs. 0.612) or grade 4 (0.718 vs. 0.617). The increase in rCBV within the MET-positive region (VOI-MET/VOI-T2 rCBV ratio) was significantly higher in A (119.8%, p = 0.002) than in the other groups (p = 0.01). Conclusions: rCBV differentiated glioma subtype with accuracy comparable to MET and could predict MET accumulation. However, its reliability for identifying MET-positive regions varied by subtype, being useful in A but limited in O. Recognizing these subtype-specific differences, rCBV can serve as a practical tool for evaluating non-contrast-enhanced gliomas. Full article
(This article belongs to the Special Issue Revolutionizing Neurosurgery: Cutting-Edge Techniques and Innovations)
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16 pages, 911 KB  
Systematic Review
The Role of Perioperative Interleukin-6 Serum Levels on Liver Dysfunction and Infectious Complications After Hepatectomy—A Systematic Review
by Alexander Kofler, Marlene Trattner, Vivien Mairinger, Iveta Urban, Kjetil Søreide, Stefan Stättner and Florian Primavesi
Cancers 2025, 17(19), 3120; https://doi.org/10.3390/cancers17193120 - 25 Sep 2025
Abstract
Background: Interleukin-6 (IL-6) is used as a marker for infection and inflammation. After liver surgery, IL-6 is also crucial for hepatic regeneration. The value of IL-6 serum-levels to differentiate infection from imminent post-hepatectomy liver failure (PHLF) remains unclear. This review focuses on IL-6 [...] Read more.
Background: Interleukin-6 (IL-6) is used as a marker for infection and inflammation. After liver surgery, IL-6 is also crucial for hepatic regeneration. The value of IL-6 serum-levels to differentiate infection from imminent post-hepatectomy liver failure (PHLF) remains unclear. This review focuses on IL-6 and complications after liver resections, specifically PHLF and infections. Methods: A systematic review was performed in the PubMed, Embase, and Cochrane libraries from January 2000 to June 2025 according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). All English language human data publications were assessed. Results: Overall, 12 studies (n = 589 patients) evaluating perioperative serum IL-6 levels were included. Six publications reported PHLF rates, and two specifically addressed IL-6, PHLF, and infection. Several patient and surgical parameters influence IL-6 dynamics. Despite five randomized trials being published, the overall study quality was low, with a high risk of bias. In particular, IL-6 on the first postoperative day was associated with PHLF and infections, but multivariable analyses of confounding factors are lacking. A meta-analysis of studies with a specific cut-off calculation was precluded by heterogeneous cohorts and endpoints. Conclusions: IL-6 levels may have early diagnostic value regarding imminent infectious complications or PHLF early after liver resection, but the evidence is exploratory and limited by methodological weaknesses. At present, IL-6 as a single marker does not seem to show sufficient clinical discriminatory potential to differentiate between infection and impaired hepatic regeneration. Future studies should address confounding factors, ideal timepoints of assessment, different methods of serum IL-6 assays, specific cut-offs, and multi-marker combinations. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer Surgery)
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11 pages, 1393 KB  
Article
Elevated Serum Chromogranin-A and Characteristic Duodenal Enteroendocrine Cell Distribution in Pancreatic Fibrosis and Chronic Pancreatitis Compared with Other Dyspeptic Disorders: A Case Series Study
by Chung-Tsui Huang and Yao-Jen Liang
Diagnostics 2025, 15(19), 2428; https://doi.org/10.3390/diagnostics15192428 - 23 Sep 2025
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Abstract
Background: Prior research has reported increased expression of duodenal chromogranin-A (CgA), secreted by enteroendocrine cells (EECs), in association with pancreatic fibrosis. However, it remains unknown whether serum CgA levels are also elevated, and whether there is a different distribution pattern of EECs [...] Read more.
Background: Prior research has reported increased expression of duodenal chromogranin-A (CgA), secreted by enteroendocrine cells (EECs), in association with pancreatic fibrosis. However, it remains unknown whether serum CgA levels are also elevated, and whether there is a different distribution pattern of EECs in pancreatic fibrosis and other dyspeptic causes. Aims: This study had three main objectives. First, to compare the serum CgA level between patients with pancreatic fibrosis and those with other dyspeptic conditions. Second, to analyze the distribution pattern of duodenal EECs. Third, to evaluate whether biopsy results varied depending on the specific location within the duodenum. Serum CgA levels were categorized into low and high groups based on a cutoff value of 50 ng/mL. Methods: This cross-sectional prospective case series included 15 patients, with 4 patients in the low CgA group and 11 in the high CgA group. Each participant underwent a serum CgA test, transabdominal ultrasonography, pancreatic elastography, and upper gastrointestinal endoscopy. During endoscopy, a single gastric biopsy and three duodenal biopsies from different locations were obtained. Results: Patients in the high CgA group were generally older (52–68 years) than those in the low CgA group (37–55 years), with a statistically significant difference (p < 0.01). The high CgA group exhibited a clustered and centralized pattern of EECs, whereas the low CgA group showed a more discrete pattern with fewer EECs (p < 0.01). All duodenal ulcer cases were found in the low CgA group, while three cases of pancreatic fibrosis and one case of chronic pancreatitis were identified in the high CgA group. In the high CgA group, five cases of functional dyspepsia showed a band-like EEC distribution pattern, whereas cases with pancreatic fibrosis demonstrated a more uniformly scattered EEC distribution (p < 0.01). Consistency among intra-individual duodenal biopsy results was high across different biopsy sites. Conclusions: Elevated serum CgA (>50 ng/mL) and specific duodenal EEC distribution patterns may serve as potential diagnostic indicators for pancreatic fibrosis or chronic pancreatitis. These characteristics could help differentiate these conditions from functional dyspepsia. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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16 pages, 1068 KB  
Article
Impact of 68Ga-PSMA PET/MRI on the Accuracy of MRI-Derived Grading Systems for Predicting Extraprostatic Extension in Prostate Cancer
by Lebriz Uslu-Beşli, Selahattin Durmaz, Aslıhan Onay, Barış Bakır, İclal Gürses, Sevda Özel-Yıldız, Çetin Demirdağ and Haluk Burçak Sayman
Diagnostics 2025, 15(18), 2405; https://doi.org/10.3390/diagnostics15182405 - 22 Sep 2025
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Abstract
Objectives: Accurate preoperative staging and prediction of extraprostatic extension (EPE) are critical for optimal surgical planning in prostate cancer (PCa). This study evaluated the diagnostic accuracy of 68Ga-PSMA PET for EPE assessment, compared it with the standardized multiparametric MRI (mpMRI)-derived EPE-grading [...] Read more.
Objectives: Accurate preoperative staging and prediction of extraprostatic extension (EPE) are critical for optimal surgical planning in prostate cancer (PCa). This study evaluated the diagnostic accuracy of 68Ga-PSMA PET for EPE assessment, compared it with the standardized multiparametric MRI (mpMRI)-derived EPE-grading system, and examined whether integrating semi-quantitative PSMA PET parameters improves diagnostic performance using hybrid PET/MRI. Methods: This retrospective, single-center study included treatment-naïve, biopsy-proven PCa patients who underwent 68Ga-PSMA-11 PET/MRI followed by radical prostatectomy. Diagnostic accuracy was assessed for clinical variables (PSA, ISUP grade), mpMRI features, mpMRI-derived EPE-grading system, visual PET findings, and semi-quantitative PET parameters (SUVmax, SUVmean, PSMA-tumor volume [PSMA-TV]). Optimal cut-offs were determined using the Youden index. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed to compare the predictive value of clinical, mpMRI, or PET-derived variables, with histopathology as the reference standard. Results: Forty-five patients were included; EPE was histologically confirmed in 19 (42.2%). Predictors of EPE included capsular irregularity, neurovascular bundle asymmetry, curvilinear contact length ≥ 1.5 cm, seminal vesicle invasion, tumor size ≥ 14.25 mm, EPE grade ≥ 2, ISUP grade ≥ 3, overt EPE on PET, SUVmax ≥ 13.84, SUVmean ≥ 7.20, and PSMA-TV ≥ 1.40 cm3. The highest ROC performance (AUC = 0.890) was achieved by combining overt EPE on PET, SUVmax, and PSMA-TV. Incorporating PET parameters or tumor size into the EPE-grading system improved predictive accuracy. Conclusions: PSMA uptake in the primary tumor is an independent predictor of EPE. Integrating PSMA PET with mpMRI may provide additional information for preoperative EPE assessment. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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36 pages, 2290 KB  
Article
Diagnostic Biomarkers for Risk Estimation of In-Hospital and Post-Discharge Cardiovascular Mortality in ST-Segment Elevation Myocardial Infarction (STEMI) Patients
by Kristen Kopp, Michael Lichtenauer, Vera Paar, Uta C. Hoppe, Rozana F. Rakhimova, Elena A. Badykova, Eduard F. Agletdinov, Dimitry M. Grishaev, Ksenia A. Cheremisina, Anastasia V. Baraboshkina, Irina A. Lakman, Liya R. Abzalilova and Naufal S. Zagidullin
J. Clin. Med. 2025, 14(18), 6632; https://doi.org/10.3390/jcm14186632 - 20 Sep 2025
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Abstract
Background: ST-segment-elevation myocardial infarction (STEMI) continues to be associated with substantial short- and long-term cardiovascular (CV) mortality despite advances in treatment. Accurate early risk stratification remains critical for optimizing outcomes. Emerging biomarkers including CRP, sST2, and FABP may enhance predictive precision beyond [...] Read more.
Background: ST-segment-elevation myocardial infarction (STEMI) continues to be associated with substantial short- and long-term cardiovascular (CV) mortality despite advances in treatment. Accurate early risk stratification remains critical for optimizing outcomes. Emerging biomarkers including CRP, sST2, and FABP may enhance predictive precision beyond classical markers. This study aimed to evaluate the prognostic value of these biomarkers for in-hospital and 18-month post-discharge CV mortality in STEMI patients. Methods: In this prospective, single-center study, 179 consecutive STEMI patients admitted September 2020–June 2021 underwent biomarker evaluation upon admission. Serum concentrations of CRP, sST2, and H-FABP were measured by ELISA. Patients were followed for in-hospital outcomes and post-discharge mortality during 18-month follow-up (FU) (last patient, last visit January 2023). ROC analysis was used to determine biomarker cut-off values. Cox regression and Kaplan-Meier analyses assessed associations with mortality. Results: In-hospital mortality was 7.8% (14/179). Elevated CRP (>11 mg/L) was significantly associated with higher in-hospital mortality (21.4% vs. 3.7%, p < 0.01). sST2 and H-FABP showed trends toward worse outcomes at higher levels, although their independent predictive value was less robust. Cox regression identified CRP > 11 mg/L (HR = 4.93, p < 0.01), admission glucose, and reduced GFR as independent predictors of in-hospital mortality. During FU, 18 of 165 discharged patients (10.1%) experienced CV death. Higher sST2 levels were significantly associated with post-discharge mortality in midterm FU (p = 0.041). Conclusions: We could show that CRP > 11 mg/L is a strong predictor of in-hospital mortality while elevated sST2 is associated with CV mortality during midterm FU in STEMI patients. Incorporating these biomarkers into clinical risk models may enhance early risk prediction and identify patients at higher risk for post-discharge events. Full article
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12 pages, 701 KB  
Article
Blood-Based Inflammatory Markers Are Associated with Treatment Outcomes in Head and Neck Squamous Cell Carcinoma Receiving Anti-PD-1 Therapy: CRP as a Superior Predictive Marker
by Manuel Stöth, Flurin Müller-Diesing, Patricia Mack, Laura Ackermann, Corona Metz, Jan-Peter Grunz, Stephan Hackenberg, Miguel Goncalves, Thomas Gehrke, Till Jasper Meyer and Agmal Scherzad
Int. J. Mol. Sci. 2025, 26(18), 9154; https://doi.org/10.3390/ijms26189154 - 19 Sep 2025
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Abstract
Systemic inflammation is gaining increasing attention as a potential predictive biomarker in immune checkpoint inhibition (ICI) for head and neck squamous cell carcinoma (HNSCC). Several well-established blood-based inflammatory markers are commonly used to estimate systemic inflammatory burden. However, their utility in predicting treatment [...] Read more.
Systemic inflammation is gaining increasing attention as a potential predictive biomarker in immune checkpoint inhibition (ICI) for head and neck squamous cell carcinoma (HNSCC). Several well-established blood-based inflammatory markers are commonly used to estimate systemic inflammatory burden. However, their utility in predicting treatment outcomes in ICI for HNSCC remains unclear. This study aimed to evaluate the predictive value of the following inflammatory indices in patients with HNSCC receiving anti-PD-1 monotherapy: C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune inflammation index (SII). A total of 79 patients were included in this retrospective analysis. Optimal cutoff values were determined using receiver operating characteristic curve analysis to stratify patients into high- and low-inflammation groups. Chi-square tests were used to evaluate differences in treatment response. Progression-free survival (PFS) and overall survival (OS) were assessed and compared using Kaplan–Meier analysis and log-rank testing, alongside both univariable and multivariable Cox regression models. Elevated CRP levels were associated with a reduced disease control rate. In univariable analysis, patients in the high-inflammation groups showed significantly worse OS and PFS for all assessed inflammatory indices. In multivariable analysis, CRP and combined positive score remained independently significant predictors of both OS and PFS, while PLR was an independent predictor of OS. These findings suggest that a high level of systemic inflammation is associated with poorer outcomes during anti-PD-1 therapy in HNSCC. Among the evaluated indices, CRP stood out as an independent and clinically useful biomarker, providing a simple, widely available tool that could potentially serve as a practical instrument for clinicians in the management of HNSCC during anti-PD-1 treatment. Full article
(This article belongs to the Section Molecular Oncology)
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9 pages, 863 KB  
Article
Brainstem Glioma Prognostication: Static FET PET/CT
by Dávid Gergő Nagy, Júlia Singer and Katalin Borbély
Cancers 2025, 17(18), 3065; https://doi.org/10.3390/cancers17183065 - 19 Sep 2025
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Abstract
Background/Objectives: The classification and staging of brainstem glioma have its own pitfalls. Surgical biopsy is only possible in a small number of cases. Diagnosis relies mainly on radiological features. Any treatment may have a significant impact on quality of life; therefore, the correct [...] Read more.
Background/Objectives: The classification and staging of brainstem glioma have its own pitfalls. Surgical biopsy is only possible in a small number of cases. Diagnosis relies mainly on radiological features. Any treatment may have a significant impact on quality of life; therefore, the correct and early identification of potentially malignant lesions is essential to initiate proper therapy. Amino acid PET/CT with accurate metabolic mapping can help in this decision-making. Methods: We performed a retrospective analysis of 20 patients who underwent static FET PET/CT with uncertain brainstem lesions between November 2019 and April 2023. We used multiple tumor-to-brain ratios (TBR) to assess patient subgroups showing long-term and short-term survival. Results: The maximum Youden index was reached at TBR = 2.9. With this ratio, the estimated sensitivity was at the desired level (91.7%), both positive and negative predictive values are in the good performance range (68.8 and 75.0%), while specificity was lower than expected (37.5%). Conclusions: The prognosis of brainstem glioma remains challenging. The use of static FET PET/CT results in more accurate detection of high-grade lesions. In our analysis, we found a TBR value of 2.9 to be the most appropriate for identifying patients with a poor prognosis. Full article
(This article belongs to the Special Issue PET/CT and Conventional Imaging in Cancers)
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15 pages, 426 KB  
Article
Pan-Immune Inflammation Value as a Novel Comprehensive Predictor of In-Hospital Mortality in Patients with Severe Burns: A Single-Center Retrospective Analysis
by Hilmi Anil Dincer, Sara Koci, Omer Cennet and Ali Konan
Medicina 2025, 61(9), 1705; https://doi.org/10.3390/medicina61091705 - 19 Sep 2025
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Abstract
Background and Objectives: Despite the advances in the treatment, severe burns with total burn surface area ≥ 20% are still a major cause of mortality worldwide. Pan-immune inflammation value (PIV) is a novel and promising biomarker to predict prognosis and mortality in [...] Read more.
Background and Objectives: Despite the advances in the treatment, severe burns with total burn surface area ≥ 20% are still a major cause of mortality worldwide. Pan-immune inflammation value (PIV) is a novel and promising biomarker to predict prognosis and mortality in various diseases. The aim of this study was to evaluate the utility of PIV to predict in-hospital mortality of patients with severe burn. Materials and Methods: This retrospective cross-sectional study included ≥18 years old patients with severe burn who were admitted to hospital within 12–24 h after the burn injury between January 2007 and August 2024. The demographics, clinical and laboratory characteristics of patients were recorded from electronic hospital records. Pan-immune inflammation value was calculated as neutrophil counts x monocyte count x platelet counts divided by lymphocyte counts. The receiver operating characteristic (ROC) analysis was conducted to determine the predictive value of PIV for mortality. Results: A total of 100 patients (median age 41 (26.3–55) years; 79% male) were included in the study of whom 23 were non-survivors. The PIV was significantly higher in non-survivors when compared to survivors (p = 0.009). The ideal cut-off of PIV was 1185, with a sensitivity of 69.6% and a specificity of 66.2%. The multivariate analysis showed that high PIV along with inhalation injury, and the need for surgery were predictors of in-hospital mortality. Conclusions: This study is the first to demonstrate that the novel, comprehensive index, PIV, is a reliable immuno-inflammatory marker predicting in-hospital mortality in patients with severe burn. Full article
(This article belongs to the Section Surgery)
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14 pages, 1853 KB  
Article
Diagnostic Performance of a Laser Fluorescence Device for the In Vivo Detection of Occlusal Caries in Permanent Teeth
by Yuyeon Jung and Jun-Hyuk Choi
Appl. Sci. 2025, 15(18), 10208; https://doi.org/10.3390/app151810208 - 19 Sep 2025
Viewed by 215
Abstract
Dental caries remains one of the most prevalent global diseases, and the early detection of occlusal lesions is critical because demineralization often begins deep within pits and fissures where conventional visual–tactile or radiographic inspection cannot detect it. SmarTooth, a newly introduced fluorescence device [...] Read more.
Dental caries remains one of the most prevalent global diseases, and the early detection of occlusal lesions is critical because demineralization often begins deep within pits and fissures where conventional visual–tactile or radiographic inspection cannot detect it. SmarTooth, a newly introduced fluorescence device that irradiates enamel with a 655 nm laser and records the reflected intensity, may provide more objective, quantitative diagnoses. This study assessed its diagnostic performance against the International Caries Detection and Assessment System (ICDAS). We examined 1421 occlusal surfaces from 153 adults, scored each surface with ICDAS codes 0–4, and recorded SmarTooth peak values. Spearman’s rank correlation was used to test the association between codes and peak values; one-way ANOVA with Tukey’s post hoc was used to compare mean values across codes; and sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) were calculated at three diagnostic thresholds: D1 (0 vs. 1–4), D2 (0–2 vs. 3–4), and D3 (0–3 vs. 4). The SmarTooth values rose with lesion severity and correlated moderately with ICDAS (r = 0.495, p < 0.001). The AUROC ranged from 0.69 to 0.82, with the best accuracy observed at D2 (cut-off: 7.0; AUC: 0.82; sensitivity: 78.3%; specificity: 77.4%). These findings suggest that SmarTooth can complement ICDAS scoring as an adjunctive tool, potentially enhancing diagnostic accuracy and supporting early intervention for occlusal caries in general dental practice. Full article
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