Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (2,082)

Search Parameters:
Keywords = clinical system analyses

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
16 pages, 2235 KiB  
Article
Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma
by Tomoyuki Iwasaki, Hidekazu Shirota, Eiji Hishinuma, Shinpei Kawaoka, Naomi Matsukawa, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, Masanobu Takahashi, Chikashi Ishioka, Seizo Koshiba and Hisato Kawakami
Int. J. Mol. Sci. 2025, 26(15), 7528; https://doi.org/10.3390/ijms26157528 (registering DOI) - 4 Aug 2025
Abstract
Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host [...] Read more.
Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Genomics of Tumors)
Show Figures

Figure 1

14 pages, 279 KiB  
Article
FIB-4 Score as a Predictor of Eligibility for Elastography Exam in Patients with Polycystic Ovary Syndrome
by Maciej Migacz, Dagmara Pluta, Kamil Barański, Anna Kujszczyk, Marta Kochanowicz and Michał Holecki
Biomedicines 2025, 13(8), 1878; https://doi.org/10.3390/biomedicines13081878 - 1 Aug 2025
Viewed by 178
Abstract
Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an [...] Read more.
Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an association between PCOS and MASLD. This study was designed to compare the FIB-4 score (based on age, alanine aminotransferase, aspartate aminotransferase and platelet count) and the results of shear wave elastography in assessing the risk of developing MASLD by patients with PCOS divided by phenotypes. Methods: The study enrolled 242 women age 18–35 years with PCOS diagnosed according to Rotterdam criteria, hospitalized at the Department of Gynaecological Endocrinology of the University Clinical Centre in Katowice. The study subjects were assigned to phenotypes A to D. Clinical and biochemical assessments were performed (including androgens and metabolic parameters), and the FIB-4 index was calculated. Liver fibrosis was evaluated by shear wave elastography. To balance the group sizes of phenotypes, oversampling with replacement was applied (PROC SURVEYSELECT, SAS), increasing the number of observations for phenotypes B, C, and D fivefold. Statistical analyses were performed based on data distribution (Shapiro–Wilk test), using ANOVA or the Kruskal–Wallis test with Dunn’s correction. Statistical significance was set at p < 0.05. Results: The FIB-4 score was the highest in phenotype B patients (0.50 ± 0.15), and the lowest in phenotypes A and C (0.42 ± 0.14). The highest rate of positive elastography findings was recorded in phenotype A patients (34.7%) and the lowest in phenotype C group (13.5%). Significant differences between the phenotypes were also found in terms of androgen levels, insulin, HOMA-IR, and the lipid profile. Among patients with positive elastography, the highest FIB-4 scores were recorded in phenotype C group (0.44 ± 0.06), but the differences between the phenotypes were not statistically significant. Conclusions: The FIB-4 score was the highest in phenotype B patients and differed significantly from phenotypes A, C and D. In the elastography exam, the fibrosis index was statistically significantly higher in phenotype A compared to other phenotypes. No correlation was detected between the FIB-4 index and positive elastography. The findings suggest that the FIB-4 index may be used for MASLD screening, but its usefulness as a predictor of eligibility for elastography requires more research. Full article
15 pages, 651 KiB  
Article
The Impact of Comorbidities on Pulmonary Function Measured by Spirometry in Patients After Percutaneous Cryoballoon Pulmonary Vein Isolation Due to Atrial Fibrillation
by Monika Różycka-Kosmalska, Marcin Kosmalski, Michał Panek, Alicja Majos, Izabela Szymczak-Pajor, Agnieszka Śliwińska, Jacek Kasznicki, Jerzy Krzysztof Wranicz and Krzysztof Kaczmarek
J. Clin. Med. 2025, 14(15), 5431; https://doi.org/10.3390/jcm14155431 (registering DOI) - 1 Aug 2025
Viewed by 166
Abstract
Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality [...] Read more.
Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality of life, its impact on respiratory function is not well understood, particularly in patients with comorbid conditions. The aim of the study was to search for functional predictors of the respiratory system in the process of evaluating the efficiency of clinical assessment of CBA in patients with AF. Methods: We conducted a prospective study on 42 patients with symptomatic AF who underwent CBA, assessing their respiratory function through spirometry before and 30 days after the procedure. Exclusion criteria included pre-existing lung disease and cardiac insufficiency. The impact of variables such as body mass index (BMI), coronary artery disease (CAD) and heart failure (HF) on spirometry parameters was analyzed using statistical tests. Results: No significant changes were observed in overall post-PVI spirometry parameters for the full cohort. However, post hoc analyses revealed a significant decline in ΔMEF75 in patients with CAD and BMI ≥ 30 kg/m2, whereas ΔFEV1/FVCex was significantly increased in patients with HF, as well as in patients with ejection fraction (EF) < 50%. Conclusions: CBA for AF does not universally affect respiratory function in the short term, but specific subgroups, including patients with CAD and a higher BMI, may require post-procedure respiratory monitoring. In addition, PVI may improve lung function in patients with HF and reduced EF. Full article
(This article belongs to the Special Issue Clinical Aspects of Cardiac Arrhythmias and Arrhythmogenic Disorders)
Show Figures

Figure 1

13 pages, 1149 KiB  
Article
Not All Weight Loss Is Equal: Divergent Patterns and Prognostic Roles in Head and Neck Cancer Versus High-Grade B-Cell Lymphoma
by Judith Büntzel, Gina Westhofen, Wilken Harms, Markus Maulhardt, Alexander Casimir Angleitner and Jens Büntzel
Nutrients 2025, 17(15), 2530; https://doi.org/10.3390/nu17152530 - 31 Jul 2025
Viewed by 130
Abstract
Background: Malnutrition and unintended weight loss are frequent in cancer patients and linked to poorer outcomes. However, data on long-term weight trajectories, particularly comparing different cancer entities, remain limited. Methods: In this retrospective, multicenter study, we analyzed 145 patients diagnosed with either head [...] Read more.
Background: Malnutrition and unintended weight loss are frequent in cancer patients and linked to poorer outcomes. However, data on long-term weight trajectories, particularly comparing different cancer entities, remain limited. Methods: In this retrospective, multicenter study, we analyzed 145 patients diagnosed with either head and neck cancer (HNC; n = 48) or high-grade B-cell lymphoma (HGBCL; n = 97). Body weight, C-reactive protein (CrP), albumin, and modified Glasgow Prognostic Score (mGPS) were assessed at diagnosis and at 3, 6, 9, and 12 months. Clinically relevant weight loss was defined as >5% from baseline. Survival analyses were performed for HGBCL patients. Results: Weight loss was common in both cohorts, affecting 32.2% at 3 months and persisting in 42.3% at 12 months. Nearly half of HNC patients had sustained >5% weight loss at one year, whereas HGBCL patients were more likely to regain weight, with significantly higher rates of weight gain at 6 and 12 months (p = 0.04 and p = 0.02). At baseline, HGBCL patients showed elevated CrP and lower albumin compared to HNC (both p < 0.001). Weight loss at 6 months was significantly associated with reduced overall survival in HGBCL (p < 0.01). Both Δweight at 6 months and mGPS emerged as useful prognostic indicators. Conclusions: This study reveals distinct patterns of weight change and systemic inflammation between HNC and HGBCL patients during the first year after diagnosis. These findings highlight the need for entity-specific nutritional monitoring and tailored supportive care strategies extending into survivorship. Prospective studies integrating body composition analyses are warranted to better guide long-term management. Full article
Show Figures

Figure 1

22 pages, 716 KiB  
Article
Survival in Patients with Colorectal Cancer and Isolated Brain Metastases: Temporal Trends and Prognostic Factors from the National Cancer Database (2010–2020)
by Zouina Sarfraz, Diya Jayram, Ahmad Ozair, Lydia Hodgson, Shreyas Bellur, Arun Maharaj, Vyshak A. Venur, Sarbajit Mukherjee and Manmeet S. Ahluwalia
Cancers 2025, 17(15), 2531; https://doi.org/10.3390/cancers17152531 - 31 Jul 2025
Viewed by 143
Abstract
Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective [...] Read more.
Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective cohort study used the U.S. National Cancer Database to evaluate survival outcomes, treatment patterns, and prognostic factors in CRC patients diagnosed with BM between 2010 and 2020. Patients with isolated brain-only metastases formed the primary analytic cohort, while those with additional extracranial metastases were included for descriptive comparison. Multivariable Cox proportional hazards and logistic regression models were used to assess factors associated with of survival. Proportional hazards assumptions were tested using Schoenfeld residuals. Accelerated failure time models were also employed. Results: From a cohort of 1,040,877 individuals with CRC, 795 had metastatic disease present along with relevant data, of which 296 had isolated BM. Median overall survival (mOS) in BM-only metastatic disease group was 7.82 months (95% CI: 5.82–9.66). The longest survival was observed among patients treated with stereotactic radiosurgery combined with systemic therapy (SRS+Sys), with a median OS of 23.26 months (95% CI: 17.51–41.95) and a 3-year survival rate of 35.8%. In adjusted Cox models, SRS, systemic therapy, and definitive surgery of the primary site were each independently associated with reduced hazard of death. Rectal cancer patients had longer survival than those with colon primaries (mOS: 10.35 vs. 6.08 months). Age, comorbidity burden, and insurance status were not associated with survival in adjusted analyses. Conclusions: SRS+Sys was associated with longer survival compared to other treatment strategies. However, treatment selection is highly dependent on individual clinical factors such as performance status, comorbidities, and disease extent; therefore, these findings must be interpreted with caution Future prospective studies incorporating molecular and biomarker data are warranted to better guide care in this rare and high-risk group. Full article
(This article belongs to the Section Cancer Metastasis)
Show Figures

Figure 1

9 pages, 2757 KiB  
Article
Externally Triggered Activation of Nanostructure-Masked Cell-Penetrating Peptides
by Gayong Shim
Molecules 2025, 30(15), 3205; https://doi.org/10.3390/molecules30153205 - 30 Jul 2025
Viewed by 268
Abstract
Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon [...] Read more.
Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon complexation with a DNA-based nanostructure. Upon localized plasma exposure, DNA masking was disrupted, restoring the biological functions of the peptides. Transmission electron microscopy revealed that the synthesized DNA nanoflower structures were approximately 150–250 nm in size. Structural and functional analyses confirmed that the system remained inert under physiological conditions and was rapidly activated by plasma treatment. Fluorescence recovery, cellular uptake assays, and cytotoxicity measurements demonstrated that the peptide activity could be precisely controlled in both monolayer and three-dimensional spheroid models. This externally activatable nanomaterial-based system enables the spatial and temporal regulation of peptide function without requiring biochemical triggers or permanent chemical modifications. This platform provides a modular strategy for the development of potential peptide therapeutics that require precise control of activation in complex biological environments. Full article
(This article belongs to the Special Issue Nanomaterials for Advanced Biomedical Applications, 2nd Edition)
Show Figures

Figure 1

27 pages, 1869 KiB  
Review
Understanding the Molecular Basis of Miller–Dieker Syndrome
by Gowthami Mahendran and Jessica A. Brown
Int. J. Mol. Sci. 2025, 26(15), 7375; https://doi.org/10.3390/ijms26157375 - 30 Jul 2025
Viewed by 369
Abstract
Miller–Dieker Syndrome (MDS) is a rare neurodevelopmental disorder caused by a heterozygous deletion of approximately 26 genes within the MDS locus of human chromosome 17. MDS, which affects 1 in 100,000 babies, can lead to a range of phenotypes, including lissencephaly, severe neurological [...] Read more.
Miller–Dieker Syndrome (MDS) is a rare neurodevelopmental disorder caused by a heterozygous deletion of approximately 26 genes within the MDS locus of human chromosome 17. MDS, which affects 1 in 100,000 babies, can lead to a range of phenotypes, including lissencephaly, severe neurological defects, distinctive facial abnormalities, cognitive impairments, seizures, growth retardation, and congenital heart and liver abnormalities. One hallmark feature of MDS is an unusually smooth brain surface due to abnormal neuronal migration during early brain development. Several genes located within the MDS locus have been implicated in the pathogenesis of MDS, including PAFAH1B1, YWHAE, CRK, and METTL16. These genes play a role in the molecular and cellular pathways that are vital for neuronal migration, the proper development of the cerebral cortex, and protein translation in MDS. Improved model systems, such as MDS patient-derived organoids and multi-omics analyses indicate that WNT/β-catenin signaling, calcium signaling, S-adenosyl methionine (SAM) homeostasis, mammalian target of rapamycin (mTOR) signaling, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and others are dysfunctional in MDS. This review of MDS integrates details at the clinical level alongside newly emerging details at the molecular and cellular levels, which may inform the development of novel therapeutic strategies for MDS. Full article
(This article belongs to the Special Issue Rare Diseases and Neuroscience)
Show Figures

Figure 1

20 pages, 15855 KiB  
Article
Resistance Response and Regulatory Mechanisms of Ciprofloxacin-Induced Resistant Salmonella Typhimurium Based on Comprehensive Transcriptomic and Metabolomic Analysis
by Xiaohan Yang, Jinhua Chu, Lulu Huang, Muhammad Haris Raza Farhan, Mengyao Feng, Jiapeng Bai, Bangjuan Wang and Guyue Cheng
Antibiotics 2025, 14(8), 767; https://doi.org/10.3390/antibiotics14080767 - 29 Jul 2025
Viewed by 290
Abstract
Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, [...] Read more.
Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
Show Figures

Figure 1

21 pages, 1762 KiB  
Article
Kinetics of Procalcitonin, CRP, IL-6, and Presepsin in Heart Transplant Patients Undergoing Induction with Thymoglobulin (rATG)
by Lorenzo Giovannico, Vincenzo Ezio Santobuono, Giuseppe Fischetti, Federica Mazzone, Domenico Parigino, Luca Savino, Maria Alfeo, Aldo Domenico Milano, Andrea Igoren Guaricci, Marco Matteo Ciccone, Massimo Padalino and Tomaso Bottio
J. Clin. Med. 2025, 14(15), 5369; https://doi.org/10.3390/jcm14155369 - 29 Jul 2025
Viewed by 296
Abstract
Background/Objectives: Heart transplantation (HTx) is a lifesaving procedure for end-stage heart failure patients; however, postoperative infections remain a major challenge due to immunosuppressive therapy and surgical complications. Traditional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) have limitations in distinguishing infections [...] Read more.
Background/Objectives: Heart transplantation (HTx) is a lifesaving procedure for end-stage heart failure patients; however, postoperative infections remain a major challenge due to immunosuppressive therapy and surgical complications. Traditional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) have limitations in distinguishing infections from systemic inflammatory response syndrome (SIRS). Emerging markers such as Presepsin and interleukin-6 (IL-6) may improve diagnostic accuracy. This study aimed to evaluate the kinetics and reliability of these four inflammatory biomarkers in heart transplant recipients in the immediate postoperative period. Methods: This retrospective observational study included 126 patients who underwent HTx at Policlinic of Bari between January 2022 and November 2024. Patients were categorized into infected (n = 26) and non-infected (n = 100) groups based on clinical and microbiological criteria. Biomarkers (CRP, PCT, Presepsin, and IL-6) were measured preoperatively and on postoperative days (PODs) 1, 2, 3, 4, 5, and 10. Statistical analyses included the Mann–Whitney U test and logistic regression to identify the independent predictors of infection. Results: CRP and PCT levels differed significantly between the groups only on day 10, limiting their use as early infection markers. In contrast, Presepsin levels were significantly elevated in infected patients from day 1 (p < 0.001), whereas IL-6 levels showed significant differences from day 3 onward. Presepsin showed the strongest association with infection in the early postoperative phase. Conclusions: Presepsin and IL-6 outperformed CRP and PCT in detecting early postoperative infections in heart transplant recipients. Their early elevation supports their use as reliable markers for guiding timely clinical intervention and improving patient outcomes. Further research is needed to validate these findings in larger cohorts and with different immunosuppressive regimens. Full article
(This article belongs to the Section Cardiology)
Show Figures

Graphical abstract

15 pages, 1343 KiB  
Article
Prognostic Value of Metabolic Tumor Volume and Heterogeneity Index in Diffuse Large B-Cell Lymphoma
by Ali Alper Solmaz, Ilhan Birsenogul, Aygul Polat Kelle, Pinar Peker, Burcu Arslan Benli, Serdar Ata, Mahmut Bakir Koyuncu, Mustafa Gurbuz, Ali Ogul, Berna Bozkurt Duman and Timucin Cil
Medicina 2025, 61(8), 1370; https://doi.org/10.3390/medicina61081370 - 29 Jul 2025
Viewed by 493
Abstract
Background and Objectives: Metabolic tumor volume (MTV) and inflammation-based indices have recently gained attention as potential prognostic markers of diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the prognostic significance of metabolic and systemic inflammatory parameters in predicting treatment response, relapse, [...] Read more.
Background and Objectives: Metabolic tumor volume (MTV) and inflammation-based indices have recently gained attention as potential prognostic markers of diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the prognostic significance of metabolic and systemic inflammatory parameters in predicting treatment response, relapse, and overall survival (OS) in patients with DLBCL. Materials and Methods: This retrospective cohort study included 70 patients with DLBCL. Clinical characteristics, laboratory values, and metabolic parameters, including maximum standardized uptake value (SUVmaxliver and SUVmax), heterogeneity indices HI1 and HI2, and MTV were analyzed. Survival outcomes were assessed using Kaplan–Meier and log-rank tests. Receiver operating characteristic analyses helped evaluate the diagnostic performance of the selected biomarkers in predicting relapse and mortality. Univariate and multivariate logistic regression analyses were conducted to identify the independent predictors. Results: The mean OS and mean relapse-free survival (RFS) were 71.6 ± 7.4 and 38.7 ± 2.9 months, respectively. SUVmaxliver ≤ 22 and HI2 > 62.3 were associated with a significantly shorter OS. High lactate dehydrogenase (LDH) levels and HI2 > 87.9 were significantly associated with a reduced RFS. LDH, SUVmaxliver, and HI2 had a significant predictive value for relapse. SUVmaxliver and HI2 levels were also predictive of mortality; SUVmaxliver ≤ 22 and HI2 > 62.3 independently predicted mortality, while HI2 > 87.9 independently predicted relapse. MTV was not significantly associated with survival. Conclusions: Metabolic tumor burden and inflammation-based markers, particularly SUVmaxliver and HI2, are significant prognostic indicators of DLBCL and may enhance risk stratification and aid in identifying patients with an increased risk of relapse or mortality, potentially guiding personalized therapy. Full article
(This article belongs to the Section Oncology)
Show Figures

Figure 1

13 pages, 1130 KiB  
Article
Feasibility and Preliminary Results of a Standardized Stair Climbing Test to Evaluate Cardiorespiratory Fitness in Children and Adolescents in a Non-Clinical Setting: The “Hand Aufs Herz” Study
by Federico Morassutti Vitale, Jennifer Wieprecht, Maren Baethmann, Delphina Gomes, Anja Tengler, Roxana Riley, Samar Shamas, Marcel Müller, Guido Mandilaras, Simone Katrin Manai, Maria Jaros, Nikolaus Alexander Haas and Meike Schrader
Children 2025, 12(8), 993; https://doi.org/10.3390/children12080993 - 28 Jul 2025
Viewed by 298
Abstract
Background/Objectives: Cardiorespiratory fitness (CRF) is of great interest in children and adolescents. Due to the limited availability of cardiopulmonary exercise testing, simple and reliable alternatives are needed. A stair climbing test (SCT) for the assessment of CRF developed at the Department of [...] Read more.
Background/Objectives: Cardiorespiratory fitness (CRF) is of great interest in children and adolescents. Due to the limited availability of cardiopulmonary exercise testing, simple and reliable alternatives are needed. A stair climbing test (SCT) for the assessment of CRF developed at the Department of Pediatric Cardiology of the LMU University Hospital in Munich showed a strong correlation with VO2max. The aim of this study is to prove its feasibility in a non-clinical setting and to analyse its results in a larger study population. Methods: During the “Hand aufs Herz” study, a comprehensive cardiovascular examination was carried out on 922 pupils and siblings (13.2 ± 7.8 years) at a high school in Bavaria. The SCT was performed to evaluate CRF: participants had to run up and down a total of four floors (14.8 m) as quickly as possible without skipping steps or holding on to the banister. Absolute time has been normalized over the standard height of 12 m to allow comparisons with different settings. An SCT Index was calculated to adjust results to the different weights of participants and the exact height of the staircase. Results: The SCT proved to be easily feasible and safe in non-clinical contexts. Out of 922 participants, 13 (1.4%) were not able to perform the test, and 3 (0.3%) had to interrupt it following fatigue or stumbling. A total of 827 participants aged from 9 to 17 years (13.1 ± 2.1 years, 45.8% girls) had a mean absolute SCT time of 53.4 ± 6.2 s and 43.3 ± 5.1 s when normalized over 12 m. Conclusions: The SCT represents a simple, cost- and time-saving test that allows a rapid and solid assessment of cardiorespiratory fitness in children and adolescents. We could demonstrate that it is safe and feasible in non-clinical contexts. Its short duration and universal applicability are valuable advantages that could facilitate the establishment of a repetitive cardiovascular screening in the pediatric population, particularly in outpatient departments or settings with low-resource systems. Full article
(This article belongs to the Special Issue Prevention of Cardiovascular Diseases in Children and Adolescents)
Show Figures

Figure 1

13 pages, 1017 KiB  
Article
Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis
by Ionut-Valentin Stanciu, Ariadna-Petronela Fildan, Adrian Cosmin Ilie, Cristian Oancea, Livia Stanga, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Doina-Ecaterina Tofolean, Ionela Preotesoiu, Viorica Zamfir and Elena Dantes
J. Clin. Med. 2025, 14(15), 5327; https://doi.org/10.3390/jcm14155327 - 28 Jul 2025
Viewed by 277
Abstract
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised [...] Read more.
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL−1 vs. 16.2 pg mL−1; p = 0.009) and IL-1β (5.34 pg mL−1 vs. 3.67 pg mL−1; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL−1) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL−1 rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m−2) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article
(This article belongs to the Section Infectious Diseases)
Show Figures

Figure 1

34 pages, 1544 KiB  
Review
The Crucial Interplay Between the Lungs, Brain, and Heart to Understand Epilepsy-Linked SUDEP: A Literature Review
by Mohd Yaqub Mir, Bilal A. Seh, Shabab Zahra and Adam Legradi
Brain Sci. 2025, 15(8), 809; https://doi.org/10.3390/brainsci15080809 - 28 Jul 2025
Viewed by 361
Abstract
Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective [...] Read more.
Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. Full article
Show Figures

Graphical abstract

23 pages, 2002 KiB  
Article
Precision Oncology Through Dialogue: AI-HOPE-RTK-RAS Integrates Clinical and Genomic Insights into RTK-RAS Alterations in Colorectal Cancer
by Ei-Wen Yang, Brigette Waldrup and Enrique Velazquez-Villarreal
Biomedicines 2025, 13(8), 1835; https://doi.org/10.3390/biomedicines13081835 - 28 Jul 2025
Viewed by 441
Abstract
Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of [...] Read more.
Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks. To address this challenge, we developed AI-HOPE-RTK-RAS, a domain-specialized conversational artificial intelligence (AI) system designed to enable natural language-based, integrative analysis of RTK-RAS pathway alterations in CRC. Methods: AI-HOPE-RTK-RAS employs a modular architecture combining large language models (LLMs), a natural language-to-code translation engine, and a backend analytics pipeline operating on harmonized multi-dimensional datasets from cBioPortal. Unlike general-purpose AI platforms, this system is purpose-built for real-time exploration of RTK-RAS biology within CRC cohorts. The platform supports mutation frequency profiling, odds ratio testing, survival modeling, and stratified analyses across clinical, genomic, and demographic parameters. Validation included reproduction of known mutation trends and exploratory evaluation of co-alterations, therapy response, and ancestry-specific mutation patterns. Results: AI-HOPE-RTK-RAS enabled rapid, dialogue-driven interrogation of CRC datasets, confirming established patterns and revealing novel associations with translational relevance. Among early-onset CRC (EOCRC) patients, the prevalence of RTK-RAS alterations was significantly lower compared to late-onset disease (67.97% vs. 79.9%; OR = 0.534, p = 0.014), suggesting the involvement of alternative oncogenic drivers. In KRAS-mutant patients receiving Bevacizumab, early-stage disease (Stages I–III) was associated with superior overall survival relative to Stage IV (p = 0.0004). In contrast, BRAF-mutant tumors with microsatellite-stable (MSS) status displayed poorer prognosis despite higher chemotherapy exposure (OR = 7.226, p < 0.001; p = 0.0000). Among EOCRC patients treated with FOLFOX, RTK-RAS alterations were linked to worse outcomes (p = 0.0262). The system also identified ancestry-enriched noncanonical mutations—including CBL, MAPK3, and NF1—with NF1 mutations significantly associated with improved prognosis (p = 1 × 10−5). Conclusions: AI-HOPE-RTK-RAS exemplifies a new class of conversational AI platforms tailored to precision oncology, enabling integrative, real-time analysis of clinically and biologically complex questions. Its ability to uncover both canonical and ancestry-specific patterns in RTK-RAS dysregulation—especially in EOCRC and populations with disproportionate health burdens—underscores its utility in advancing equitable, personalized cancer care. This work demonstrates the translational potential of domain-optimized AI tools to accelerate biomarker discovery, support therapeutic stratification, and democratize access to multi-omic analysis. Full article
Show Figures

Figure 1

13 pages, 617 KiB  
Article
Management and Outcomes of Blunt Renal Trauma: A Retrospective Analysis from a High-Volume Urban Emergency Department
by Bruno Cirillo, Giulia Duranti, Roberto Cirocchi, Francesca Comotti, Martina Zambon, Paolo Sapienza, Matteo Matteucci, Andrea Mingoli, Sara Giovampietro and Gioia Brachini
J. Clin. Med. 2025, 14(15), 5288; https://doi.org/10.3390/jcm14155288 - 26 Jul 2025
Viewed by 298
Abstract
Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are [...] Read more.
Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are primarily dictated by hemodynamic stability, overall clinical condition, comorbidities, and injury severity graded according to the AAST classification. This study aimed to evaluate the effectiveness of non-operative management (NOM) in high-grade renal trauma (AAST grades III–V), beyond its established role in low-grade injuries (grades I–II). Secondary endpoints included the identification of independent prognostic factors for NOM failure and in-hospital mortality. Methods: We conducted a retrospective observational study including patients diagnosed with blunt renal trauma who presented to the Emergency Department of Policlinico Umberto I in Rome between 1 January 2013 and 30 April 2024. Collected data comprised demographics, trauma mechanism, vital signs, hemodynamic status (shock index), laboratory tests, blood gas analysis, hematuria, number of transfused RBC units in the first 24 h, AAST renal injury grade, ISS, associated injuries, treatment approach, hospital length of stay, and mortality. Statistical analyses, including multivariable logistic regression, were performed using SPSS v28.0. Results: A total of 244 patients were included. Low-grade injuries (AAST I–II) accounted for 43% (n = 105), while high-grade injuries (AAST III–V) represented 57% (n = 139). All patients with low-grade injuries were managed non-operatively. Among high-grade injuries, 124 patients (89%) were treated with NOM, including observation, angiography ± angioembolization, stenting, or nephrostomy. Only 15 patients (11%) required nephrectomy, primarily due to persistent hemodynamic instability. The overall mortality rate was 13.5% (33 patients) and was more closely associated with the overall injury burden than with renal injury severity. Multivariable analysis identified shock index and active bleeding on CT as independent predictors of NOM failure, whereas ISS and age were significant predictors of in-hospital mortality. Notably, AAST grade did not independently predict either outcome. Conclusions: In line with the current international literature, our study confirms that NOM is the treatment of choice not only for low-grade renal injuries but also for carefully selected hemodynamically stable patients with high-grade trauma. Our findings highlight the critical role of physiological parameters and overall ISS in guiding management decisions and underscore the need for individualized assessment to minimize unnecessary nephrectomies and optimize patient outcomes. Full article
(This article belongs to the Special Issue Emergency Surgery: Clinical Updates and New Perspectives)
Show Figures

Figure 1

Back to TopTop