Search Results (7,020)

Background/Objectives: Malnutrition is highly prevalent in patients with acute leukemia and is frequently underrecognized at diagnosis. Traditional screening tools based on anthropometry often fail to identify early nutritional deterioration. This study aimed to evaluate the prognostic utility of a comprehensive morphofunctional assessment—including bioelectrical impedance vector analysis (BIVA), handgrip strength (HGS), and muscle ultrasound—conducted at diagnosis and after induction therapy, to evaluate the prognostic association with 12-month mortality. Methods: In this prospective cohort study, 52 adult patients with newly diagnosed acute leukemia were enrolled between November 2022 and November 2024 at two tertiary hospitals in Málaga, Spain. Nutritional status was determined using GLIM criteria. Morphofunctional assessment included BIVA-derived phase angle (PhA), HGS via dynamometry, and rectus femoris ultrasound. A second evaluation was performed prior to haematopoietic stem cell transplantation. Mortality at 12 months was the primary outcome. Logistic regression and ROC analysis were used to assess prognostic associations. Results: At baseline, 65.4% of patients were classified as malnourished. After three months, patients showed significant declines in PhA (−0.55°, p < 0.001), body cell mass (−3.15 kg, p < 0.01), skeletal muscle mass (−1.66 kg, p < 0.01), and rectus femoris cross-sectional area (−0.36 cm², p = 0.011). Baseline malnutrition (OR = 6.88; 95% CI: 1.17–40.38; p = 0.033) and PhA decline ≥ 0.90° were both independently associated with higher 12-month mortality. Conclusions: Early morphofunctional assessment using GLIM criteria, BIVA, and muscle ultrasound identifies patients at nutritional and functional risk. PhA decline during treatment was associated with higher 12-month mortality, supporting the need for early, personalized nutritional intervention in leukemia care. Full article

Background/Objectives: Despite the long-standing history of liver transplantation (LT) in Spain, no multicenter study has reviewed national outcomes for LT in metastatic neuroendocrine tumors (NETs). In the current era of transplant oncology, auditing these results is essential to refine patient selection and improve long-term outcomes. Methods: This retrospective observational study analyzed data from 13 centers, including 91 patients who underwent LT for NET between 1995 and 2024. Patients were stratified into two groups: Milan IN (those meeting the Milan criteria) and Milan OUT (the remainder). Results: Recurrence occurred in 57.1% of cases, and overall mortality was 51.6%. Of the 91 patients, 71 (78.0%) were Milan IN and 20 (22.0%) were Milan OUT. Five-year overall survival was 71.0% in Milan IN and 58.0% in Milan OUT, with a statistically significant difference. The 5-year disease-free survival (DFS) rate was 58.8% in Milan IN and 36.3% in Milan OUT; this difference was not statistically significant. Conclusions: In conclusion, strict adherence to Milan criteria and incorporation of modern prognostic factors are critical to optimize long-term survival in LT for NET. While the overall outcomes in this historical cohort are modest, future improvements are expected through more rigorous selection and the potential use of bridging or downstaging therapies. Full article

Background: People with Parkinson’s disease suffer from gait impairments. Clinical scales provide a limited and rater-dependent assessment of gait. Wearable sensors allow an objective characterization by capturing rhythm, pace, and signature patterns. This study investigated if sensor-derived gait parameters have prognostic value for short-term progression of gait impairments. Methods: A total of 111 longitudinal visit pairs were analyzed, where participants underwent clinical evaluation and a 4 × 10 m walking test instrumented with wearable sensors. Changes in the UPDRSIII gait score between baseline and follow-up were used to classify participants as Improvers, Stables, or Deteriorators. Baseline group differences were assessed statistically. Machine-learning classifiers were trained to predict group membership using clinical variables alone, sensor-derived gait features alone, or a combination of both. Results: Significant between-group differences emerged. In participants with UPDRSIII gait score = 1, Improvers showed higher median gait velocity ($0.81 \mathrm{m}/\mathrm{s}$) and stride length ($0.80 \mathrm{m}$) than Stables ($0.68 \mathrm{m}/\mathrm{s}$; $0.70 \mathrm{m}$) and Deteriorators ($0.59 \mathrm{m}/\mathrm{s}$; $0.68 \mathrm{m}$), along with lower stance time variability (3.10% vs. 4.49% and 3.75%; all $p<0.05$). The combined sensor-based and clinical model showed the best performance (AUC $0.82$). Conclusions: Integrating sensor-derived gait parameters with clinical score can support the identification of patients at risk of gait deterioration in the near future. Full article

Background: Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of four autophagy pathway components (BECLIN, p62/, LC3b, ATG3) in pathogenetic mechanisms of thymic epithelial tumors (TETs) with possible prognostic importance. Methods: Immunohistochemistry was used to evaluate the cytoplasmic expression of BECLIN, p62, LC3b, and ATG3 in tumor cells of 99 TETs, and possible correlations with clinicopathological parameters were examined. Results: Higher BECLIN and p62 expression was associated with male gender (p = 0.027 and p = 0.014, respectively). B3 thymomas and thymic carcinomas (TCs) displayed higher p62 expression (p = 0.019), while LC3b expression was marginally higher in non-B3/TC TETs (p = 0.098). A positive correlation between higher BECLIN expression and advanced Masaoka–Koga stage was also observed (p = 0.009). ATG3 was not associated with any of the investigated clinicopathological parameters (p > 0.05). There was also no significant correlation between any of the four examined molecules and overall survival or relapse. Conclusions: Our findings indicate autophagy activation in B3/TC and advanced Masaoka–Koga stage cases. Further studies are needed to explore the role of these autophagy related proteins as potential biomarkers and therapeutic targets in TETs. Full article

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease (ESRD). Progressive renal cyst growth in ADPKD can exert mass effects, including compression of the inferior vena cava (IVC), a rare but clinically significant complication with implications for hemodynamic stability and renal outcomes. This study evaluated the prevalence of IVC compression in ADPKD and its impact on progression to ESRD, mortality, and overall survival. We aimed to provide quantitative measures to elucidate its prognostic significance. Materials and Methods: Using the TriNetX database, we conducted a retrospective cohort study of 658 ADPKD patients with IVC compression, comparing them to unmatched controls without compression. Outcomes included ESRD incidence, mortality, and survival. Kaplan–Meier curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for analysis. Results: ESRD Risk: IVC compression was associated with a higher risk of ESRD (77.4% vs. 29.7%, RR: 2.61, 95% CI: 2.49–2.73, p < 0.001). Survival Probability: 5-year Survival was significantly reduced in patients with IVC compression (42.6%) compared to controls (61.7%) (HR: 4.00, 95% CI: 3.45–4.63, p = 0.002). Mortality: Mortality was higher in the compression group (29.2% vs. 9.1%). Combined Impact: ESRD patients with IVC compression had a lower survival rate (11.9%) than ESRD patients without compression (28.5%) (HR: 5.60, 95% CI: 5.12–6.13, p < 0.001). Conclusions: IVC compression in ADPKD is associated with significantly worse outcomes, including increased ESRD risk, higher mortality, and reduced survival. These findings underscore the importance of early diagnosis and targeted management strategies. Full article

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, and immune activation—including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), β2-microglobulin, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—have emerged as promising alternatives. This study evaluated early post-transplant serum profiles of these biomarkers and their prognostic relevance for long-term graft outcomes. Methods: Nineteen adult recipients undergoing primary kidney transplantation were prospectively enrolled. Serum creatinine and protein biomarkers were measured 24 h post-transplant using validated immunochemical assays. Biomarker concentrations were compared with values from healthy controls, and correlations with renal function at 12 months were assessed. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance. Results: Significant biochemical alterations were observed at 24 h post-transplant. KIM-1 levels were markedly elevated compared with controls (74.50 ± 98.45 vs. 10.54 ± 17.19 ng/mL; p = 0.01), consistent with early tubular injury. IL-1β and NGAL showed upward trends without reaching statistical significance. β2-microglobulin and TNF-α levels did not differ substantially from control values. Serum KIM-1 correlated with serum creatinine both at 24 h (r = 0.35) and at 12 months (r = 0.40). ROC analysis identified a KIM-1 threshold of 24.5 ng/mL (AUC = 0.68) as a potential indicator of future graft dysfunction, outperforming serum creatinine (AUC = 0.64). Six patients experienced graft dysfunction at 12 months post-transplant, five of whom had serum creatinine values > 5 mg/dL at 24 h. Based on early creatinine levels, patients were stratified into low-risk (creatinine < 5 mg/dL; n = 10) and high-risk groups (creatinine > 5 mg/dL; n = 9). Mean KIM-1 concentrations were significantly higher in the high-risk group (110.68 ± 115.29 vs. 26.67 ± 18.05 ng/mL; p = 0.05), consistent with more severe early tubular injury. Conclusions: Among the evaluated biomarkers, KIM-1 demonstrated the strongest potential as an early biochemical indicator of renal allograft dysfunction. Its rapid post-transplant elevation underscores its sensitivity to early tubular injury. Further prospective validation in larger, multicenter cohorts is warranted. Full article

Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related mortality worldwide, highlighting the urgent need for novel therapeutic targets. While the role of the somatostatin receptor (SSTR) family is well established in neuroendocrine tumors, their expression patterns, clinical significance, and therapeutic potential in LUAD are not fully understood. In this study, comprehensive analyses of publicly available databases, including TCGA, GSCA, and TIMER, revealed that SSTR4 transcriptional expression is significantly downregulated in LUAD tissues compared to adjacent normal lung tissues. Moreover, low SSTR4 expression correlates with advanced tumor stage, remodeling of the immune microenvironment, and decreased overall survival in patients with LUAD. Using the PRESTO-Tango system, we identified tangeretin (TAN) as a potential ligand for SSTR4. Functional assays demonstrated that SSTR4 knockdown markedly enhanced TAN-mediated proliferative, migratory, and survival inhibitory effects in LUAD cells. Subsequent RNA sequencing and pathway enrichment analyses revealed that the loss of SSTR4 altered the effects of TAN from extracellular matrix remodeling to disruption of calcium homeostasis and energy metabolism disorders, elucidating the mechanism underlying the enhanced antitumor activity. Collectively, these findings establish SSTR4 as a critical tumor suppressor and prognostic biomarker in LUAD and highlight the therapeutic potential of targeting the TAN–SSTR4 signaling axis. These results provide novel insights into the biological functions of SSTR family members in LUAD. Full article

Ovarian cancer remains the most lethal gynaecological malignancy primarily due to late-stage diagnosis, high recurrence rate, and limited treatment efficacy. Current diagnostic tools, including imaging and serum markers, lack sufficient sensitivity and specificity for early detection. Increasing evidence highlights the critical role of myeloid-derived immune cells within the tumour microenvironment in shaping ovarian cancer progression and therapy response. Monocytes and their derivatives are central regulators of immune suppression, chemoresistance, and metastatic dissemination in ovarian tumours. Their recruitment and polarisation are governed by several signalling pathways offering promising therapeutic targets. Strategies including monocyte depletion, TAM reprogramming, MDSC maturation, DC vaccines, and their synergistic use with chemotherapy or immune checkpoint inhibitors are being explored to restore anti-tumour immunity in ovarian cancer. Parallel to therapeutic potential, the lymphocyte-to-monocyte ratio and its reciprocal monocyte-to-lymphocyte ratio have also emerged as potential accessible and cost-effective prognostic tools that predict disease aggressiveness and survival in ovarian cancer. This review features the diagnostic, prognostic, and therapeutic significance of monocytes and their derivatives in ovarian cancer management and highlighting new opportunities for next-generation immunomodulatory therapies. Full article

Cellular senescence, characterized by permanent cell cycle arrest, significantly influences cancer development, immune regulation, and progression. However, the precise mechanisms by which senescence contributes to colorectal cancer prognosis remain to be fully elucidated. By integrating expression profiles of senescence-related and prognostic genes in colon adenocarcinoma (COAD) patients, we formulated and confirmed a nine-gene cellular senescence-related signature (CSRS) that integrates senescence-associated and prognosis-predictive genes using data from the CellAge, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A cell senescence-related prognostic formula was developed as follows: CSRS = (CASP2 × 0.2098) + (CDKN2A × 0.1196) + (FOXD1 × 0.1472) + (ING5 × 0.3723) + (OXTR × 0.0786) + (PHGDH × 0.1408) + (SERPINE1 × 0.1127) + (SNAI1 × 0.1034) + (LIMK1 × 0.0747). In a multivariate Cox proportional hazards model, the CSRS score, age and TNM stage were all identified as significant independent indicators for overall survival, affirming their prognostic value in colorectal cancer. The CSRS-high group exhibited significantly up-regulated senescence-associated secretory phenotype (SASP) and immune cell infiltration, whereas the CSRS-low group showed an apparent better response to immune-checkpoint inhibitor therapy. Our findings suggest CSRS score and its constituent genes represent potential biomarkers for prognosis and immunotherapeutic benefit in COAD patients. Extending this nine-gene set into a broader senescence-associated panel should be a next step toward delivering truly individualized treatment plans. Full article

MicroRNAs are key post-transcriptional regulators in breast cancer, but their time-dependent dynamics and downstream oncogenic effects are not fully understood. miR-548c-3p has been proposed as a tumor suppressor, yet its temporal behavior and impact on cell cycle drivers remain unclear. This study investigated the time-dependent expression of miR-548c-3p and its post-transcriptional regulation of E2F3 and FOXM1 in MCF-7 breast cancer cells. Cells were analyzed at multiple time points (2–72 h) by quantitative real-time PCR to assess dynamic changes in miR-548c-3p, E2F3, and FOXM1 mRNA levels. Bioinformatic validation using TCGA-BRCA datasets and public platforms evaluated gene expression, promoter methylation, and prognostic significance. miR-548c-3p showed a progressive time-dependent decline, with the lowest levels at 72 h, whereas E2F3 and FOXM1 were significantly upregulated over time, supporting a post-transcriptional derepression mechanism. TCGA-based analyses confirmed overexpression and hypomethylation of E2F3 and FOXM1 in breast cancer, particularly in triple-negative tumors, and high expression of both genes was associated with poor survival. These findings indicate that time-dependent loss of miR-548c-3p contributes to E2F3 and FOXM1 activation through a post-transcriptional regulatory mechanism, highlighting this miRNA–oncogene axis as a potential prognostic signature and therapeutic target in breast cancer. Full article

Feline calicivirus (FCV) is a highly variable RNA virus that infects domestic cats and circulates endemically within feline populations, causing a wide spectrum of clinical manifestations, from asymptomatic infections to severe disease. Genomic analysis of 69 FCV strains revealed a high prevalence of the virus across multiple provinces in China. In vitro infection of CRFK cells with laboratory isolates FCV-BJ616 and FCV-BJDX40 resulted in significant cytotoxic effects. Serum proteomic analysis identified 221 upregulated and 123 downregulated proteins following infection with FCV-BJ616, and 233 upregulated and 165 downregulated proteins following infection with FCV-BJDX40. Among these, 215 proteins exhibited shared differential expression. Functional analyses revealed enriched pathways, including TNF signaling and ferroptosis. Notably, upregulation of Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) was correlated with lung injury, while downregulation of S100 Calcium Binding Protein A2 (S100A2) was associated with poor prognosis in FCV-associated oral disease. The differential expression of ACSL4 and S100A2 was further validated through Western blot analysis. These results suggest that ACSL4 and S100A2 are promising candidate biomarkers for monitoring FCV infection and disease progression, laying a foundation for future diagnostic and prognostic applications. Full article

Although the impact of COVID-19, caused by SARS-CoV-2, may appear to have diminished in recent years, the emergence of new variants still continues to cause significant global health and economic challenges. While numerous metabolomic studies have explored serum-based alterations linked to the infection, investigations utilizing urine as a biological matrix remain notably limited. This gap is especially significant given the potential advantages of urine, a non-invasive and easily obtainable biofluid, in clinical settings. In the context of patients in intensive care units (ICUs), temporal monitoring through such non-invasive samples may offer a practical and effective approach for tracking disease progression and tailoring therapeutic interventions. This study retrospectively explored the longitudinal metabolomic alterations in COVID-19 patients admitted to the ICU, stratified into three prognostic outcome groups: healthy discharged (HD), polyneuropathic syndrome (PS), and Exitus. A total of 32 urine samples, collected at four distinct time points per patient during April 2020 and preserved at −80 °C, were analyzed by proton nuclear magnetic resonance (¹H-NMR) spectroscopy for comprehensive metabolic profiling. Statistical evaluation using two-way ANOVA and ANOVA–Simultaneous Component Analysis (ASCA) identified significant prognostic variations (p < 0.05) in the levels of taurine, 3-hydroxyvaleric acid and formic acid. Complementary supervised classification via random forest modeling yielded moderate predictive performance with out-of-bag error rate of 40.6% based on prognostic categories. Particularly, taurine, 3-hydroxyvaleric acid and formic acid levels were highest in the PS group. However, no significant temporal changes were observed for any metabolite in analyses. Additionally, metabolic pathway analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the “taurine and hypotaurine metabolism” pathway as the most significantly affected (p < 0.05) across prognostic classifications. Harnessing urinary metabolomics, as indicated in our preliminary study, could offer valuable insights into the dynamic metabolic responses of ICU patients, thereby facilitating more personalized and responsive critical care strategies in COVID-19 patients. Full article

Background: Insulin resistance (IR) has been implicated in cardiovascular diseases, and a correlation between IR and the slow flow phenomenon (CSF)has been identified. The triglyceride–glucose index (TGI), a simple surrogate marker for IR, has recently emerged as a potential predictor of CSF, though data are limited. The aim of this study was to evaluate the association of TGI and other prognostic parameters in patients with CSF. Methods: This retrospective study included 693 patients who underwent diagnostic coronary angiography between January 2022 and December 2024. A total of 132 patients were diagnosed with CSF based on the corrected TIMI frame count (cTFC > 27 in at least one epicardial coronary artery), while 561 patients had normal coronary flow (NCF). Patients with confounding cardiovascular or systemic conditions were excluded. Clinical, demographic, and laboratory data were gathered, and TGI was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2].Results: Statistically significant distinctions were found between the CSF and NCF groups regarding TGI, age, glucose, HbA1c, creatinine, sodium, CRP, platelet count, heart rate, PR interval, and cQT interval (p < 0.05). Age, hypertension, diabetes mellitus, HbA1c, glucose, sodium, and cQT were identified as potential clinical and laboratory factors associated with CSF in univariate logistic regression analysis; however, no independent predictor was found in multivariate analysis. ROC analysis showed that a TGI cut-off value of ≥8.93 predicted CSF with 67.6% sensitivity and 66.7% specificity. Conclusions: Our study demonstrated that TGI was significantly greater in patients with CSF compared to those with NCF. Although TGI showed limited sensitivity and specificity in discriminating CSF, its possible value as a prognostic indicator warrants further validation in prospective, large-scale studies. Full article

Viper envenomation in dogs represents a significant medical emergency in regions where vipers are endemic. Despite its clinical relevance, detailed data on the haematological and biochemical alterations in canine viper envenomation remain limited. This study aimed to evaluate the clinical presentation and haematological, biochemical and coagulative changes occurring in dogs following bites from the Vipera aspis species, and to assess their diagnostic and prognostic significance. Twelve dogs with suspected Vipera aspis envenomation were encompassed in the study. Clinical data were gathered and blood samples were collected at hospital admission (T1), 24 h (T2) and 48 h later (T3). Complete blood counts, biochemical profiles and coagulation parameters were analysed using standard automated systems. Common clinical signs included local pain and swelling, depression, fever, haematuria and melena. Haematological evaluation revealed progressive anaemia, leucocytosis and thrombocytopenia. Biochemical findings showed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and creatine kinas (CK), indicating hepatic and muscular injury; however, no consistent evidence of renal failure was found. Coagulation analysis revealed a significant shortening of activated partial thromboplastin time (aPTT) and prothrombin time (PT) over time, alongside marked increases in fibrinogen and antithrombin III. This indicates an inflammatory rather than consumptive coagulopathy. Viper envenomation in dogs induces complex haematological and biochemical alterations, reflecting both direct venom toxicity and systemic inflammatory responses. Early recognition, supportive care and continuous laboratory monitoring are essential for improving prognosis. Full article

Background: Gastric cancer (GC) is one of the most common malignancies, requires aggressive treatment, as has a high incidence of complications. The high prevalence of cachexia and comorbidity among GC patients has led to the development of the “prehabilitation” concept. We aimed to investigate the prognostic value of cachexia in the “Western” patient population with resectable GC and to evaluate its utility as an indicator for a home-based prehabilitation program. Methods: This cohort study included 147 patients who underwent surgical treatment for GC from 2019 to 2023. A multivariable analysis was conducted to study the impact of cachexia on postoperative outcomes in 122 patients with resectable GC. The prehabilitation group included 25 patients with cachexia who underwent a 2-week-long multimodal prehabilitation program prior to surgery. The functional results, as well as the 30-day incidence of postoperative complications and 90-day mortality, were evaluated. Results: There were 76 (51.7%) patients with cachexia. Multivariate analysis revealed that cachexia was a significant predictor of all postoperative complications (OR = 5.48, 95% CI 1.85–18.39, p = 0.001), severe postoperative complications (OR = 15.87, 95% CI 3.05–131.81, p < 0.001) and surgical site infection (SSI) (OR = 8.03, 95% CI 1.89–49.09, p = 0.038). Patients in the prehabilitation group had a lower incidence of SSI than in the control group (8.3% vs. 23.5%, p = 0.049). Conclusions: Preoperative cachexia is a potentially modifiable predictor of complications after gastric cancer surgery, and its identification may help define high-risk patients for proactive multimodal prehabilitation. Full article