Search Results (9,998)

Background: Canine lymphoma comprises the majority of haematopoietic malignancies in veterinary clinical practice. Several prognostic factors have been studied and, more recently, there has been an increased interest in the role of the lymphocyte-to-monocyte ratio (LMR) for its prognostic value. To date, the prognostic value of absolute monocyte and lymphocyte counts as well as LMR at the time of relapse in dogs with diffuse large B-cell lymphoma has not been evaluated. The purpose of the present study was to investigate whether the absolute monocyte, lymphocyte or LMR at relapse can predict clinical outcomes for relapsed diffuse large B-cell lymphoma dogs treated with chemotherapy. Additionally, the parameters were evaluated for their prognostic value at the time of diagnosis and throughout different timepoints during the course of their first-line chemotherapy treatment. Materials and Methods: We retrospectively analysed data from 50 dogs with relapsed diffuse large B-cell lymphoma, treated with a CEOP-based first-line chemotherapy protocol. Lymphocyte and monocyte count and LMR were evaluated at different timepoints: at diagnosis, during chemotherapy and at the time of relapse. Overall survival time (OS) and disease-free interval (DFI), as well as overall survival time from relapse (OS_r), were measured. Friedman nonparametric ANOVA was used to compare blood cell counts at different timepoints. Spearman rank correlation was used to test for association between blood cell count at various timepoints with the duration of remission and survival time. Results: Monocyte and lymphocyte counts and LMR at the time of first relapse were not found to be adverse prognostic factors for OS_r in this population of dogs. Monocyte and lymphocyte counts differed significantly between different timepoints during the chemotherapy protocol. Conclusions: Absolute monocyte and lymphocyte counts and LMR at the time of relapse were not found to be prognostic indicators of OS_r in this population of dogs with multicentric lymphoma. Additional studies evaluating absolute monocyte and lymphocyte counts during chemotherapy treatment and following completion of chemotherapy in larger population of dogs are needed to assess whether these counts have clinical utility in detecting disease progression. Full article

Oxidative stress (OS) reflects a pathologic imbalance between excessive production of reactive oxygen species (ROS) and insufficient antioxidant defenses. Growing evidence indicates that a healthy gut microbiota (GM) is essential for regulating redox homeostasis, whereas gut dysbiosis contributes to elevated ROS levels and oxidative damage in DNA, lipids, and proteins. This redox disequilibrium initiates a cascade of cellular disturbances—including synaptic dysfunction, altered receptor activity, excitotoxicity, mitochondrial disruption, and chronic neuroinflammation—that can, in turn, impair cognitive and social functioning in metabolic and neuropsychiatric disorders via epigenetic mechanisms. In this review, we synthesize current knowledge on (1) how OS contributes to cognitive and social deficits through epigenetic dysregulation; (2) the role of disrupted one-carbon metabolism in epigenetically mediated neurological dysfunction; and (3) mechanistic links between leaky gut, OS, altered GM composition, and GM-derived epigenetic metabolites. We also highlight emerging microbiota-based therapeutic strategies capable of mitigating epigenetic abnormalities and improving cognitive and social outcomes. Understanding the OS–microbiota–epigenetic interplay may uncover new targetable pathways for therapies aimed at restoring brain and behavioral health. Full article

Objective: To evaluate the real-world efficacy and safety of disitamab vedotin (RC48-ADC) in patients with human epidermal growth factor receptor 2 (HER2) overexpression (immunohistochemistry [IHC] 2+ or 3+), advanced gastric/gastroesophageal junction cancer (GC/GEJC) with metastases who had received at least one line of prior systemic therapy. Patients and methods: Patients with HER2-overexpressing advanced or metastatic GC/GEJC who had previously received the anti-HER2 antibody-drug conjugate disitamab vedotin between December 2022 and April 2024 were enrolled in this study. The patients’ baseline characteristics, treatment procedures, and laboratory or imaging examinations were retrospectively collected and analyzed. The observation items included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: Of the 38 enrolled patients in the study, 27 were found to be HER2-positive. Most patients (29/38) received disitamab vedotin therapy as a third-line or subsequent treatment. A total of 68.4% of patients had previously received anti-HER2 therapy, and 13 patients underwent immunotherapy concurrently. The overall ORR and DCR were 31.6% and 65.8%, respectively. A higher ORR was observed in patients with a single metastatic site compared to those with multiple sites (53.3% vs. 17.4%, p = 0.022). In the general population, the median PFS was 6.5 months (95% confidence interval [CI] 3.3–9.8 months), and OS was 13.5 months (95% CI 9.0–17.9 months). The most common adverse event was anemia (89.5%), and eight patients suffered severe toxicities of grade ≥3. Conclusions: Disitamab vedotin exhibited encouraging anti-tumor effectiveness with a tolerable safety profile for advanced GC/GEJC patients with HER2 overexpression who had failed at least one line of systemic therapy in a real-world setting. Full article

Background: Multiple meta-analyses have compared liver resection (LR) with liver transplantation (LT) for hepatocellular carcinoma (HCC), but overlapping primary studies and heterogeneous outcome definitions have complicated interpretation. Methods: A PRISMA/PRIOR-compliant umbrella review (PROSPERO CRD420251069248) was conducted. PubMed, Embase, and CENTRAL were searched for meta-analyses published between 1 January 2000 and 30 September 2025. Quantitative meta-analyses comparing LT and LR were included, while one systematic review of meta-analyses was synthesised narratively. Effect directions were standardised; hazard ratio (HR)-based summaries (LR:LT; values > 1 favour LT) were pooled using random-effects models, whereas odds ratio (OR)-based summaries were described qualitatively because of heterogeneity in endpoint definitions. Results: Four quantitative meta-analyses and one systematic review of meta-analyses met the inclusion criteria. Pooled HRs confirmed LT superiority: overall survival (OS) HR 1.35 (95% CI 1.17–1.55) and disease-free survival (DFS) HR 2.58 (95% CI 2.25–2.96). OR-based summaries from recent meta-analyses were directionally consistent but were not pooled. Conclusions: This umbrella synthesis demonstrates that LT provides superior long-term OS and DFS compared with LR for HCC, with consistent robustness across both Milan and extended selection criteria. Methodological safeguards against study overlap and subgroup insights—including intention-to-treat analyses, viral etiology (hepatitis B virus/hepatitis C virus), era, and geographic region—reinforce LT as the preferred strategy for eligible patients, while LR remains a critical option where graft availability is limited. Full article

Oil pollution poses a persistent threat to soil ecosystems globally, and bioremediation using bacterial consortia has emerged as a cost-effective remediation strategy. However, the role of weak petroleum-degrading bacteria in enhancing the efficiency of specialized petroleum-degrading bacteria remains unclear. This study explores the synergy and remediation potential of a two-bacterial consortium: the petroleum-degrading bacterium Rhodococcus sp. OS62-1 and the weak petroleum-degrading bacterium Pseudomonas sp. P35. A 25-day microcosm experiment was conducted with petroleum-contaminated soil, and four treatments were set: (1) uninoculated control, (2) inoculation with Rhodococcus sp. OS62-1 alone, (3) inoculation with Pseudomonas sp. P35 alone, and (4) inoculation with the consortium. Soil samples were collected periodically to analyze petroleum degradation efficiency, soil enzyme activities (dehydrogenase, catalase, polyphenol oxidase, and lipase), and microbial community composition (16S rRNA gene sequencing). Inoculating the soils with this consortium produced a higher petroleum degradation rate, microbial activity, and soil enzyme activity than inoculation with strain OS62-1 or P35 alone. Inoculation with strain P35 also contributed to the maintenance of strain OS62-1 during bioremediation. The study of microbial community structure found that the relative abundance of phylum Acidobacteriota (57.6 ± 5.3% to 75.6 ± 8.1%) and the Nocardioides genus (36.4 ± 4.5% to 53.0 ± 9.2%) increased dramatically during the bioremediation process. Pearson’s correlation analysis revealed that inoculation with strain OS62-1 and/or strain P35 increases the soil enzyme activity, boosts native oil-degrading bacteria, and accelerates the degradation of petroleum contaminants. Molecular ecological networks analysis revealed that inoculation with strain OS62-1 and/or strain P35 increased the complexity and robustness of the microbial network. These findings confirm that weak petroleum-degrading bacteria can synergistically enhance the bioremediation efficiency of specialized petroleum-degrading bacteria, providing a practical strategy for optimizing the design of bacterial consortia in the bioremediation of oil-polluted soils. Full article

Circulating tumor DNA (ctDNA) analysis offers a non-invasive approach to molecular profiling. While RAS mutations are well-established predictive biomarkers in metastatic colorectal cancer (mCRC), the prognostic value of their variant allele frequency (VAF) remains unclear. We retrospectively analyzed individual patient data with mCRC who underwent ctDNA testing using the FoundationOne^® Liquid CDx assay. The primary objective was to determine the optimal RAS VAF cutoff for overall survival (OS) prognostication. Between November 2020 and July 2024, 282 patients were enrolled. Among 265 eligible patients, 134 (50.6%) were ctRAS mutant, 25 (9.4%) ctBRAF^V600E mutant, and 106 (40.0%) were ctRAS/BRAF wild-type. A RAS VAF threshold of 5% yielded the highest prognostic discrimination for OS (HR = 2.41; 95% CI 1.65–3.55; p < 0.0001; C-index = 0.601). ctRAS-high mutant tumors (VAF ≥ 5%) were associated with synchronous metastatic disease, multiple metastatic sites, higher blood tumor mutational burden, and elevated tumor fraction. ctRAS-low mutant tumors (VAF < 5%) were more frequently metachronous, presented with a single metastatic site, and showed liver involvement. High RAS VAF in ctDNA is a strong and independent prognostic marker for OS in mCRC. Quantitative ctDNA profiling may enhance risk stratification and guide personalized management strategies. Full article

Background: Clear cell renal cell carcinoma (RCC) is the most common primary tumor that metastasizes to the pancreas, and surgery is the established treatment option. The aim of this study was to compare surgical treatment options for RCC metastases to the pancreas and to assess long-term outcomes, identifying risk factors for recurrence and death. Methods: We retrospectively analyzed data from 62 patients with RCC metastases to the pancreas who underwent pancreatic surgery at the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice. Patients were divided into two groups: those who underwent local tumor removal (group A, N = 10) and those who underwent classical pancreatic resection (group B, N = 52). Demographic data, postoperative course, histological findings, and clinical outcomes—recurrence-free survival (PFS) and overall survival (OS)—were analyzed. Results: In group A, tumors were smaller (p < 0.001) and exclusively single (p = 0.100), and Clavien–Dindo complications were milder, with a predominance of grade 0 (90% vs. 28.8%; p = 0.042). In group B, blood loss was greater (p < 0.001), and hospitalization was longer (median 12.5 days vs. 10.5 days; p = 0.022) compared with group A. Group A had a longer PFS (144 months vs. 61 months; p = 0.007) and longer OS (144 months vs. 70 months; p = 0.006) compared with group B. In the entire cohort, independent factors associated with worse OS in multivariate analysis were larger tumor size (p = 0.003), lymphatic invasion (p < 0.001), vascular invasion (p < 0.001), perineural invasion (p < 0.001), R1 resection (p < 0.001), and symptoms of the metastases (p < 0.001). Conclusions: The prognosis following surgical resection of pancreatic RCC metastases is excellent: median OS is 77 months, and 5-year survival reaches 71.4%. In multivariate analysis, the type of surgical treatment is not significantly associated with OS or PFS. The choice of surgical procedure should depend on the preoperative CT results and the intraoperative assessment of the surrounding tissues. Full article

Diabetes mellitus (DM) is a complex, heterogeneous, hyperglycemic chronic metabolic disorder. Type 2 diabetes mellitus (T2DM) is characterized by progressive loss of insulin secretion from pancreatic islet β-cells due to IR (insulin resistance), which is a feature of metabolic syndrome (MetS). Chronic hyperglycemia in patients with T2DM in synergy with other metabolic abnormalities causes complications such as diabetic ketoacidosis, osmotic diuresis and hyperglycemic diabetic coma, as well as chronic microvascular and macrovascular complications such as atherosclerotic cardiovascular disease (ASCVD), peripheral artery disease (PAD) and cerebrovascular events, which implicate the formation of reactive species and the promotion of inflammatory pathways. In these events, natural or synthetic antioxidants and minerals seem to have ameliorative effects and may serve as beneficial co-treatment options. In view of these terms, the aim of this study is to investigate the underlying mechanisms of T2DM, its clinical presentation, and its complications. Additionally, the association of the pathogenesis of T2DM and the occurrence of its complications with obesity, chronic inflammation, oxidative stress (OS), insulin resistance (IR), hepatic steatosis, and dyslipidemia is examined, whilst molecular pathways, such as NF-κB and JAK/STAT, are also summarized, under the scope of the effects of several antioxidant compounds and minerals on their progression. The interrelation of T2DM with these conditions, as well as the effects of antioxidant supplementation, seems to be bidirectional, and it is recommended that obese patients be screened for T2DM and adopt lifestyle changes, including exercise, diet modification, and weight loss, in addition to potentially taking multifunctional supplements that offer antioxidant and anti-inflammatory potential. However, many aspects of the protective mechanisms of such antioxidants remain to be elucidated, with more drawbacks in their pharmacokinetic behavior, such as their poor absorption and solubility, waiting to be resolved. Full article

Background: Pregnancy-associated breast cancer (PABC), defined as breast cancer diagnosed during pregnancy or within one year postpartum, is a unique and clinically challenging entity. Evidence suggests that tumors diagnosed during pregnancy (PrBC) and postpartum (PPBC) may differ in biology and prognosis. This study compares clinical features, treatment patterns and outcomes between PrBC and PPBC. Methods: We performed a retrospective analysis of 76 women diagnosed with PABC from January 2000 to June 2023 across two tertiary centers. Patients were classified according to ESMO guidelines as PrBC (n = 41) or PPBC (n = 35). Clinical presentation, tumor characteristics, treatment approaches and survival outcomes were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier analysis and compared with log-rank tests. Results: A total of 76 patients with PABC were included (41 PrBC, 35 PPBC; median age 37 years). Most tumors were high-grade invasive ductal carcinomas, with Luminal B predominant in PrBC and triple-negative breast cancer (TNBC) in PPBC. Locally advanced disease was common (axillary involvement 52%; de novo metastases 9%). Surgery was performed in most cases, with breast conservative surgery (BCS) more frequent in PrBC and mastectomy in PPBC; 46% received neoadjuvant chemotherapy. At median follow-up of 68 months, 7.9% of patients had died and 29% experienced recurrence. Oncologic outcomes were similar between subgroups, with a trend in favor of PrBC. Pregnancy continuation did not adversely affect outcomes. Conclusions: PrBC and PPBC display heterogeneous clinical presentations with a trend toward more favorable outcomes in PrBC. These findings support the need for tailored counseling, individualized management and research designs that differentiate between PrBC and PPBC. Full article

Conventional and electronic cigarette (e-cig) users face an increased risk of cardiorespiratory diseases, driven by well-characterized pathways involving inflammation and oxidative stress (OS). Conventional cigarettes contain numerous harmful chemicals, such as nicotine and non-nicotine compounds, which produce reactive oxygen species. Although initially considered a safer alternative, the e-cig still generates toxic aldehydes that are capable of triggering oxidative responses. Heart rate variability (HRV) is an important tool for assessing autonomic function and predicting prognosis. Cardiac autonomic dysfunction, indicated by reduced HRV, has emerged as a critical cardiovascular risk factor associated with several diseases. Clinical and experimental studies show that increased OS is directly associated with heightened sympathetic activity and inversely with parasympathetic modulation. This review demonstrates that exposure to conventional cigarettes smoking and e-cigs adversely affects cardiac autonomic function, detectable by a global reduction in HRV that reflects a shift toward sympathetic dominance and a consequent increase in cardiovascular risk. These changes are associated with increased OS due to nicotine and non-nicotine compounds maintaining sympathovagal imbalance in smokers. Thus, we suggest that autonomic dysfunction, detected by HRV, correlates with oxidative responses and may be used as a modifiable risk factor in longitudinal studies involving both smoking modalities. Full article

Background: Haploidentical hematopoietic cell transplantations (haplo-HCTs) with post-transplant cyclophosphamide (PT-Cy) are standard practice, but complications causing morbidity and mortality are not well described. Methods: The aim of this prospective non-interventional multicenter study was to document frequency of potential non-infectious and infection-related complications and main transplant outcomes after the first unmanipulated haplo-HCT with PT-Cy between 2017 and 2019 in 129 adult patients with hematological malignancies. The median follow-up was 37.3 months [95% CI: 34.3–39.7]. Results: The cumulative incidence (CI) of acute graft versus host disease (aGvHD) at day +100 was 22.4% grade II-IV [95% CI: 15.5–30.1] and 8.8% grade III-IV [95% CI: 4.6–14.6], respectively. The cumulative incidence of chronic GvHD (cGvHD) at 24 months was 25.8% [95% CI: 18.5–33.6]; extensive cGvHD was 10.9% [95% CI: 6.3–17.1], respectively. The most frequent non-infectious complications for the whole study population were mucositis—37.5% (n = 48); renal insufficiency—18% (n = 23); and cardiovascular complications—10.9% (n = 14). The following infection-related complications were diagnosed: bacterial in 84 (65.1%), viral in 66 (51.6%), and fungal in 24 (18.6%) recipients. Two-year OS was 58.1% [95% CI: 50.2–67.3]; NRM—27.1% [95% CI: 19.7–35]; PFS—50.4% [95% CI: 42.5–59.8]; and GRFS—38.8% [95% CI: 31.2–48.1]. About 50% of all deaths were directly caused by infection or infection-related conditions. Conclusions: Disease remission status at transplant significantly affected PFS, chronic GvHD, and GRFS. Although clinical applications of haplo-HCT with PTCy are widespread, the study confirms the need to reduce infection-related mortality after this type of GvHD prophylaxis. Full article

Background and Objectives: Grade 4 adult-type diffuse gliomas remain the most aggressive primary central nervous system malignancies, with limited prognostic tools beyond molecular classification. This study introduces the HALLMOUNT score, a multidimensional prognostic index integrating hematologic, biochemical, and clinical parameters to capture the interplay between tumor biology and systemic host response. Materials and Methods: A total of 227 patients with histologically confirmed grade 4 adult-type diffuse glioma were retrospectively analyzed. The HALLMOUNT score incorporated nine pretreatment variables: hemoglobin, albumin, lactate dehydrogenase (LDH), lymphocyte, monocyte, Eastern Cooperative Oncology Group (ECOG) performance status, uric acid, neutrophil, and thrombocyte counts. Receiver operating characteristic (ROC) analyses determined optimal cut-offs, and Cox regression models evaluated prognostic performance for overall (OS) and progression-free survival (PFS). Results: High HALLMOUNT scores (≥2.5) were significantly associated with older age, comorbidities, poor ECOG status, isocitrate dehydrogenase (IDH)-wild phenotype, lower resection rates, and reduced treatment responses. ROC analysis showed predictive accuracy comparable to CAR and PIV (AUC = 0.650). High scores independently predicted inferior OS (HR = 2.78, p < 0.001) and PFS (HR = 2.76, p < 0.001). Conclusions: The HALLMOUNT score provides a simple, cost-effective, and biologically grounded biomarker reflecting both tumor aggressiveness and host vulnerability. It enables refined risk stratification, supports individualized therapeutic planning, and warrants prospective validation in molecularly defined and multicenter cohorts. Full article

Background: Systemic inflammation and nutritional status have emerged as promising prognostic indicators across various malignancies; however, their clinical relevance in advanced laryngeal cancer remains underexplored. This study aimed to evaluate the prognostic significance of inflammation- and nutrition-based indices on the overall survival (OS) and progression-free survival (PFS) in patients with locally advanced or metastatic laryngeal cancer. Methods: A total of 147 patients treated at Pamukkale University between 2013 and 2022 were retrospectively analyzed. Baseline hematologic and biochemical parameters were used to calculate the Naples Prognostic Score (NPS), the Controlling Nutritional Status (CONUT) score, the Systemic Immune–Inflammation Index (SII), the Systemic Inflammation Response Index (SIRI), the C-reactive Protein/Albumin Ratio (CAR), and the Prognostic Nutritional Index (PNI). Survival outcomes were estimated using the Kaplan–Meier method, and independent prognostic factors were identified by Cox regression analyses. Results: The median OS and PFS were 55.5 and 48.8 months, respectively. In univariate analyses, high NPS, CONUT, SIRI, SII, and CAR values were significantly associated with inferior OS and PFS (p < 0.05). Multivariate analyses identified advanced stage, disease progression during chemotherapy, and high NPS as independent predictors of both the OS and PFS, whereas surgery conferred a survival advantage. Conclusions: Inflammation- and nutrition-based indices, particularly NPS, are strong prognostic markers for survival in patients with advanced laryngeal cancer. Routine integration of these parameters may enhance individualized risk stratification and guide treatment decisions in clinical practice. Full article

Background/Objectives: The COVID-19 pandemic disrupted healthcare delivery worldwide, potentially delaying the diagnosis and treatment of oncologic diseases. This study aimed to evaluate the impact of the pandemic on stage at diagnosis, treatment allocation, and survival outcomes among patients with gastric cancer. Methods: We retrospectively analyzed 419 consecutive patients diagnosed with gastric cancer between January 2018 and December 2021 at a tertiary oncology–surgical center. Patients were divided into pre-pandemic (2018–2019) and pandemic (2020–2021) cohorts. Demographic, clinical, and treatment variables were compared using t-tests and χ² tests. Multivariate logistics and Cox regression models were applied to identify independent predictors of metastatic presentation and mortality. Overall survival (OS) was calculated from diagnosis to death or last contact (OS_days), with same-day events censored at time zero. Results: Baseline characteristics were comparable between cohorts (age, p = 0.098; sex, p = 0.137; residence, p = 0.345). The proportion of metastatic cases (M1) increased from 42.8% in 2018–2019 to 64.4% in 2020–2021 (χ² p < 0.001). Surgical rates remained stable (55.1% vs. 47.7%, p = 0.161). Diagnosis during the pandemic independently predicted metastatic presentation (OR = 2.63, 95% CI 1.68–4.11, p < 0.001) and higher mortality (HR = 1.72, 95% CI 1.41–2.03, p < 0.001). Kaplan–Meier analysis confirmed significantly reduced OS in the pandemic cohort (log-rank χ² = 81.29, p < 0.001). Conclusions: The pandemic was associated with delayed diagnosis, stage migration toward advanced disease, and inferior survival in gastric cancer, despite comparable demographics and treatment capacity. These findings emphasize the need to safeguard diagnostic pathways—particularly endoscopy—during healthcare crises to prevent avoidable oncologic deterioration. Full article

Background: The benefit of adjuvant chemotherapy for low-risk, mismatch repair proficient (pMMR) stage IIA colon cancer is uncertain. Surveillance is standard, but some patients relapse. Tegafur-uracil (UFT) is a low-toxicity oral option that may offer benefit; Methods: This retrospective study included patients with resected low-risk, pMMR stage IIA colon cancer (2013–2022). Patients receiving ≥5 postoperative UFT prescriptions were compared with those under surveillance. Propensity score matching (1:1) was applied, and disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox models with sensitivity analyses.; Results: Among 279 eligible patients, 71 matched pairs were analyzed. UFT reduced the risk of recurrence or death by 57% (DFS HR = 0.43, 95% CI 0.25–0.75, p = 0.002) and mortality by 62% (OS HR = 0.38, 95% CI 0.21–0.68, p < 0.001); Conclusions: UFT improved DFS and OS in low-risk pMMR stage IIA colon cancer, suggesting surveillance alone may undertreat some patients. Prospective trials are warranted. Full article