Search Results (51,138)

Microbacterium species, a genus of aerobic Gram-positive coryneform rods, are rare causes of human infection with only a few sporadic cases reported worldwide. MALDI-TOF MS, 16S rRNA gene sequencing, and even whole-genome sequencing are used to identify the species in a clinical laboratory setting. The study reports a case of Microbacterium paraoxydans bloodstream infection and reviews the literature, including eight additional reported cases of M. paraoxydans infection. We summarize the characteristics of each case, highlight the identification methods, and identify recurrent characteristics for M. paraoxydans infection. A 65-year-old man presented with stable condition of esophageal cancer and long-term prednisolone therapy for psoriasis. A central venous catheter (CVC) was placed for years for treatment of esophageal cancer. The patient presented with fever and chills, and Microbacterium paraoxydans was identified by MALDI-TOF MS from blood culture samples via chemo port. After the chemo port was removed, vancomycin followed by levofloxacin was administered for the entire 14-day treatment course according to susceptibility tests. This study highlights that a long-term central venous catheter and immunocompromised status were common characteristics among the reported cases of Microbacterium spp. infection. The susceptibility of Microbacterium spp. is not fully characterized and varies across reports; gentamicin and trimethoprim/sulfamethoxazole appeared more consistently active, whereas susceptibility to vancomycin was variable. We report this case to highlight the increasing number of infections caused by Microbacterium spp. in the current era and to provide information on the treatment of M. paraoxydans. Full article

Post-recurrence survival (PRS) after hepatectomy for hepatocellular carcinoma (HCC) varies widely, yet the prognostic significance of the recurrence pattern and time to recurrence (TTR) for PRS remains incompletely defined. This single-center retrospective study included 126 patients with first HCC recurrence after curative hepatectomy (2018–2024) and aimed to explore the prognostic role of recurrence pattern, classified as low-risk (oligo-recurrence: ≤3 intrahepatic nodules, each ≤3 cm) or high-risk (multiple/large intrahepatic, tumor in vein, or extrahepatic), for PRS. In the overall cohort, the recurrence pattern independently predicted PRS (hazard ratio 2.13, p = 0.015); the preoperative Barcelona Clinic Liver Cancer (BCLC) stage, gamma-glutamyl transferase, and total bilirubin were also independent predictors. A sensitivity analysis, including post-recurrence treatment, attenuated the hazard ratio for high-risk pattern to 1.82 (95% CI 0.93–3.55, p = 0.079), consistent with partial mediation. Kaplan–Meier analyses suggested an association between shorter TTR and worse overall survival (OS), but this finding is descriptive because OS measured from surgery is mathematically coupled with TTR. In an exploratory subgroup analysis of patients with early-stage primary HCC (BCLC 0/A, n = 98), the recurrence pattern showed a borderline association with PRS (p = 0.053). Late detection was associated with high-risk recurrence but did not independently affect survival. These findings highlight the prognostic value of the recurrence pattern for PRS and support the consideration of TTR as a descriptive prognostic indicator, which together may inform risk-adapted follow-up and treatment strategies. Full article

Background/Objectives: We aimed to evaluate the temporal associations and heterogeneous patterns between the Beijing Diagnosis-Related Group (DRG) 2.0 payment reform and hospitalization costs and resource utilization among patients receiving major colorectal cancer (CRC) surgery and to explore hospital adaptive cost adjustment behaviors under bundled payment constraints. Methods: Utilizing inpatient data of 1232 colorectal cancer surgical patients from a Beijing hospital spanning January 2021 to October 2024, we adopted segmented regression interrupted time-series analysis (ITSA), with April 2022 defined as the policy intervention point. The analysis used total hospitalization expenses, itemized costs, cost composition proportions, and length of stay (LOS) as outcome indicators, conducted heterogeneity analysis, and applied seasonal autoregressive integrated moving average (SARIMA) counterfactual forecasting as a supplementary sensitivity check. All medical expenditures were inflation-adjusted based on Beijing’s medical consumer price index (CPI), with 2024 as the base year. Results: After DRG implementation, total hospitalization costs showed an immediate decrease of 13,111.73 CNY and a sustained monthly downward trend of 1312.60 CNY. Medical consumable fees were the main component associated with total-cost reduction, and their proportion declined immediately by 4.1 percentage points. LOS showed no abrupt immediate decline but shortened by 0.22 days per month over the post-reform period. Heterogeneous association patterns were observed across selected clinical and treatment subgroups. SARIMA counterfactual forecasting provided supplementary, directional sensitivity evidence for the primary outcomes and was interpreted cautiously for volatile sub-item expenditures. Conclusions: DRG 2.0 reform was associated with lower hospitalization costs and improved bed-turnover efficiency among CRC surgical patients, mainly through reductions in consumable expenditures. Full article

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and liver metastasis remains a major contributor to poor prognosis and treatment failure. Increasing evidence indicates that the gut–liver axis plays a critical role in colorectal cancer liver metastasis (CRLM) by linking intestinal microbial alterations with hepatic microenvironmental remodeling. Gut dysbiosis and intestinal barrier disruption facilitate the translocation of microbial components and metabolites through the portal circulation, contributing to hepatic immune remodeling, extracellular matrix alteration, and the establishment of a pre-metastatic niche favorable for tumor colonization. During metastatic progression, specific tumor-associated microorganisms may further promote circulating tumor cell (CTC) survival, immune evasion, and metastatic adaptation, while intratumoral microbiome alterations and metabolic reprogramming may influence tumor growth and therapeutic responses. This review summarizes the current understanding of gut–liver axis-mediated regulation of CRLM, focusing on intestinal barrier dysfunction, microbial translocation, hepatic pre-metastatic niche formation, tumor cell–microbiota interactions, and emerging clinical applications. Unlike previous reviews that have primarily focused on gut microbiota alterations in colorectal carcinogenesis, this review emphasizes the contribution of gut-derived microbial signals to liver-specific metastatic evolution. In addition, we discuss current challenges, including limited human causal evidence, technical issues in low-biomass microbiome analysis, and the need for longitudinal clinical validation. Future integration of spatial multiomics, prospective cohorts, and personalized microbiome-based interventions may provide new opportunities for early risk prediction and precision management of CRLM. Full article

Antimicrobial resistance is a growing global crisis that threatens to return humanity to a pre-antibiotic era where common infections become deadly. This narrative review synthesizes evidence from 2000 to early 2026, including Global Research on Antimicrobial Resistance data and World Health Organization surveillance, to outline the problem’s scale, drivers, and solutions. In 2019, bacterial resistance directly caused 1.27 million deaths and was linked to 4.95 million more. Low- and middle-income countries bear the heaviest burden. ESKAPE pathogens, especially carbapenem-resistant Acinetobacter baumannii and NDM-producing Klebsiella pneumoniae, drive intensive care unit mortality near 50% and cause untreatable neonatal sepsis. One Health drivers include antibiotic overuse in humans, with 30% of prescriptions unnecessary in high-income settings; agriculture, consuming 70% of global antibiotics; and environmental pollution, with resistance genes found in 72% of rivers. Bacteria spread resistance through horizontal gene transfer and mutations such as gyrA S83L, creating pan-drug-resistant strains that make surgeries, transplants, and cancer treatment risky. Economic modeling studies suggest that unchecked antimicrobial resistance could reduce annual global GDP by 1.1–3.8%, with some scenarios projecting losses of up to approximately 5% by 2050, depending on assumptions about healthcare costs, labor productivity, and livestock production. Solutions require subscription-based payment models, enforceable agricultural regulations, integrated genomic surveillance, and equity-focused diagnostics for low- and middle-income countries. Without binding 2030 targets, the post-antibiotic era would become a clinical reality within a decade. Full article

Poly(ADP-ribose) polymerase inhibitors (PARPis) have transformed the treatment landscape of homologous recombination-deficient malignancies, particularly BRCA1/2-mutant breast, ovarian, pancreatic, and prostate cancers. In contrast, clinical studies evaluating PARPis in broadly selected colorectal cancer (CRC) patients have yielded disappointing outcomes despite evidence that a subset of CRCs harbor DNA damage response (DDR) defects and homologous recombination deficiency (HRD)-associated mutational signatures. These observations highlight the need for improved patient stratification and the development of strategies to enhance PARPi sensitivity in CRC. In this review, we integrate CRC-specific evidence with mechanistic and preclinical findings from other malignancies and discuss candidate biomarkers associated with PARPi responsiveness, including TP53, RAD51, and MRE11, and examine their potential utility in identifying CRC patient populations most likely to benefit from PARP inhibition. We further summarize therapeutic approaches aimed at inducing “BRCAness” and sensitizing CRC cells to PARPis through epigenetic modulation, targeting cell-cycle checkpoint regulators, inhibiting growth factor signaling pathways, and exploiting metabolic vulnerabilities. Emerging strategies involving polyamine inhibition and modulation of NAD+ metabolism have been specifically highlighted for their potential role in therapeutic response. Collectively, these approaches provide a framework for investigating mechanistically compelling opportunities to overcome intrinsic and acquired resistance to PARPis and expand the clinical utility of DDR-targeted therapies in CRC. A deeper mechanistic understanding of PARPi response and resistance, in addition to extensive investigations in CRC-specific models and molecularly selected clinical cohorts, will facilitate the development of biomarker-driven combination therapies and improve outcomes for patients with CRC. Full article

Neuroblastoma is among the most aggressive pediatric cancers, and resistance to standard therapies highlights the need for alternative strategies targeting lipid metabolism and apoptosis-associated pathways. This study aimed to investigate the cytotoxic and apoptotic effects of fingolimod, ceranib-2, and carmofur, administered individually and in combination, in SH-SY5Y neuroblastoma cells, with particular emphasis on ceramide metabolism. Cytotoxicity was evaluated using the MTT assay, and morphological alterations were assessed by confocal microscopy. Colony-forming ability was examined using a soft agar assay, apoptosis-associated responses were evaluated by Annexin-V staining and caspase 3/7 activation analysis, and intracellular ceramide levels were determined using an ELISA-based method. The results showed that all three compounds reduced cell viability in a concentration-dependent manner and decreased clonogenic survival. The triple combination produced the most pronounced changes in apoptosis-associated parameters and showed marked inhibition of colony formation, although fingolimod alone exhibited the lowest IC₅₀ value and therefore remained the most potent treatment on an IC₅₀ basis. Confocal microscopy revealed prominent apoptosis-associated morphological alterations, including chromatin condensation, nuclear fragmentation, and cytoskeletal disruption, particularly in the triple-combination group. Annexin-V and caspase 3/7 analyses showed increased apoptotic cell populations, with the highest levels observed following triple-combination treatment. Intracellular ceramide levels were also significantly elevated, particularly in cells treated with ceranib-2 and the triple combination. Collectively, these findings indicate that simultaneous modulation of ceramide- and S1P-associated pathways influences apoptosis-associated responses, clonogenic growth, and intracellular ceramide levels in SH-SY5Y cells. However, because the study was conducted in a single neuroblastoma cell line and did not include comprehensive dose-by-time or formal combination-interaction analyses, the findings should be regarded as preliminary in vitro observations. Further validation in genetically distinct neuroblastoma models, together with systematic dose–response and time–response studies, will be required to determine the reproducibility, biological significance, and broader therapeutic relevance of this approach. Full article

Background/Objectives: To evaluate the concordance of dual-layer spectral CT (DLSCT) with MRI in locoregional staging of rectal cancer, focusing on 40 keV virtual monoenergetic reconstructions. Methods: This retrospective single-center study included 31 patients (mean age, 69 ± 13.3 years) with rectal cancer who underwent both MRI and DLSCT within 30 days before treatment. Venous-phase CT images were reconstructed at 40 keV. Assessed parameters included tumor location, longitudinal extent, distance from the anorectal junction and anal verge, mesorectal infiltration, circumferential resection margin (CRM) involvement, suspicious lymph nodes, extramural vascular invasion (EMVI), desmoplastic reaction, peritoneal involvement, and anal canal invasion. Two radiologists performed consensus readings. Paired continuous measurements were compared with the Wilcoxon signed-rank test. Agreement for categorical variables was evaluated using Cohen’s kappa; sensitivity, specificity, and accuracy were calculated using MRI as the imaging reference standard. Results: No significant differences were found between MRI and DLSCT for the continuous measurements evaluated. Complete agreement was observed for CRM involvement, anal canal invasion, peritoneal involvement, desmoplastic reaction, and suspicious lymph-node classification (accuracy, 100%; κ = 1.00). Agreement was almost perfect for mesorectal infiltration (κ = 0.84). For EMVI, DLSCT reproduced all MRI-positive classifications but generated two additional positive findings, resulting in 100% sensitivity, 71.4% specificity, 93.5% accuracy, and substantial agreement (κ = 0.79). Conclusions: DLSCT showed high concordance with MRI for several locoregional imaging features of rectal cancer. It may provide complementary information, particularly when MRI is contraindicated or inconclusive. In addition, when DLSCT is performed for systemic staging, it has the potential to provide both locoregional and distant disease assessment within a single examination. However, these findings do not establish equivalence to MRI or diagnostic accuracy against histopathology, and further prospective studies with pathological correlation are warranted. Full article

Plasma metabolomics offers a promising avenue for the non-invasive classification of lung cancer. However, most classification frameworks treat lung cancer as a single entity, conflating non-small-cell lung cancer (NSCLC) with pulmonary neuroendocrine neoplasms (NENs), despite their distinct biology and treatment pathways. We apply a heterogeneous graph neural network to a three-class problem discriminating Control, NSCLC, and NEN from targeted plasma metabolomic profiling in 800 participants (466 NSCLC, 120 NEN, 214 Controls). Matched metabolites were annotated by Cell Danger Response (CDR) relevance class and expected direction of change, with these annotations encoded as metabolite features and direction-aware patient–metabolite edge weights. Across ten random seeds, the three-class model achieved a macro-F1 of $0.898\pm 0.026$ and macro-AUROC of $0.962\pm 0.016$. Collapsing the three-class posteriors to a cancer-versus-control score yielded an AUROC of $0.951\pm 0.017$, a sensitivity of $0.960\pm 0.011$, and an F1 score of $0.949\pm 0.010$. A separate cancer-only classifier distinguished NEN from NSCLC with an accuracy of $0.960\pm 0.026$ and an AUROC of $0.985\pm 0.020$. The gradient-times-input attribution identified one-carbon, glycine–serine, proline, and ornithine–arginine metabolic programs, with proline, C5DC, uric acid, and fumaric acid among the leading annotated metabolites. Removal of all 11 cohort-derived Class N annotations left NSCLC-versus-NEN AUROC essentially unchanged, and broader comparator analyses showed no measurable predictive advantage of the CDR prior over the otherwise matched concentration-weighted GNN. These findings indicate that predictive discrimination is driven primarily by the measured metabolomic features, whereas the CDR component provides a biologically structured framework for directional metabolite and pathway interpretation. Independent external and prospective validation is required to establish generalizability and clinical utility. Full article

Lymphedema is usually approached as a survivorship complication; yet, many of the injuries that produce lymphatic failure begin during cancer treatment planning. Regional nodal irradiation, chemoradiation, lymph-node surgery, systemic therapy, obesity, infection history, and baseline lymphatic reserve can converge to produce chronic swelling, fibrosis, cellulitis risk, functional limitation, and an impaired quality of life. Despite this, lymphatic drainage pathways are rarely contoured, constrained, or prospectively monitored as organs at risk in radiotherapy practice. This commentary argues that the lymphatic system should enter radiotherapy-planning discussions as a candidate toxicity structure, while cautioning against premature universal dose constraints. Evidence signals are clinically meaningful but not yet protocol-defining: in the MA.20 breast cancer trial, regional nodal irradiation increased lymphedema from 4.5% to 8.4%; in nasopharyngeal carcinoma, mean doses of approximately 58.7 Gy to level IV and 58.6 Gy to levels I–VII were proposed as thresholds associated with moderate/severe facial lymphedema; and gynecological cancer studies report wide lower-limb lymphedema incidence ranges, with radiotherapy, lymphadenectomy, number of nodes removed, and body mass index repeatedly implicated as risk factors. The immediate priority is not mandatory lymphatic sparing, but lymphatic-aware planning: a baseline risk assessment, reproducible candidate contours, dose–volume reporting, selective sparing where oncologically safe, and prospective toxicity monitoring. The author proposed a framework to reflect this argument. Making lymphatic toxicity visible, measurable, and modelled may help shift lymphedema from an accepted late effect to a potentially preventable planning endpoint. Full article

The kidney is an essential organ that has a crucial role in preserving homeostasis within the human body. Kidney cancer is considered a major clinical challenge owing to its resistance to traditional treatments such as chemotherapy, radiotherapy, and immunotherapy. Nanoparticles (NPs) gain great attention in cancer therapy due to their low toxicity, biocompatibility, and targeted drug delivery capability. This review focuses on the current role of green-synthesized NPs in renal cell carcinoma management and their applications in targeted drug delivery and cancer-specific targeting mechanisms with the demonstration of the environmentally friendly green synthesis approaches utilizing biological resources such as plant extracts and microorganisms, highlighting their advantages over conventional synthesis methods in terms of biocompatibility, sustainability, and reduced toxicity. Moreover, the therapeutic potential of nanomaterials is discussed, including magnetic NP-mediated thermal therapy, photothermal therapy, gene delivery systems, and RNA interference-based strategies. We underscore the challenges and limitations of NPs, including in vivo toxicity, biodistribution, clinical translation, large-scale production, batch-to-batch variability, long-term safety, scalability, repeatability, regulation, and reproducibility. There is growing potential to improve the treatment of kidney cancer. Hence, the promising prospects of nanotechnology in kidney cancer treatment provide a foundation for future research and clinical application. This comprehensive article highlights the significant contributions of nanomedicine to oncology and shows an optimistic perspective for more effective and precise treatment strategies for kidney cancer. Full article

The war in Ukraine, beginning in February 2022, disrupted continuous medical care for Ukrainian childhood and adolescent cancer patients (UCC), many of whom were relocated to pediatric cancer centers worldwide, including Switzerland. In this Brief Report, we describe their health-related quality of life (HRQoL) after arrival. In a multicenter, cross-sectional survey across five Swiss pediatric oncology centers, we included patients ≤18 years at diagnosis who arrived after 24 February 2022 and were undergoing active treatment. HRQoL was assessed by the PedsQL™ 4.0 Generic Core Scales (self- and parent-reports). Fourteen of 23 eligible families (61%) participated. HRQoL declined with age, particularly in physical functioning, while psychosocial functioning remained relatively stable but lower among adolescents; parent scores closely matched self-reports. Scores were referenced against a published cohort of healthy Ukrainian children and previously reported pediatric cancer populations. Given the small sample and lack of a matched control group, the findings cannot separate the effects of displacement, cancer, and treatment and are hypothesis-generating. They suggest a potential role for age-tailored supportive care in displaced children with cancer and call for larger, controlled studies. Full article

As of 2020, liver cancer has emerged as the fifth most common cancer and the third leading cause of cancer death worldwide, following lung and colorectal cancers. The most prevalent type is hepatocellular carcinoma (HCC), originating from hepatocytes. Despite advancements, liver cancer treatment outcomes remain poor due to metastasis and recurrence. Existing anticancer drugs often exhibit narrow therapeutic windows and limited selectivity for cancer cells. Manilkara zapota (L.) P. Royen has attracted significant scientific attention because of its diverse bioactive constituents and potential therapeutic properties. Of particular interest in this review, we explored the molecular connectivity of oxidative stress-induced liver cancer. We discussed the underlying mechanisms of Manilkara zapota (L.) P. Royen involved in cancer and inflammation. The phytochemical constituents were also highlighted in this study. The phytochemicals reported from Manilkara zapota (L.) P. Royen included flavonoids, tannins, saponins, and phenolic compounds. These compounds demonstrated potential anticancer activities through mechanisms such as induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and regulation of PI3K/Akt and NF-κB signaling pathways. Further investigations are required to clarify the benefit–risk profile of Manilkara zapota (L.) P. Royen through large-scale clinical trials. Collectively, the current evidence suggests that this plant may offer a promising strategy for cancer management, provided that such interventions are optimized to minimize adverse effects. Full article

Background: Racial and socioeconomic differences in prostate cancer outcomes are often described as survival disparities, but observed differences may also reflect healthcare access, treatment delivery, and resource allocation. Methods: NCDB and SEER–Medicare were treated as independent, complementary retrospective data sources without individual-level linkage. The analytic material comprised 111,396 database records from 2010 to 2020 across two independent source files; this is a cross-source record count, not a deduplicated count of unique persons. Harmonized descriptive analyses characterized stage, treatment, and treatment timing, while multivariable Cox proportional hazards modeling evaluated prostate cancer-specific survival (CSS) in outcome-eligible SEER–Medicare records. The CSS model denominator is therefore substantially smaller than the total record count, and the two should not be confused. Results: Records for non-Hispanic Black (NHB) men more often showed stage III–IV disease than records for non-Hispanic White (NHW) men (26.9% vs. 18.7%) and lower receipt of guideline-concordant first-course management initiated within 90 days, particularly in the low-SES subgroup (51.4% vs. 84.3% among high-SES NHW men). In the adjusted CSS model, NHB race was associated with higher mortality (HR = 1.32; 95% CI: 1.24–1.41). Uninsured status (HR = 1.47; 95% CI: 1.33–1.62), low income (HR = 1.28; 95% CI: 1.19–1.37), and rural residence (HR = 1.14; 95% CI: 1.06–1.22) were also associated with higher mortality. Conclusions: The findings support a healthcare-system interpretation of prostate cancer disparities and identify measurable targets for prospective evaluation, including EHR-enabled monitoring, nurse navigation, telehealth-supported follow-up, and facility-level treatment-concordance review. Full article