BACKGROUND: Stereotactic ablative radiotherapy (SABR) is emerging as an alternative treatment for patients with locally recurrent prostate cancer after previous radiation. This approach allows for precise target coverage while limiting toxicity to surrounding organs. However, reported outcomes following re-irradiation of the prostate with SABR remain variable. This systematic review and meta-analysis therefore evaluated the efficacy and toxicity of prostate re-irradiation with SABR. METHODS: A systematic review and meta-analysis compliant with PRISMA guidelines was conducted to evaluate studies of SABR for local re-irradiation of prostate cancer. Random-effects models were employed to pool biochemical recurrence-free survival (BRFS), local relapse-free survival (LRFS), metastasis-free survival (MFS), and gastrointestinal (GI) and genitourinary (GU) toxicities after SABR re-irradiation. Outcomes were pooled as proportions using the Freeman-Tukey double arcsine transformation, and heterogeneity was assessed using I. Statistical analyses were performed using Stata version 19.5. RESULTS: A total of 30 treatment cohorts from 29 studies, including 1099 patients, were analysed. The pooled rates for 2-year BRFS, LRFS, and MFS were 62.5% (95% CI, 54.1-70.6%; I = 81.9%), 89.9% (95% CI, 80.6-96.5%; I = 85.5%), and 84.6% (95% CI, 77.3-90.7%; I = 77.8%), respectively. Acute severe side effects were rare, with pooled rates of grade 3-4 GI toxicities of 0.7% (95% CI, 0.3-1.4%; I = 0%) and grade 3-4 GU toxicities of 1.1% (95% CI, 0.6%-1.9%; I = 0%). Late grade 3-4 toxicity also remained low, with pooled GI and GU rates of 1.0% (95% CI, 0.5-1.7%; I = 0%) and 3.3% (95% CI, 2.0-5.0%; I = 46.1%), respectively. CONCLUSION: Prostate re-irradiation with SABR is associated with favourable short- and intermediate-term oncologic outcomes, including high local control and metastasis-free survival, with acceptable toxicity. The heterogeneity observed across studies and the very low certainty of evidence encourage the inclusion of these patients in prospective trials or registries to improve patient selection, dose-fractionation strategies, and long-term outcomes.

Thyroid cancer (THCA) is the most common endocrine malignancy worldwide, understanding the pathophysiological mechanism is vital for developing effective strategies for prevention, diagnosis, and treatment. In this study, paired tumor and adjacent noncancerous tissues were collected from THCA patients. Cell viability and proliferation were assessed using CCK-8 and EdU assays. Cell migration and invasion were evaluated by wound healing and Transwell assays. Co-immunoprecipitation was performed to examine RNF123-mediated KAT5 ubiquitination, and chromatin immunoprecipitation was used to assess KAT5 enrichment at the PSPC1 promoter. An experimental lung metastasis model was established to evaluate the effects of RNF123 overexpression on tumor growth and pulmonary metastasis. RNF123 was down-regulated in THCA tissues and cell lines, and its overexpression suppressed cell viability, proliferation, migration, and invasion. KAT5 and PSPC1 were up-regulated in THCA cells. KAT5 knockdown inhibited THCA malignant behaviors. Mechanistically, RNF123 promoted the ubiquitination and degradation of KAT5, thereby reducing KAT5-mediated histone acetylation at the PSPC1 promoter and subsequent IGF1R up-regulation. In conclusion, RNF123 inhibited THCA malignant phenotype by promoting KAT5 ubiquitination and degradation, which reduced KAT5-mediated histone acetylation at the PSPC1 promoter, thereby down-regulating PSPC1 and IGF1R expressions.

BACKGROUND: Radiotherapy is established as a standard treatment for low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its prognostic impact for high-volume mHSPC under upfront therapy is unclear. This study investigates the effect of adding prostate-directed radiotherapy (PDRT) with or without metastasis-directed radiotherapy (MDRT) to upfront doublet therapy for high-volume mHSPC. METHODS: We retrospectively assessed 239 patients who received upfront doublet therapy for synchronous high-volume mHSPC between 2018 and 2025. Patients were divided into a PDRT (with or without MDRT; n = 32) and a non-PDRT group (n = 207). The primary endpoint was castration resistance-free survival (CRFS). RESULTS: The median time from treatment initiation for mHSPC to PDRT initiation was 7.0 months. We excluded 31 patients from the non-PDRT group who progressed to castration-resistant prostate cancer within 7.0 months. Our 7-month landmark analysis found significantly prolonged CRFS in the PDRT group compared with the non-PDRT group in a propensity score-matched cohort (hazard ratio [HR] 0.47, 95% CI: 0.23-0.97, p = 0.045). An interaction analysis demonstrated that the effect of MDRT differed according to PDRT status (HR 0.37, 95% CI: 0.22-0.57, p = 0.008). The prolonged survival in the PDRT group remained significant in a time-dependent multivariable Cox analysis (HR 0.47, 95% CI: 0.22-0.88, p = 0.021). CONCLUSIONS: We found significantly prolonged CRFS in the PDRT group compared with the non-PDRT group among patients receiving upfront doublet therapy for high-volume mHSPC. Interaction analysis also suggested that the effect of MDRT may differ according to PDRT status; however, these findings should be regarded as hypothesis-generating. Further large prospective studies are needed to validate these findings in patients with high-volume mHSPC.

Innovative synthetic methods that allow for the direct, efficient modification of complex lead compounds are essential for accelerating drug development. In particular, molecular editing enables the precise, late-stage diversification of privileged scaffolds, streamlining the drug optimization process. This review systematically evaluates the rapidly expanding repertoire of molecular editing, predominantly focusing on editing natural products and drug molecules. We classify these strategies into skeletal and peripheral editing, assembling recent representative cases that illustrate their utility in direct editing of complex molecules. Complementing these chemical approaches, biomimetic molecular editing (also called nature-inspired molecular editing) is briefly discussed. By highlighting strategies that enable the site-selective diversification of complex scaffolds, this review seeks to guide future efforts in the direct late-stage editing of natural products and drug molecules.

Emerging evidence highlights the critical role of circular RNAs (circRNAs) in regulating pathological processes in various diseases, including organ fibrosis. Endometrial fibrosis, commonly referred to as intrauterine adhesions (IUA), is a major cause of uterine infertility. However, the involvement of circRNAs in the pathogenesis of IUA remains largely unexplored, necessitating further research. This study aimed to identify a specific circRNA that may serve as a diagnostic biomarker and therapeutic target for IUA. CircRNA microarray analysis was performed to compare circRNA expression profiles between paired fibrotic and normal endometrial samples from patients with IUA. The expression of hsa_circ_0079474 was significantly upregulated in fibrotic tissues compared with normal tissues. Functional analyses demonstrated that hsa_circ_0079474 enhanced cell proliferation, promoted cell cycle progression, and facilitated epithelial-mesenchymal transition (EMT) in vitro, as assessed by qRT-PCR, CCK-8 assays, EdU assays, flow cytometry, and Masson staining. Mechanistically, dual-luciferase reporter assays and RNA immunoprecipitation confirmed that hsa_circ_0079474 acted as a molecular sponge for miR-630, leading to the upregulation of YAP1. In an IUA rat model, hsa_circ_0079474 was found to drive EMT, whereas miR-630 administration reversed this process and ameliorated endometrial fibrosis. Consequently, these findings indicate that hsa_circ_0079474 contributes to the progression of IUA by modulating the miR-630/YAP1 axis, providing new insights into circRNA-mediated mechanisms in IUA and highlighting hsa_circ_0079474 as a potential therapeutic target.

Pyrimidine has become an important scaffold for designing anticancer drugs because of its planar aromatic structure, synthetic versatility, and ability to establish key interactions with its target. This heterocyclic scaffold is an essential component of nucleic acids and many biologically active molecules, which makes it highly relevant for therapeutic application. In recent years, significant attention has been directed toward pyrimidine-based hybrid molecules, in which the pyrimidine core is integrated with other bioactive scaffolds to enhance the anticancer activity. The present review encompasses a wide range of such hybrids, including pyrimidine-quinoline, pyrimidine-indole, pyrimidine-triazole, pyrimidine-chalcone, pyrimidine-pyrazole, pyrimidine-imidazole, pyrimidine-thiazole, and pyrimidine-oxadiazole derivatives. This hybridization strategy facilitates the development of multitargeted agents capable of modulating key signaling pathways in cancer. Among these, epidermal growth factor receptor (EGFR) has gained particular importance due to its central role in tumor growth, survival, and metastasis. This review focuses on the last 2 years' advancements (from Jan 2025 to early 2026) in the development of pyrimidine-containing hybrid molecules as EGFR inhibitors. Different hybridization techniques involving pyrimidine linked or fused with another moiety are comprehensively discussed. Furthermore, the present review summarizes the structure-activity relationship (SAR), mechanistic pathway, and molecular interactions responsible for their anticancer potential, with a specific emphasis on their EGFR inhibitory activity, including effects on mutant EGFR. Notably, compounds 16a and 16b (pyrazolo[3,4-d]pyrimidine-sulfonamide hybrids) were identified as the most active EGFR inhibitors with IC of 0.069 and 0.064 µM, respectively. Additionally, pyrimidine-based anticancer agents under clinical investigation as EGFR inhibitors are briefly highlighted. Overall, pyrimidine-based hybrids represent a promising direction as next-generation anticancer therapeutics.

Prognostic factors for long-term survival (LTS), defined as overall survival (OS) of ≥10 years, remain uncertain among patients with myeloma who undergo autologous stem cell transplantation (ASCT). We retrospectively analyzed 3650 patients with myeloma who underwent ASCT between 1994 and 2013 using the Japanese Society of Transplantation and Cellular Therapy registry. The proportion of long-term survivors was 28.7%. In logistic regression analyses, IgG-type, absence of high-risk cytogenetic abnormality (HRCA), International Staging System (ISS) I/II, and post-transplantation therapy were associated with LTS. Cox regression analysis revealed that kappa light chain type and post-transplantation therapy predicted better OS, whereas PS 2-4, HRCA, melphalan dose under 200 mg/m, and ISS III predicted a shorter OS. We classified patients into three groups on the six significant factors; the estimated 10-year OS among the favorable group was 60.9%. ISS, HRCA, M-protein subtype, melphalan dose, achieving CR, and post-transplantation therapy were associated with LTS after ASCT.

Extramedullary hematopoiesis is reactive or clonal trilineage hematopoiesis presenting outside the bone marrow, and it is typically caused by an underlying neoplastic process. In this report, we present the case of a 58-year-old patient who underwent multiple kidney transplantations. Follow-up imaging revealed a tumour-like mass in the soft tissue near the graft kidney. Biopsy revealed extramedullary hematopoiesis without dysplastic features or blast increase. The patient did not show blood count abnormalities suggestive of bone marrow disease. From a prognostic and therapeutic point of view, the most important is to distinguish extramedullary hematopoiesis from myeloid sarcoma. In myeloid sarcoma, the proportion of myeloid blasts exceeds 20%, and the condition is essentially equivalent to acute myeloid leukemia, requiring appropriate treatment. Extramedullary hematopoiesis, as in the presented case, may be asymptomatic. In this instance, follow-up is recommended. In symptomatic cases however, drug treatment or radiation therapy may also be applied. Orv Hetil. 2026; 167(34): 1365-1369.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising light-induced approaches for cancer treatment. This article outlines the historical development of PDT and summarizes the underlying photophysical and photochemical mechanisms responsible for reactive oxygen species (ROS) generation and tumour destruction. Major classes of clinically approved and emerging photosensitizers (PSs) are discussed together with important design criteria and current limitations. In addition, the principles of PTT, including its oxygen-independent mechanism and major classes of photothermal agents (PTAs), are presented. Finally, current challenges and future perspectives regarding selectivity, tissue penetration, biocompatibility, and clinical translation of light-induced therapies are highlighted.

Kinase inhibitors are a cornerstone of modern drug discovery, with more than 100 approved compounds which have had a transformative impact in precision oncology and inflammatory disease. Their success has rested largely on small-molecule control of catalytic activity through ATP-site engagement; a framework that leaves important biology unaddressed, including non-catalytic kinase functions, resistance driven by active-site mutation, and the limits of selectivity imposed by pocket conservation. Against this backdrop, the observation that kinase inhibitors can reduce target protein abundance has gained new mechanistic depth. Chaperone deprivation, supercharging of native degradation circuits, and context-dependent mutant-selective depletion mark distinct routes through which inhibitor binding can intersect with cellular proteostasis. The kinase inhibitor CR8 extends this logic into chemically encoded degradation: CR8 acts as a molecular glue degrader by creating, within the ligand-bound kinase complex, a composite surface that directly recruits a ubiquitin ligase, resulting in cyclin K degradation. Thalidomide analogues can degrade kinases through scaffolds that do not bind the kinase in isolation: ligase-binding compounds that recruit neosubstrate kinases through recognition of structural surface degrons. Deliberately engineered PROTACs encode ligase-target proximity through heterobifunctional architecture to convert kinase binders into degraders. Beyond degradation, induced-proximity mechanisms - from the clinically established rapamycin to bifunctional molecules that redirect kinase activity or restrict inhibition to tumour cells - show how small molecules can reshape kinase interaction states rather than simply block active sites. Together, these examples define an expanding pharmacological vocabulary for kinase drug discovery: one that asks not only whether a molecule inhibits its target kinase, but how ligand binding rewires protein stability, interactions, localisation, and function.

BACKGROUND: Locally recurrent rectal cancer (LRRC) occurs in 6-10% of patients after curative surgery. It is often regarded as a simple residual disease, yet accumulating evidence suggests that LRRC is biologically distinct from primary tumors. Clonal evolution in matched primary-recurrence pairs not exposed to preoperative therapy has not been systematically investigated. METHODS: We analyzed formalin-fixed paraffin-embedded tumor specimens from 15 matched pairs of primary and locally recurrent rectal cancers not exposed to preoperative therapy using targeted next-generation sequencing of 22 colorectal cancer-related genes, including TP53, KRAS, PIK3CA, MET, and FGFR family members. Tumor areas were selectively collected to ensure high tumor purity. Mutations were classified as shared or unique, and variant allele frequencies (VAFs) and clonality (VAF > 30%) were evaluated. RESULTS: Among 415 pathogenic mutations, 12/15 pairs (80%) harbored shared driver alterations, with TP53 shared in 11 (73%). Shared mutations showed higher VAFs in recurrences than in primaries (median 57.1% vs 47.6%; p = 0.003). Unique mutations were modestly higher in recurrences (median 5.4% vs 4.8%; p = 0.048). Clonal mutations exhibited greater VAFs at recurrence (median 86.4% vs 49.8%; p = 0.048), while the numbers of clonal mutations were comparable (32 vs 32). Potentially actionable alterations involving MET and FGFR family genes were observed in recurrent lesions in a subset of cases, including some detected at clonal levels. CONCLUSIONS: LRRC is not merely residual disease but an evolutionarily progressed tumor entity characterized by persistence and dominance of truncal drivers with acquisition of clinically relevant alterations. Profiling recurrent lesions may guide therapy as primary tumor profiling alone may miss potentially actionable alterations present in recurrent lesions.

Spinal cord tissue engineering scaffolds represent a highly promising option for the treatment and repair of spinal cord injury (SCI). They have a wide range of potential applications and, as essential biomaterial carriers, can restore the multifunctional microenvironment. Since spinal cord tissue engineering scaffolds have developed rapidly in recent years, a comprehensive and up-to-date review outlining future research directions and summarizing current findings is urgently needed. This paper first introduces the functional and fundamental material criteria for tissue engineering scaffolds used in the treatment of SCI. Next, we review developments in scaffold functionalization, including material modification and composites, scaffold structural design, cell seeding, and the delivery of bioactive molecules. We then provide an overview of design approaches for multifunctional composite scaffolds, such as synergistic composite scaffolds and smart responsive designs. Finally, we outline the current limitations of spinal cord tissue engineering scaffolds and their future development directions. We hope this article will provide valuable insights to support the application of spinal cord tissue engineering scaffolds in the biomedical field.

AIMS: To explore the trajectories of supportive care needs and identify influencing factors in lung cancer surgical patients. DESIGN: Prospective cohort study. METHODS: Data from 287 patients at a Chinese tertiary hospital were collected at admission (T0), 2 weeks post-surgery (T1), 3 months (T2), 6 months (T3) and 1 year post-surgery (T4). Latent class growth models were used to identify supportive care need trajectories, and logistic regression was used to analyse influencing factors. RESULTS: Three trajectories emerged: Sustained High Needs Group (C1, 10.8%), Moderate Gradual Declining Group (C2, 56.4%), High-Rapid Decline-Rebound Group (C3, 32.8%). Compared with C2, C1 membership was positively associated with no regular exercise, severe baseline symptoms, and adjuvant therapy; C3 membership was positively associated with segmentectomy, no regular exercise, and high social support but inversely associated with civil servant or professional status. CONCLUSION: Our study identified heterogeneity in the trajectories of supportive care needs among lung cancer surgery patients. Regular exercise, symptom burden, adjuvant therapy, segmentectomy, social support and occupation were associated with these trajectories. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses may incorporate dynamic, trajectory-informed assessment into postoperative follow-up. The associated factors identified in this study may provide practical cues for earlier recognition of patients who may benefit from closer monitoring and anticipatory supportive care planning. This approach may be particularly relevant for patients with factors associated with persistent high needs or late rebound trajectories. IMPACT: Provides longitudinal insights into the heterogeneous evolution of supportive care needs from preoperative to 1-year post-surgery. Identifies three distinct supportive care needs trajectory patterns and their associated sociodemographic and clinical factors. Offers practical cues for identifying patients who may benefit from closer follow-up and for informing dynamic, trajectory-informed supportive care planning. REPORTING METHOD: This study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: None.

BACKGROUND: Youth e-cigarette use is a public health concern, yet cessation approaches remain suboptimal. In adults, faster nicotine metabolism is linked with better cessation outcomes with varenicline compared to nicotine replacement therapy (NRT). This remains unexplored in youth, for whom NRT is first-line treatment. This study examined whether nicotine metabolism is associated with nicotine dependence among hospitalized youth aged 14-21 who currently use e-cigarettes. METHODS: This cross-sectional study assessed e-cigarette use, nicotine dependence, saliva nicotine metabolism ratio (NMR) (slow [1 quartile], normal [2-4 quartile]), and genetic variation. Activity score (AS) was used for genotype-predicted phenotype (slow metabolizers, AS ≤ 1.5, normal metabolizers, AS > 1.5). Analyses included Fisher's exact, Wilcoxon rank-sum, and logistic regression. RESULTS: Among 106 hospitalized youth (mean age 16 ± 1.3), 38% reported near-daily e-cigarette use and 50% had medium-to-high nicotine dependence. Dependence varied by e-cigarette use ( < 0.001) and nicotine metabolism ( = 0.027), with 87% of dependent youth classified as fast metabolizers. phenotype was associated with NMR ( < 0.001) but not with dependence or use. CONCLUSION: Nicotine dependence in youth using e-cigarettes was linked to nicotine metabolism. The predominance of fast metabolizers among dependent youth suggests varenicline may be more appropriate than NRT as first-line treatment. Future work should evaluate metabolism-informed cessation treatment for youth.

Throughout the history of therapeutic science enzymes play a crucial role in traditional and modern therapeutic practices, with microbial enzymes being a sustainable and efficient biocatalytic resource for pharmaceutical and biomedical applications. This review provides a comprehensive examination of microbial enzymes, covering their structural and biochemical properties, production optimization, purification methods, kinetic behavior, and their applications in pharmaceutical and therapeutic fields. We systematically surveyed the peer-reviewed literature to synthesize current knowledge on microbial enzyme sources, strain development strategies, fermentation optimization, downstream purification, kinetic characterization, and pharmaceutical applications. Microbial enzymes dominate the global enzyme market due to their selectivity, efficiency, scalability, and cost-effectiveness. Advances in molecular biology and genetic engineering have led to the development of enzymes with enhanced stability and activity. Immobilization and nanotechnology have further improved enzyme stability, reduced degradation, and lowered production costs, expanding their pharmaceutical and therapeutic potential. Microbial enzymes are versatile biocatalysts with significant pharmaceutical value, and ongoing research into novel enzyme candidates and advanced biotechnological approaches is crucial for enhancing enzyme-based therapies. We contend that microbial enzymes will remain central to future drug development, offering sustainable, biocompatible, and highly specific solutions to unmet medical needs across oncology, metabolic disorders, inflammation, and infectious disease.

OBJECTIVE: To evaluate whether the addition of botulinum toxin type A (BTX) to celiac plexus block (CPB) is associated with improved analgesic outcomes in patients with pancreatic cancer pain. DESIGN: Retrospective observational study. SETTING: Single-center tertiary hospital. SUBJECTS: A total of 60 patients with pancreatic cancer pain who underwent fluoroscopy-guided CPB between January 2022 and November 2025. METHODS: Patients were divided into CPB only (n = 34) and CPB with BTX (n = 26) groups. Pain intensity (numerical rating scale, NRS), opioid consumption (morphine milligram equivalents, MME), and need for rescue interventions were assessed at 4, 8, and 12 weeks. The primary outcome was the proportion of positive responders at 4 weeks, defined as ≥ 2-point reduction in NRS from baseline, no increase in opioid use, and no additional interventions. RESULTS: The proportion of positive responders at 4 weeks was significantly higher in the CPB + BTX group compared to the CPB only group (65.4% vs. 8.8%, p < 0.001), with sustained differences at 8 and 12 weeks. The CPB + BTX group showed significantly lower pain scores at all follow-up time points and required fewer rescue interventions, including no cases of neurolysis. Kaplan-Meier analysis demonstrated a longer duration of analgesic response in the CPB + BTX group (p < 0.001). In multivariable analysis, BTX use was independently associated with treatment success (OR = 20.75, p < 0.001), while distant metastasis was a negative predictor. No serious adverse events were observed. CONCLUSIONS: CPB with BTX was associated with improved analgesic outcomes for pancreatic cancer pain compared to CPB only. The addition of BTX resulted in higher responder rates, sustained pain reduction, and reduced need for rescue interventions. BTX may represent a non-destructive adjunct to CPB and warrants further prospective validation.

BACKGROUND: Synthetic control arms (SCAs) derived from historical trial data can complement randomized controlled trials (RCTs), particularly in oncology where feasibility, ethical, and cost constraints may limit conventional trial designs. However, their validity for overall survival (OS) remains uncertain. We evaluated the feasibility and limitations of constructing SCAs from the ARCAD metastatic colorectal cancer (mCRC) database across multiple treatment lines. METHODS: Seven landmark RCTs representing first-, second-, and third-line settings were selected. External control arms were constructed from ARCAD individual patient-level data using propensity score matching based on key clinical and biological variables from a validated ARCAD prognostic score, with adjustment for geographic region and time era when needed. A prespecified two-step benchmarking framework assessed: (1) control-arm OS reproducibility and (2) virtual trial comparisons between matched synthetic controls and original RCT experimental arms. Agreement was evaluated using hazard ratios (HRs) and Z-tests. RESULTS: A total of 28,022 patients met the inclusion criteria. ARCAD-derived SCAs were successfully constructed for all selected RCTs and closely reproduced control-arm OS. After matching, baseline characteristics were well balanced, with minimal differences between included and excluded patients. Virtual trials showed concordant treatment-effect estimates with the original RCTs, with a median absolute HR deviation of 0.05 and no significant differences by Z-tests (P>.05). Survival outcomes were consistently reproduced across treatment lines. CONCLUSION: ARCAD-derived SCAs reliably reproduced control-arm OS and benchmark treatment-effect estimates from landmark RCTs in mCRC. Despite limitations related to residual confounding and missing data, this framework supports benchmarking, trial design, and exploratory analyses when conventional control arms are impractical.

AIM: To identify and describe the medication information needs and preferences of caregivers of children with cancer, and the factors that support or impede those needs being met. DESIGN: Qualitative descriptive study guided by reflexive thematic analysis. METHODS: Between November 2024 and July 2025, semi-structured interviews were conducted with 13 caregivers purposively recruited from a tertiary paediatric oncology centre in Australia. Data collection and analysis proceeded concurrently using reflexive thematic analysis. RESULTS: Caregivers described receiving supportive medication information, yet their information needs persisted as responsibility for medication management shifted to families. Needs reflected the practical, emotional, and cognitive demands of translating clinical instructions into safe home-based care. Caregivers relied on visual tools, written schedules, and trusted clinicians to support medication management. High satisfaction with medication information coexisted with vigilance and uncertainty, highlighting a gap between information provision and the realities of home-based medication management. CONCLUSION: Medication information needs in paediatric oncology are dynamic and linked to the transfer of responsibility to families. Phased, system-integrated approaches that support caregivers during care transitions and treatment are required. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Reconceptualising medication information as an iterative process rather than a discrete event is recommended. Transition support, decision aids, and standardised visual medication tools may reduce cognitive burden and enhance medication safety. IMPACT: This study addresses the gap between providing medication information and how caregivers manage complex home-based regimens. Unmet needs stem from the demands of medication administration during care transitions and when managing 'as required' medicines. Findings offer practical insights for paediatric oncology nurses, pharmacists, and policymakers designing transition processes and medication safety strategies in family-managed cancer care. REPORTING METHOD: Consolidated Criteria for Reporting Qualitative Research 32-item checklist. PUBLIC CONTRIBUTION: Caregivers reviewed the interview guide prior to interviews and were invited to provide feedback; no changes were required.

BACKGROUND: Older adults undergoing lumbar spine fusion are vulnerable to impaired postoperative recovery and persistent postsurgical pain. Dexmedetomidine-ketamine-based multimodal general anesthesia may reduce volatile anesthetic and opioid exposure, but its efficacy and tolerability in older adults undergoing high-pain spine surgery remain uncertain. This randomized controlled trial evaluated whether electroencephalographic spectrogram-guided multimodal general anesthesia improves early recovery compared with conventional balanced anesthesia. METHODS: Patients aged ≥60 years undergoing elective lumbar spine fusion were randomized 1:1 in a parallel-group, superiority design to receive either dexmedetomidine-ketamine-based multimodal general anesthesia guided by electroencephalographic density spectral array monitoring or conventional bispectral index-guided balanced anesthesia. All patients received standardized perioperative care. The primary efficacy outcome was the 24-hour change in Quality of Recovery-15 (QoR-15) score from baseline, analyzed as the between-group difference in mean change score. Secondary outcomes included opioid requirements, 3-month pain outcomes, and safety and tolerability outcomes. All secondary outcomes, including the 3-month pain outcomes, were exploratory. RESULTS: Among 100 randomized patients, 50 were assigned to each group. The multimodal general anesthesia group had a smaller 24-hour decline in QoR-15 score than the control group (-22.5 vs -33.5 points; mean difference, 11.0; 95% confidence interval, 0.8-21.2; p=0.036). Multimodal general anesthesia reduced sevoflurane consumption [28 (22-42) vs 43 (36-53) mL; p<0.001], intraoperative fentanyl dose [150 (100-200) vs 200 (125-250) μg; p=0.003], and post-anesthetic care unit morphine requirement [0 (0-2) vs 2 (0-3) mg; p<0.001], at the expense of increased intraoperative norepinephrine and atropine requirements. No significant between-group differences were observed in postoperative safety outcomes, although the trial was not powered to exclude clinically relevant differences. Exploratory 3-month analyses showed lower average pain intensity in the multimodal general anesthesia group [1 (0-2) vs 2 (0-4); p=0.033], whereas the proportion of pain-free patients did not differ significantly [41.7% vs 28.0%; p=0.203]. CONCLUSION: Dexmedetomidine-ketamine-based multimodal general anesthesia implemented with spectrogram-guided titration improved early patient-centered recovery and reduced immediate perioperative opioid requirements, at the expense of increased intraoperative vasopressor and atropine use. Exploratory analyses suggested a possible reduction in 3-month average pain intensity, which requires confirmation in trials adequately powered for persistent postsurgical pain. TRIAL REGISTRATION: NCT05247177.

SHMT2 (serine hydroxymethyltransferase 2) is a pivotal enzyme in cellular metabolism and is closely associated with the initiation and progression of malignant tumors, garnering significant attention in cancer research and therapy. Aberrant expression of SHMT2 has been observed in various cancers, correlating with tumor aggressiveness and patient prognosis. Functionally, SHMT2 participates in one-carbon metabolism, supplying methyl donors and biosynthetic precursors to support tumor cell proliferation. Additionally, it modulates redox homeostasis, promoting cancer cell survival and progression. SHMT2 also interacts with key signaling pathways, including JAK2/STAT3 and Akt/mTOR, thereby influencing tumor cell growth, invasion, and metastasis. Further elucidation of the molecular mechanisms by which SHMT2 contributes to tumorigenesis may provide critical insights for precision diagnosis, targeted therapy, and prognostic evaluationin oncology.

BACKGROUND: Predicting long-term benefit from CDK4/6 inhibitors in HR+/HER2- advanced breast cancer remains challenging in routine clinical practice. We evaluated whether a simple composite index integrating early neutropenia and mean corpuscular volume change, termed the MCV-Neutropenia Risk Score (MNRS), could improve early prognostic stratification. METHODS: In this multicenter retrospective study, 432 patients were screened, and 273 patients who were alive and evaluable at the predefined 3-month landmark were included in the final analysis. Grade 2-3 neutropenia during the first three months and ΔMCV ≥10 fL at the landmark assessment were assigned one point each to construct the MNRS (range, 0-2). Landmark overall survival (OS), measured from the 3-month landmark, was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression. Internal bootstrap validation with 1,000 resamples was performed. RESULTS: After a median landmark follow-up of 44.9 months, 77 deaths were recorded. Grade 2-3 neutropenia occurred in 205 patients (75.1%), ΔMCV ≥10 fL in 93 patients (34.1%), and 66 patients (24.2%) had an MNRS of 2. Higher MNRS categories were associated with progressively more favorable landmark OS (log-rank p = 0.009). In the final center-stratified multivariable model, each one-point increase in MNRS was independently associated with a lower risk of death (HR 0.555, 95% CI 0.381-0.808; p = 0.002). Internal bootstrap validation supported the stability of MNRS in the multivariable model. CONCLUSION: Among patients who were alive and evaluable at the 3-month landmark, higher MNRS was independently associated with more favorable subsequent landmark OS. MNRS may represent an exploratory and complementary approach to early risk stratification using routinely available hematologic parameters. Because both neutropenia and MCV changes may be influenced by treatment exposure and other clinical factors, prospective external validation is required before clinical application.

BACKGROUND: The optimal locoregional treatment to combine with lenvatinib and PD-1 inhibitors for hepatocellular carcinoma with portal vein tumor thrombus (PVTT-HCC) remains uncertain. We compared HAIC- and TACE-based triple therapy. METHODS: This retrospective single-center study included 359 consecutive patients with PVTT-HCC treated with HAIC or TACE plus lenvatinib and a PD-1 inhibitor. Propensity score matching (PSM) was performed at a 1:1 ratio. Tumor response was assessed using mRECIST. Overall survival (OS), progression-free survival (PFS), conversion-to-surgery, and adverse events were compared. Time-dependent Cox models accounted for cumulative locoregional treatment sessions. RESULTS: Among 359 patients, 161 received TACE-based therapy and 198 received HAIC-based therapy. After PSM, 139 matched pairs were analyzed. HAIC was associated with higher objective response rate (66.91% vs 42.45%) and disease control rate (82.73% vs 62.59%) than TACE (both <0.001). Median OS was 23.7 versus 17.1 months (HR 0.67, 95% CI 0.48-0.93; =0.018), and median PFS was 7.7 versus 5.4 months (HR 0.70, 95% CI 0.54-0.91; =0.008), favoring HAIC. After time-dependent adjustment, HAIC remained associated with improved OS (HR 0.61; =0.003) and PFS (HR 0.73; =0.011). Conversion-to-surgery was more frequent with HAIC (27.3% vs 17.4%; =0.027). Overall adverse-event rates were similar (89.90% vs 88.82%; =0.741), although hypertension was more frequent with HAIC (52.02% vs 38.51%; =0.011). CONCLUSION: In patients with PVTT-HCC receiving lenvatinib and PD-1 inhibitors, HAIC-based triple therapy was associated with improved tumor response and longer OS and PFS than TACE-based therapy, with generally comparable safety. Prospective multicenter studies are warranted.

The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling, primarily comprising FGFs, FGFRs, and the co-receptor Klotho, regulates key physiological processes, including embryogenesis, tissue homeostasis, metabolism, and neurodevelopment. Dysregulation of FGF/FGFR signaling, whether resulting from pathological hyperactivation or loss-of-function, is implicated in multiple diseases such as skeletal dysplasia, metabolic disorders, cancers, and neurological disorders. Consequently, correction of causative FGF/FGFR signaling represents a promising clinical strategy. Despite the deepening understanding of the FGF/FGFR signaling, its clinical translation still faces challenges, including side effects and acquired resistance to pathway blockade, as well as safety concerns regarding FGF analogs. Herein, we provide an overview of FGF/FGFR signaling and summarize its cellular and physiological functions. We further delve into the relationship between aberrant (including hyperactivated or inactivated) FGF/FGFR signaling and diverse diseases. Additionally, we also discuss the strategies targeting the causative FGF/FGFR signaling, as well as offer new perspectives for optimizing these targeted therapies. Collectively, this review will contribute to the development of more precise strategies for the targeted regulation of dysregulated FGF/FGFR signaling.

BACKGROUND: Postoperative pneumonia (PP) after esophagectomy arises from interacting pulmonary, aspiration, airway-protection, perioperative-care, and host-response pathways. Whether the preoperative fibrinogen-to-prealbumin ratio (FPR), a marker integrating inflammatory-coagulative activity and nutritional-inflammatory reserve, is associated with in-hospital PP after minimally invasive McKeown esophagectomy remains uncertain. METHODS: Using routinely collected electronic medical-record data, consecutive patients with pathologically confirmed esophageal squamous cell carcinoma (ESCC) who underwent elective minimally invasive McKeown esophagectomy from January 2023 to December 2025 were retrospectively analyzed. FPR was expressed on the ×1000 scale and analyzed continuously per 1-unit and per 1-standard-deviation (SD) increase. The primary endpoint was in-hospital PP. Sequential multivariable logistic regression, restricted cubic splines, infection-phenotype and microbiological description, multicollinearity diagnostics, and clinically defined sensitivity analyses were performed. A complete-case 30-day PP analysis was included as a sensitivity analysis. Selectively performed airway and swallowing assessments were analyzed descriptively only. RESULTS: Among 437 patients, 139 (31.8%) developed in-hospital PP. In the primary fully adjusted clinical model, each 1-unit increase in FPR ×1000 was associated with higher odds of PP (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.23-1.41; P<0.001); the OR per 1-SD increase was 4.40 (95% CI 3.09-6.29; P<0.001). Restricted cubic spline analysis supported an overall graded association (P for overall <0.001; P for non-linearity=0.162). Results remained consistent in the complete-case 30-day analysis and other sensitivity analyses. Median PP onset was postoperative day 5; 25.2% of cases were classified as aspiration-likely, and 44.7% of cultured cases were culture positive. CONCLUSION: Higher preoperative FPR was associated with in-hospital PP after minimally invasive McKeown esophagectomy for ESCC. These single-center retrospective findings are hypothesis-generating and do not establish causality or immediate clinical utility. Prospective multicenter and external validation is required before FPR is used for perioperative risk stratification.