Questioning adjuvant therapy and surveillance in octogenarians after right hemicolectomy.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available and inexpensive agents with proposed antitumor activity, particularly in tumors harboring PIK3CA mutations. This meta-analysis of randomized controlled trials (RCTs) evaluated whether adjuvant NSAID therapy improves outcomes in patients with resected PIK3CA-mutated colorectal cancer (CRC). PubMed, Embase, and the Cochrane Library were systematically searched for RCTs assessing NSAID use following curative-intent resection of CRC in patients with confirmed PIK3CA mutations. Pooled hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were calculated for disease-free survival (DFS) and overall survival (OS) using both fixed and random-effects models. Sensitivity analyses excluded participants with low-dose aspirin exposure concomitant with cyclooxygenase-2 (COX-2) inhibitors. Among 477 records screened, four RCTs met eligibility criteria, comprising 426 patients assigned to NSAIDs (aspirin or COX-2 inhibitors) and 363 receiving placebo. Adjuvant NSAID therapy improves DFS (HR 0.65; 95 % CI, 0.46-0.90). In sensitivity analyses excluding concomitant aspirin exposure, a similar magnitude of effect was observed (HR 0.57; 95 % CI, 0.39-0.83). The pooled OS analysis was not statistically significant (HR 0.78; 95 % CI, 0.39-1.57). Exclusion of low-dose aspirin users was associated with lower mortality risk (HR 0.54; 95 % CI, 0.30-0.99), although these findings should be interpreted cautiously. Adjuvant NSAID therapy is associated with improved DFS in patients with PIK3CA-mutated CRC. OS benefit remains uncertain, and findings from sensitivity analyses are exploratory. These findings support consideration of NSAIDs as a biomarker-informed adjuvant strategy in selected patients while underscoring the need for confirmatory evidence from ongoing randomized trials.

Optimal adjuvant intravesical therapy for intermediate risk non-muscle invasive bladder cancer; oncological and patient-reported outcomes of randomized controlled trial.

Neoadjuvant stereotactic body vs conventionally fractionated radiation therapy for borderline resectable and locally advanced pancreatic cancer: a propensity score-matched analysis.

Case series report on long-term result of endovascular approach to thrombosed limb or limb graft occlusion of aortoiliac endoprosthetic stent graft using the first-order percutaneous mechanical arterial advanced thrombectomy technology protocol.

Neuroprotective effects of Tongxinluo capsule in acute ischemic stroke: A systematic review and meta-analysis.

Mapping the global landscape of biologics in allergic diseases: A bibliometric analysis.

Targeting PFKFB3-dependent endothelial-mesenchymal transition by luteolin attenuates doxorubicin-induced cardiotoxicity.

Divergent Differentiation and Histologic Subtypes in Upper Tract Urothelial Carcinoma Demonstrate Distinct Patterns of Extraurothelial Recurrence.

Distinct clinicopathologic features and efficacy of adjuvant therapy in intraductal papillary mucinous carcinoma compared with conventional pancreatic ductal adenocarcinoma.

Objective: To compare and analyze the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs) as adjuvant therapy after surgery for hepatocellular carcinoma (HCC) with microvascular invasion (MVI). Methods: Patients with HCC accompanied with MVI who underwent R0 liver resection at the First Medical Center of the PLA General Hospital between January 2016 and December 2024 were retrospectively enrolled. The clinicopathological data, surgical details, and follow-up data were recorded. Adverse events after medication were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Recurrence-free survival (RFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method and compared with the Log-rank test. The Cox proportional hazards regression model was used to analyze factors influencing recurrence. Results: The study included 39 patients in the adjuvant therapy group and 41 patients in the follow-up observation group. There were no significant differences in baseline characteristics between the two groups (all P>0.05). The follow-up time [M(Q1, Q3)] was 21.8 (10.9, 50.7) months. The RFS rates at 6, 12, 24, and 36 months in the adjuvant therapy group were 92.3%, 76.0%, 71.2%, and 51.8%, respectively, all higher than those in the follow-up observation group (75.1%, 56.3%, 44.3%, and 16.9%). The median RFS in the adjuvant therapy group was 46.7 months (95%CI:15.19-78.22), significantly better than the 19.33 months (95%CI: 3.22-35.44) in the follow-up observation group (P=0.004). The median OS was not reached in either group(P=0.480). Multivariate Cox analysis showed that postoperative adjuvant therapy (HR=0.46, 95%CI: 0.24-0.89, P=0.020) and liver cirrhosis (HR=2.22, 95%CI: 1.00-4.92, P=0.050) were influencing factors for RFS. In terms of safety, 43.59% (17/39) of patients in the adjuvant therapy group experienced grade 1-4 adverse events, and 15.38% (6/39) experienced grade 3 or higher adverse events, primarily manifested as abnormal liver and kidney function, rash, etc. No treatment-related deaths occurred, and the safety profile was manageable. Conclusion: For patients with HCC accompanied by MVI, postoperative adjuvant therapy with immunotherapy combined with targeted therapy significantly prolongs recurrence-free survival, reduces the risk of recurrence, and demonstrates a manageable safety profile.

Hypoxic ischemic encephalopathy (HIE) is a severe brain injury that can lead to death and long-term disability. HIE can be treated with therapeutic hypothermia, and various adjuvant treatments (such as melatonin) are also utilized. Adjuvant therapies are not recommended outside clinical trials, and therapeutic hypothermia is not universally available. This study aimed to investigate the effects of Edaravone on improving levels of consciousness, hemodynamic stability, and short-term clinical outcomes of adult patients with severe HIE. To the best of our knowledge, this study is the first randomized clinical trial investigating the effects of Edaravone in adult patients with severe HIE. A double-blind clinical trial enrolled 72 severe HIE patients (aged > 18) within 24 h of onset who were diagnosed clinically and radiologically. Patients were randomized to Edaravone group (n = 20) and non-Edaravone group (n = 52). Measured parameters included level of consciousness, vital signs, Barthel index, and patient outcome (death or discharge). Statistical analysis was performed using SPSS version 27, with a significance level of P < 0.05. In short-term assessment of the patient's level of consciousness, the Edaravone group showed significant improvement in the Glasgow Coma Scale (GCS) post-intervention (p = 0.001). While the Edaravone group and non-Edaravone group showed no significant difference in outcome (p = 0.863) and Barthel score for discharged patients (P = 0.557). Vital signs showed significant differences between groups in temperature (P = 0.002). In the comparison of comorbidities between the Edaravone and non-Edaravone groups, only coronary artery bypass grafting was significantly different (P = 0.021). Edaravone improved the short-term level of consciousness in severe HIE adult patients, but there was no significant effect on outcome and level of independence in performing activities of daily living. Further investigation into Edaravone's effectiveness is warranted, particularly in patients with milder forms of HIE, as well as longer follow-up periods.

Surgical resection is a frontline treatment for many solid tumors; however, residual tumor cells in the surgical cavity often lead to recurrence and metastasis. Adjuvant therapies are used to mitigate this risk but are frequently limited by systemic toxicity and variable efficacy. Here, we present an injectable, cold atmospheric plasma (CAP)-loaded decellularized tumor extracellular matrix (DECM) hydrogel (denoted as CAP-DECM gel) as a novel in situ tumor-infiltrating immunoactivation platform for post-surgical cancer immunotherapy. These gels combine two critical functionalities: the attraction of residual tumor cells by DECM-derived chemokines and cytokines, and the local induction of immunogenic cell death (ICD) through CAP-derived reactive species. Studies demonstrate that CAP-DECM gels effectively recruit tumor cells, promote ICD hallmarks, activate various immune cells, including dendritic cells and macrophages, and elicit robust T-cell responses. In murine post-resection melanoma and breast cancer models, CAP-DECM gels significantly suppressed tumor recurrence, reprogrammed the tumor microenvironment toward an immune-supportive phenotype, and triggered systemic anti-tumor immunity. Furthermore, combining CAP-DECM gels with anti-PD-L1 checkpoint blockade therapy enhanced long-term survival and conferred resistance to tumor rechallenge. Our results suggest that this tumor-infiltrating immunoactivation platform transforms the surgical cavity into a self-contained immune activation depot and offers a promising, personalized strategy for preventing tumor relapse.

Cost-Utility and Budget Impact Analysis of Tumor Necrosis Factor-Alpha Inhibitors for the Treatment of Refractory Nonsystemic Juvenile Idiopathic Arthritis in Thailand.

Liver-specific delivery of mRNAs encoding key regulatory genes via lipid nanoparticles (LNPs) is promising to restore liver homeostasis and resume liver functions in inflammatory liver diseases. However, inflammation downregulates the global mRNA expression in general as a self-defensive mechanism, e.g., to block viral protein expression, which also reduces the efficiency of therapeutic mRNA delivered to hepatocytes. In addition, ionizable LNPs are immunogenic, which exacerbates inflammation. In this project, we applied a novel immune-modulating telodendrimer (TD) nanodrug (ND) to inhibit inflammation and improve specific mRNA delivery. We tested TD ND in both mouse and human immune cells, liver cell lines, and primary human hepatocytes (PHH) to inhibit endotoxin-induced inflammation. TD ND was able to inhibit both endogenous and LPS-induced inflammation in liver cells, which improved cell proliferation in culture and also significantly enhanced the efficiency of mRNA/LNP delivery both in vitro in human monocytes and PHH. Finally, we demonstrated that TD ND is superior to steroid drugs in inhibiting endotoxin-induced inflammation and sustaining liver function in mice, thereby rebooting the efficacy of liver-targeted LNP mRNA delivery and expression. These findings highlight the potential of TD ND as an effective adjuvant therapy to enhance mRNA delivery for inflammatory disease treatments.

To develop a data-driven risk-stratification model to identify high-risk patients following radical cystectomy (RC) for bladder cancer and propose a risk-adapted follow-up (FU) schedule. We performed a retrospective analysis of an individual patient data registry comprising 3196 patients with clinical T stage (cT)2-T4 N0M0 bladder cancer who underwent RC at 16 European centres (1990-2024). All treatment decisions, including the use of neoadjuvant chemotherapy, adjuvant therapy, and the FU schedule, were made at the discretion of the treating physician in accordance with the patient's preference. A Classification and Regression Tree (CART) analysis, incorporating pathological T and N stages, lymphovascular invasion (LVI), and other features, was used to stratify patients into Low-Risk and High-Risk groups for recurrence. The primary endpoint was recurrence-free survival (RFS). We used a landmark analysis to evaluate the conditional risk of recurrence at 1, 2, 3, 4, and 5 years after RC. At a median FU of 81.8 months, 891 patients recurred. CART analysis identified a High-Risk group (pathological T stage [pT]3-pT4, node-positive disease, or pT2 with LVI) with significantly worse 5-year RFS than the Low-Risk group (37.8% vs 76.2%; P < 0.001). This stratification was strongly prognostic for recurrence (hazard ratio [HR] 4.29; 95% confidence interval 3.63-5.00), cancer-specific survival (subdistribution HR 5.80), and overall survival (HR 3.04) (all P < 0.001). Landmark analysis confirmed that the elevated risk persisted up to 4 years; however, the conditional risk for event-free patients converged after 5 years (HR 1.37; P = 0.3). This study establishes a simple, pathologically derived model (pT3-4/pN+/pT2 + LVI) that effectively stratifies post-RC patients, enabling a risk-adapted FU strategy. Prospective evaluation of this framework is required to confirm its clinical utility, safety, and cost-effectiveness.

Survival Without Adjuvant Therapy for Low-Risk Endometrial Cancer With Isolated Tumor Cells

Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown. The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population. The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries. Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025.

Background and aim Cisplatin is a successful medicinal drug and an efficient chemotherapeutic agent that has a dose-dependent hepatotoxicity. The present study aimed to examine the hepatoprotective function of cirsimaritin against cisplatin-mediated liver injury and to determine whether cirsimaritin affects the antitumor activity of cisplatin. Experimental approach Adult male Wistar rats were pretreated with cirsimaritin (50 or 100 mg/kg, p.o.) for 7 days before a single i.p. injection of cisplatin (7.5 mg/kg). Biochemical, histological, oxidative, and molecular endpoints were evaluated. The anticancer activity of cisplatin alone or in combination with cirsimaritin was measured in MCF-7 breast cancer cells by MTT assay. Key findings The injection of cisplatin resulted in a marked rise in serum ALT and AST levels (p < 0.001), an increase that was significantly inhibited by cirsimaritin at 50 mg/kg (p < 0.01) and 100 mg/kg (p < 0.001). The increased serum triglycerides and total cholesterol (p < 0.001) were significantly attenuated by 100 mg/kg of cirsimaritin (p < 0.05). Hepatic malondialdehyde (MDA) and NOx (nitrate/nitrite), which were elevated by cisplatin (p < 0.001), were decreased by cirsimaritin in a dose-dependent manner (p < 0.01 and p < 0.001, respectively), whereas GSH, which was downregulated by cisplatin (p < 0.001), was upregulated by cirsimaritin (p < 0.01 for 50 mg/kg; p < 0.001 for 100 mg/kg). Histopathology confirmed cirsimaritin-mediated structural restoration. In Western blot analysis, cirsimaritin downregulated nuclear factor-κB (NF-κB) (p < 0.001) and upregulated phosphorylated Akt (p-Akt) expression (p < 0.01). In MCF-7 cells, cirsimaritin (25 and 50 µM) potentiated cisplatin-induced cytotoxicity did not antagonize cisplatin cytotoxicity. Conclusion Our findings also indicate that cirsimaritin induces dose-dependent hepatoprotection against cisplatin toxicity without decreasing its anticancer activity, thus making it a good candidate as adjuvant therapy in oncology.

The limitations of current immune checkpoint inhibitor therapies highlight a need for improved strategies to expand tumor-reactive T cell repertoires in a way that is safe, selective and efficient. Cancer vaccines hold potential to achieve this goal, but the profound success of vaccines for infectious diseases has not yet translated to the cancer setting. Recently, however, encouraging preliminary results from phase 1 and 2 clinical trials have renewed enthusiasm and spurred the initiation of large-scale cancer vaccine trials. In this Review, we highlight insights from recent clinical trials, translational studies and preclinical models, which reveal critical factors for optimizing cancer vaccines. Key strategies include definition of improved proxies to estimate vaccine efficacy, selection of high-quality antigens-particularly neoantigens-using modular vaccine platforms with innate immunostimulatory capabilities, and a focus on early-stage cancer, as exemplified by (neo)adjuvant therapies. We discuss each of these in detail, outlining a roadmap for future cancer vaccine development.