The CHA₂DS₂-VASc score includes classical risk factors (e.g., Congestive heart failure/Left ventricle dysfunction, Hypertension, Age, Diabetes mellitus, Stroke/Transient ischemic attack/Thromboembolism, Vascular disease and Sex) for coronary artery disease. We investigated the association between initial thrombolysis in myocardial infarction (TIMI) flow of the culprit artery and CHA₂DS₂-VASc score and in-hospital clinical outcomes in patients presenting with acute myocardial infarction (AMI). Initial and postprocedural TIMI flow grades were recorded in patients hospitalized with first diagnosis of AMI. The initial TIMI flow grades and CHA₂DS₂VASC scores were compared with the post-procedural TIMI flow grades. Patients (n = 750) were included retrospectively; 56.7% was in the low flow (TIMI 0-1) and 43.3% was in the high flow (TIMI 2-3) group. The CHA₂DS₂-VASc score was higher (P < .001) in the low flow group. The best CHA₂DS₂-VASc score cut-off value was 3 to predict initial TIMI flow. Median CHA₂DS₂-VASc score was 4 in-hospital mortality group (P < .001) and this score was an independent predictor of in-hospital mortality. The CHA₂DS₂-VASc score was an independent predictor of low initial TIMI flow and in-hospital mortality. Patients with high preprocedural CHA₂DS₂-VASc tended to have low coronary flow grades and higher mortality rates.

COMPEL (NCT04765059) was a global, randomized, double-blind study that evaluated osimertinib plus chemotherapy versus placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) following non-central nervous system (CNS) progression on first-line osimertinib.

Patients were randomly assigned to receive osimertinib 80 mg, or placebo, once daily (o.d.) in combination with chemotherapy [cisplatin 75 mg/m² or carboplatin area under the curve 5 plus pemetrexed 500 mg/m² every 3 weeks (q3w) for four cycles], followed by osimertinib 80 mg, or placebo, o.d. in combination with maintenance pemetrexed (500 mg/m² q3w) until progression. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included CNS PFS according to CNS metastases status at baseline and overall survival (OS).

Ninety-eight patients were randomly assigned (49 per arm). Median PFS in all patients was 8.4 months [95% confidence interval (CI) 5.7-11.8 months] with osimertinib plus chemotherapy versus 4.4 months (95% CI 3.5-5.6 months) with placebo plus chemotherapy [hazard ratio (HR) 0.43, 95% CI 0.27-0.70]. CNS PFS was longer with osimertinib plus chemotherapy versus placebo plus chemotherapy (HR 0.56, 95% CI 0.27-1.13) in patients without baseline CNS metastases (n = 75). Median OS in all patients was 15.9 months (95% CI 12.4-20.8 months) with osimertinib plus chemotherapy versus 9.8 months (95% CI 8.4-17.2 months) with placebo plus chemotherapy (HR 0.71, 95% CI 0.42-1.23). Grade ≥3 adverse events occurred more frequently with osimertinib plus chemotherapy (63%) than placebo plus chemotherapy (46%).

In patients with non-CNS progression on first-line osimertinib, osimertinib plus chemotherapy was associated with improved PFS and longer OS compared with placebo plus chemotherapy. These findings support osimertinib as a backbone treatment for EGFR-mutated advanced NSCLC through lines of therapy.

IntroductionIn Japan, while public health insurance ensures evidence-based-care, high-cost private medical practices offer advanced interventions-collectively referred to as "X" in this study-which have limited scientific evidence but have raised ethical and clinical concerns, particularly in oncology. This study explores oncologists' perceptions and responses to X in practice to inform appropriate countermeasures.MethodsMembers of the Japanese Society of Medical Oncology (n = 6273) completed a questionnaire survey between April 24 and June 10, 2024. The survey explored the oncologists' evaluations of X, their responses to patient inquiries about such interventions, and their personal preferences if they were personally diagnosed with cancer.ResultsOf 828 valid responses (response rate: 13.2%), 63.4% of oncologists reported receiving patient inquiries about X in the past year. Overall, 76.4% gave a negative evaluation of X, while over 90% provided negative ratings on 7 out of the 9 specific items. Despite this, many oncologists reported a neutral stance when discussing X with the patients. Notably, even without standard of care options, most indicated that they would not choose X for themselves. The findings reveal a considerable gap between oncologists' evaluation of X and what they convey when communicating with the patients. Qualitative responses expressed concerns about insufficient follow-up care and potential exploitation of vulnerable patients.ConclusionThis study highlights the need for more transparent, evidence-based communication between oncologists and patients regarding X. Enhancing such dialogue is essential for supporting informed decision-making and maintaining the integrity of cancer care in the face of unproven private medical interventions. Furthermore, considering X's profound negative impact on patients, society, and the field of medicine, legitimate medical professionals must conduct clear and accurate evaluations of X to facilitate the understanding of the patients and general public.

Myeloproliferative neoplasms (MPNs) are symptom-driven hematologic malignancies characterized by persistent and heterogeneous symptom burden that significantly impairs health-related quality of life (HRQoL). This burden is intrinsically linked to MPN pathophysiology, including splenomegaly, inflammatory cytokine release, and microvascular dysfunction, underscoring the need for MPN-specific patient-reported outcome measures (PROMs) to quantitatively assess symptoms and sensitively capture treatment responses. Initial instruments such as the Myelofibrosis Symptom Assessment Form (MF-SAF) and MPN Symptom Assessment Form (MPN-SAF) evaluated both symptom burden and HRQoL. To meet regulatory standards for JAK inhibitor trials, subsequent versions, such as MF-SAF v2.0 and the MPN-SAF Total Symptom Score (TSS), shifted focus toward symptom-specific endpoints, with a ≥ 50% reduction in TSS (TSS50) considered a clinically meaningful response. To improve consistency and methodological rigor, the MF-SAF was further refined into version 4.0, which has served as a primary endpoint in pivotal trials such as MOMENTUM, often in combination with validated generic HRQoL instruments. These PROMs have played a pivotal role in securing regulatory approvals for agents such as ruxolitinib and momelotinib. While TSS50 remains the standard endpoint in clinical trials, its dichotomous nature presents limitations; emerging evidence suggests that evaluating TSS as a continuous variable may offer greater sensitivity in capturing treatment effects. In clinical practice, the MPN-SAF TSS is increasingly used to guide symptom monitoring and personalized decision-making. This review outlines the evolution, validation, and clinical impact of MPNs-symptom-specific PROMs, underscoring their growing role in delivering precision, patient-centered care.

Lateral lymph node dissection (LLND) remains controversial owing to differences in oncological principles between East and West, complex pelvic anatomy and the risk of complications. The aim of this systematic review is to determine the number of cases required to achieve surgical competence in LLND and to evaluate postoperative outcomes across different phases of the learning curve.

A systematic literature search was conducted in PubMed and Google Scholar for studies analyzing the LLND learning curve in rectal cancer resection. The three-phase pattern, consisting of learning, competence, and proficiency, was followed for data analysis and presentation. A separate learning curve analysis for open, laparoscopic and robotic LLND was performed. Blood loss, operative time, lymph node yield, urinary complications and postoperative morbidity were assessed across the phases of the learning curve for robotic LLND.

Of the 616 articles screened, eight studies met the inclusion criteria. Seven studies reported the learning curve analysis for robotic LLND, and one study for laparoscopic and open approach. Five studies had operative time as a learning outcome, two studies the lymph node yield and one study both lymph node yield and urinary retention. All studies used the cumulative sum (CUSUM) method for learning curve analysis. Regardless of learning outcome, surgical competence for robotic LLND was achieved after 12-53 cases, for laparoscopic LLND after 19 cases, and for the open approach no inflection point was identified. In robotic LLND, blood loss, urinary complications, and morbidity decreased during the proficiency phase.

The LLND learning curve is not yet standardized owing to variability in study design, type of LLND, and learning outcomes. Further well-designed and methodologically consistent studies are required to establish learning benchmarks and improve patient outcomes.

CRD420251050015.

Colon adenocarcinoma (COAD) is highly malignant tumor in the gastrointestinal tract, and reliable biomarkers for predicting its prognosis are remain lacking. MIER Family Member 2 (MIER2) has been implicated in tumor biology, yet its role in COAD remains unclear. MIER2 expression in COAD was analyzed using TCGA and UALCAN databases. Survival analysis, Cox regression, and nomogram construction were performed to evaluate its prognostic value. Functional enrichment analysis was conducted via LinkedOmics. Immune infiltration was assessed using ESTIMATE and CIBERSORT algorithms. Additionally, the effect of MIER2knockdown on the proliferation, and migration of SW480 cell was evaluated. The expression of MIER2 was significantly higher in COAD tissues and associated with a poorer OS, DSS and PFI. Multivariate analysis confirmed MIER2 as an independent prognostic factor. Co-expressed gene analysis revealed enrichment in immune-related pathways, including type I interferon signaling and macrophage activation. In addition, MIER2 expression was associated with altered immune infiltration. MIER2 knockdown suppressed SW480 cell proliferation and migration, and RNA-seq further indicated that this might be related to the intrinsic apoptotic signaling pathway. High expression of MIER2 is associated with poor prognosis and immune cell infiltration, and it serve as a novel prognostic biomarker and potential therapeutic target for COAD.

Although immunotherapy has demonstrated clinical efficacy in advanced gastric cancer (AGC), its therapeutic benefits are limited to a subset of patients. This study aimed to evaluate circulating cytokines as potential prognostic biomarkers to enhance the precision of clinical decision-making in PD-1 inhibitor-based immunotherapy for AGC. A total of 269 patients with advanced gastric cancer were enrolled according to predefined inclusion criteria. Among them, 117 patients received anti-PD-1 immunotherapy combined with chemotherapy (immunochemotherapy), while 152 received chemotherapy alone. Plasma levels of 12 cytokines were quantified using flow cytometry, and appropriate statistical analyses were performed. Compared with healthy controls, plasma concentrations of IL-6, IL-8, and IL-10 were significantly elevated in AGC patients. Furthermore, levels of these cytokines were markedly higher in the immunochemotherapy no response group compared to both the chemotherapy-alone group and response group. Multivariate analysis confirmed that IL-6, IL-8, and IL-10 were independent risk factors for poor treatment outcomes in patients receiving immunochemotherapy. Notably, the combined measurement of these three cytokines provided superior diagnostic accuracy compared to individual markers. The present study preliminarily demonstrates that IL-6, IL-8, and IL-10 cytokines may serve as potential predictive biomarkers for treatment outcomes in patients with AGC receiving anti-PD-1 immunochemotherapy. These easily accessible blood biomarkers are predictive and rapid and may play a key role in identifying individuals who may benefit from PD-1 blockade immunotherapy.

The HCC biomarkers, Lens culinaris agglutinin fraction of AFP (AFP-L3) and des-gamma-carboxyprothrombin (DCP) with AFP, have been approved for surveillance in HCC but have not yet impacted disease management. In this prospective study, AFP, AFP-L3, and DCP were assessed as a non-invasive strategy to monitor residual disease and post-LDT changes in association with risk of disease progression. The biomarkers were measured at HCC diagnosis and following first cycle LDT. Response to LDT was evaluated using mRECIST. Time to event endpoints included time to advanced-stage disease progression, duration of overall complete response (oDoCR), and overall survival. The study included 182 patients with diverse biomarker profiling both at diagnosis and following first cycle LDT. Despite treatment, persistent biomarker expression was found in 36% (66/182) of patients with most (50/66) having elevations in AFP-L3 and/or DCP (AFP-L3⁺/DCP⁺). Overall CR rates were highest in patients treated to triple negative/AFP⁺ only (61%) compared to AFP⁺AFP-L3⁺/DCP⁺ (30%) or AFP_NEGAFP-L3⁺/DCP⁺ (22%) phenotypes. In patients expressing AFP-L3⁺/DCP⁺ that achieved an overall CR, the oDoCR was lower compared to patients treated to triple negative/AFP⁺. Higher 1-year stage progression rates were also observed in patients with AFP-L3⁺/DCP⁺ phenotypes. Overall survival was lowest in patients expressing AFP⁺AFP-L3⁺/DCP⁺ (2-year rate: 36%). In patients with an incomplete response, triple negative/AFP⁺ phenotypes had longer TTP compared to AFP-L3⁺/DCP⁺ phenotypes (median TTP: 63 months vs 10 months). Sustained AFP-L3⁺/DCP⁺ expression following LDT may be associated with aggressive residual tumor contributing to an incomplete response, increased risk of disease stage progression, and inferior survival outcomes.

With the increasing utility of the single-port (SP) robotic platform, there remains limited evidence surrounding the perioperative morbidity associated with the novel techniques. This study sought to evaluate the incidence of venous thromboembolic events (VTE) associated with the SP procedures for upper and lower tract urological malignancies, based on the multi-institutional experience of the Single-Port Advanced Research Consortium (SPARC), involving a total of 2286 patients. The group comprised 1886 (82.5%) and 400 (17.5%) cases of SP robotic radical prostatectomy (RARP) and SP robotic partial nephrectomy (RAPN) that were completed between 2018 and 2024. In addition to the perioperative variables, all patients were stratified into low, moderate, and high risk for VTE according to the Caprini scoring system. Notably, no cases of VTE were identified following SP-RAPN, while eight cases of DVT (0.42%) and two cases of PE (0.11%) were diagnosed following SP-RARP. Appreciating the different risk factors of VTE, a higher Caprini score was identified to be associated with VTE, with every one-point increase in the score contributing to 1.6 times higher odds of VTE following SP-RARP. In summary, this study demonstrated the relatively low incidence of VTE associated with SP robotic procedures for upper and lower tract urological malignancies (0.44%). The utility of validated tools such as the Caprini scoring system can provide additional benefits to identify at-risk patients and provide foundations for further research to better select candidates for mechanical and pharmacological thromboprophylaxis and, thus, ensure satisfactory perioperative outcomes.

Small cell lung cancer (SCLC) is one of the most aggressive malignancies, with early detection being crucial for improving patient outcomes. Serum biomarkers, neuron-specific enolase (NSE), and pro-gastrin releasing peptide (ProGRP), play significant roles in the early screening and pathological classification of SCLC. In the study, the affinity peptides of NSE and ProGRP were screened by phage display technology, which were then assessed for binding affinity using enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry (BLI). Circularly permuted fluorescent protein (cpFP) probes were constructed by genetically encoding the selected peptides as binding domains. The E1 probe for NSE and the P10 probe for ProGRP demonstrated high sensitivity and specificity in detecting their respective targets. The E1 probe with a concentration of 4 μg/mL reacted well with NSE (1-16,000 ng/mL), and the reaction exhibited a good linear relationship when the NSE concentration was between 1 and 100 ng/mL. The 4 μg/mL P10 probe reacted well with ProGRP (0.01-2000 ng/mL) and showed good linear relationship between 0.01 and 50 ng/mL. Clinical validation revealed that adjusting the upper limit of normal concentrations significantly improved the probes' diagnostic sensitivity and specificity for SCLC. These probes offer a high-sensitivity, specific, rapid, and cost-effective approach to SCLC detection, holding promise for early diagnosis and improved patient management . KEY POINTS: In this study, peptides targeting NSE and ProGRP were selected by phage display technology, and the peptides obtained have good affinity with the corresponding proteins. Based on R-GECO1, cpFP probes were constructed using peptides as binding domains, and E1 probe for NSE and P10 probe for ProGRP were obtained. E1 probe and P10 probe have good sensitivity and specificity for the diagnosis of SCLC.