Enterococcus faecalis is a commensal of the human gastrointestinal microbiota that has emerged as a successful opportunistic pathogen associated with persistent infections, antimicrobial resistance, and biofilm formation. Increasing evidence indicates that iron availability functions as a master environmental signal coordinating E. faecalis pathogenic traits. This review summarizes clinical, molecular, and sequencing-based studies linking iron homeostasis to extracellular DNA (eDNA) dynamics, biofilm architecture, virulence regulation, and immune evasion, and critically evaluates the emerging but still associative evidence connecting E. faecalis to colorectal carcinogenesis. We highlight how iron sensing and uptake systems modulate biofilm stability through eDNA release, metabolic cooperation, and transcriptional control via the ferric uptake regulator (Fur) and other regulatory networks. We further integrate experimental findings that suggest how these mechanisms may promote inflammation-driven tumorigenesis in the colon, although a complete causal pathway has not yet been established. Finally, we discuss translational implications, including iron-targeting and eDNA-disruptive strategies as promising anti-virulence approaches, and identify key knowledge gaps requiring future investigation. This review positions iron metabolism at the center of E. faecalis pathogenicity and underscores its potential as a therapeutic target, while recognizing the need for further mechanistic and clinical validation.

Adjuvant anti-programmed cell death protein 1 (anti-PD-1) treatment improves outcomes in high-risk resected melanoma but causes chronic immune-related adverse events (irAEs) in more than 40% of patients. Risk factors associated with chronic vs acute irAEs remain lacking.

To identify factors and possible candidate inflammatory pathways associated with the development of chronic nonendocrine irAEs.

This retrospective cohort study was conducted from January 1, 2015, to December 31, 2024, at 7 institutions in the US and Australia. Patients had stage III to IV melanoma treated with adjuvant anti-PD-1 therapy and more than 12 months of follow-up after discontinuation of anti-PD-1 treatment.

Potential risk factors (age, sex, time to irAE onset, corticosteroid exposure, time to corticosteroid initiation, peak corticosteroid dose, and anti-PD-1 treatment status) for chronic irAEs.

Incidence, type, and risk factors for chronic (persisting ≥3 months after anti-PD-1 therapy cessation) irAEs and cytokine levels at 12 months after immune checkpoint inhibitor initiation were assessed.

Among 303 patients (median age at anti-PD-1 therapy initiation, 64 years [IQR, 55-72 years]; 184 men [61%]), 220 (73%) developed acute irAEs and 146 (48%) developed chronic irAEs. The most common chronic irAEs were hypothyroidism (45 of 146 [31%]), arthritis (25 of 146 [17%]), and dermatitis (17 of 146 [12%]). Chronic irAEs had later onset (median, 153.0 days [IQR, 67.0-294.0 days] vs 99.0 days [IQR, 32.2-228.8 days]; P = .006) and more frequent corticosteroid exposure (35% [34 of 96] vs 24% [48 of 204]; P = .03) compared with nonchronic irAEs. For exploratory risk factor analysis of 300 nonendocrine irAE events, corticosteroid treatment and onset time had a significant interaction; corticosteroid-treated patients with earlier-onset irAEs had higher odds of developing chronic irAEs (odds ratio, 3.00; 95% CI, 1.45-6.22), adjusted for age, sex, and anti-PD-1 therapy continuation. Eight different cytokines had higher circulating plasma levels among patients with chronic irAEs after false discovery rate (FDR) adjustment (including VEGFA and CCL19), and 19 cytokines had significantly higher circulating plasma levels prior to FDR adjustment. No cytokine levels were higher among controls.

In this cohort study of patients with melanoma treated with adjuvant anti-PD-1 therapy, chronic irAEs were common, persistent, and associated with elevated circulating cytokines, suggesting possible candidate inflammatory pathways for future validation. Later irAE onset and corticosteroid-treated irAEs were associated with chronicity of irAEs. Given the long-term survival of these patients, monitoring and managing chronic irAEs is crucial.

Sex is a well-recognized factor associated with hepatocellular carcinoma (HCC) incidence, but its association with mortality is unclear.

To assess the association between sex and the risk of overall, liver-related, and non-liver-related mortality among patients with HCC.

This retrospective cohort study was conducted among patients with HCC in 17 centers from 5 countries and regions (2000-2023). Male and female patients with HCC who had balanced baseline characteristics via inverse probability of treatment weighting (IPTW) were included, with a propensity score-matched cohort included for sensitivity analyses. Data were analyzed between July 10 and September 8, 2025.

Male vs female sex.

Overall, liver-related, and non-liver-related mortality.

Among 8594 patients with HCC (mean [SD] age, 63.3 [10.9] years; 6214 male [72.3%]; 5644 Asian [65.7%], 458 Black [5.3%], 615 Hispanic [7.2%], and 1784 White [20.8%]), 4567 were from Asia (53.1%), 6327 had cirrhosis (73.6%), and 6617 had viral etiology (77.0%). In the unmatched cohort, males had a higher overall mortality rate per 100 person-years than females in the total cohort (15.9 [95% CI, 15.3-16.4] vs 13.3 [95% CI, 12.5-14.1]; P < .001) and in Asian (14.1 [95% CI, 13.5-14.7] vs 11.1 [95% CI, 10.3-12.0]; P < .001), Asia region (14.4 [95% CI, 13.6-15.2] vs 10.8 [95% CI, 9.9-11.8]; P < .001), cirrhosis (17.6 [95% CI, 16.9-18.3] vs 14.4 [95% CI, 13.5-15.4]; P < .001), and hepatitis B (13.6 [95% CI, 12.7-14.5] vs 10.0 [95% CI, 8.6-11.5]; P < .001) and C (15.8 [95% CI, 15.0-16.6] vs 13.4 [95% CI, 12.4-14.6]; P < .001) subgroups. In the IPTW-matched cohort, male sex was associated with increased overall mortality in the full cohort (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.05-1.23]; P = .002) and in Asian (aHR, 1.22 [95% CI, 1.10-1.36]; P < .001), Asia region (aHR, 1.23 [95% CI, 1.09-1.39]; P < .001), cirrhosis (aHR, 1.18 [95% CI, 1.08-1.29]; P < .001), and viral (aHR, 1.15 [95% CI, 1.05-1.26]; P = .004) subgroups. Additionally, sex differences varied by liver disease etiology, with male sex having the highest aHR in the association with overall mortality among individuals with alcohol-associated liver disease (aHR, 1.90 [95% CI, 1.02-3.54]; P = .04), followed by those with hepatitis B (aHR, 1.22 [95% CI, 1.01-1.47]; P = .04) or C (aHR, 1.13 [95% CI, 1.02-1.26]; P = .03), but there was no association in patients with metabolic dysfunction-associated steatotic liver disease. There was no significant sex difference for non-liver-related mortality.

In this study, sex disparities in HCC mortality existed but were heterogeneous across ethnic background and liver disease etiologies. These findings support incorporation of sex-based considerations in HCC management.

To summarize current imaging modalities for upper tract urothelial carcinoma (UTUC) and evaluate their diagnostic performance for tumor staging and risk stratification.

CT urography remains the diagnostic standard with excellent accuracy for tumor detection, though its reliability for local staging is limited. MR urography shows promise for assessing muscle invasion but is operator dependent. FDG-PET demonstrates value in nodal and metastatic staging rather than primary tumor evaluation. Retrograde pyelography maintains a role in tumor diagnosis in circumstances where cross-sectional imaging is unable to be performed. Emerging approaches, including radiomics and machine learning, as well as novel modalities such as endoluminal ultrasound, optical coherence tomography, and contrast-enhanced ultrasound show encouraging preliminary results but lack large-scale validation. No single modality provides accurate clinical staging in UTUC. A multimodal approach integrating imaging with clinical and endoscopic data remains essential, while emerging technologies may improve future risk stratification.

This review summarizes current evidence on interventional therapies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT), compares the treatment strategies between East and West, and proposes a practical framework for patient selection in the immunotherapy era of HCC.

Although systemic therapy remains the primary treatment for advanced HCC with PVTT, selected interventional therapies may provide additional value in carefully chosen patients with preserved liver function, liver-dominant disease, anatomically targetable PVTT, and adequate or reconstructable portal venous flow. Interventional options include transarterial chemoembolization, hepatic arterial infusion chemotherapy, transarterial radioembolization/selective internal radiation therapy, radiotherapy, portal vein stenting, and iodine-125 seed-based endovascular brachytherapy. Eastern and Western practice patterns differ mainly in the threshold for locoregional intensification, technical platform availability, and interpretation of the available evidence. Eastern and Western approaches increasingly share the principle that systemic therapy is the treatment backbone for advanced HCC with PVTT. The key clinical question is how interventional therapy should be integrated for selected patients rather than whether it should replace systemic therapy. Optimal management should be individualized through multidisciplinary decision-making based on PVTT extent, portal venous flow, liver function, intrahepatic and extrahepatic tumor burden, treatment goals, and institutional expertise. Future studies should standardize reporting of PVTT classification, portal vein patency, collateral circulation, liver reserve, tumor distribution, systemic therapy context, and treatment sequencing.

To evaluate whether structured exercise, compared with usual care, preserves left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and cardiac biomarkers in women with breast cancer receiving anthracyclines and/or anti-HER2 therapy.

We performed a systematic review and meta-analysis of randomized controlled trials. Risk of bias was assessed with the revised Cochrane risk-of-bias tool for randomized trials (RoB 2), and certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. When clinically and methodologically comparable, effects were pooled as net differences in change (ΔEG - ΔCG) using random-effects models. The primary synthesis was restricted to the baseline-to-end-of-anthracycline-treatment window (~ 4 months).

Seven trials (9 reports; n = 513) were included. Most trials had some concerns or high risk of bias. Quantitative synthesis was feasible in only two trials. No between-group differences were observed for LVEF (MD 0.07, 95% CI - 1.38 to 1.52; I² = 28.2%) or GLS (MD - 0.10, 95% CI - 0.79 to 0.58; I² = 0%). Confidence intervals were wide and compatible with benefit, no effect, or harm. Biomarker data were too heterogeneous for meta-analysis. Comparative clinical cardiovascular-event and survival outcomes and formal assessments of heart failure with preserved ejection fraction (HFpEF) were not reported.

Current randomized evidence is sparse, heterogeneous, and of low certainty. Available data do not confirm a consistent cardioprotective effect of exercise on LVEF or GLS and do not permit conclusions about clinical cardiovascular events, survival, or HFpEF.

Anxiety and emotional dysregulation remain among the most prevalent unmet supportive care needs in breast cancer survivorship, yet reported affective outcomes are strikingly inconsistent, with some survivors showing elevated distress and others displaying resilience or post-traumatic growth. Because distress screening in survivorship relies almost exclusively on self-report, the neural mechanisms shaping how chemotherapy-exposed survivors perceive and report emotional experience remain poorly understood, limiting mechanism-informed psychosocial support.

Forty female breast cancer survivors (27 chemotherapy-treated, 13 non-chemotherapy) and 30 age-matched healthy controls completed a validated face-word emotional Stroop task during functional MRI to probe emotional attention and conflict regulation. Standardized cognitive and affective questionnaires were aggregated into composite indices characterizing each survivor's neurobehavioral profile.

Chemotherapy-treated survivors showed poorer Stroop accuracy for faces normatively categorized as fearful and hypoactivation of the dorsomedial prefrontal cortex, yet reported lower affective symptoms than non-chemotherapy survivors, who instead showed heightened negative attentional bias and greater incongruency-related interference in the parahippocampal gyrus and insula. A normative inverse coupling between dorsal anterior cingulate cortex activation and affective symptom severity was present only in healthy controls.

Breast cancer survivors exhibit distinct neurobehavioral phenotypes with potential supportive care implications. Lower self-reported distress in chemotherapy-treated survivors paralleled reduced salience network engagement, a configuration compatible with emotional blunting rather than genuine well-being; because emotional blunting was not measured directly, this remains an interpretive hypothesis. These findings caution against relying solely on self-report screening and motivate the hypothesis that treatment-history-informed survivorship care may be beneficial-affective re-engagement strategies for chemotherapy-exposed survivors, and attention-bias modification or mindfulness-based approaches for non-chemotherapy survivors-a proposal that now requires testing in intervention trials.

To examine psychosocial and clinical factors associated with the intention to complete advance directives among patients with cancer undergoing treatment in South Korea.

Structured questionnaires assessed 200 patients receiving cancer treatment for their attitudes toward advance directives, subjective norm, perceived behavioral control, knowledge about advance directives, and cancer-related fatigue. Hierarchical multiple regression analysis was conducted in three steps: Step 1 included attitude and subjective norm (Theory of Reasoned Action); Step 2 added perceived behavioral control (Theory of Planned Behavior); and Step 3 incorporated knowledge and cancer-related fatigue (Extended Theory of Planned Behavior).

Attitude, subjective norm, and perceived behavioral control significantly predicted behavioral intention, explaining 74.1% of the variance. Perceived behavioral control had the strongest effect. Knowledge and cancer-related fatigue were not statistically significant.

These findings highlight the Extended Theory of Planned Behavior as a useful framework for understanding advance directive completion among cancer patients. Perceived behavioral control was identified as the strongest predictor of intention, underscoring the importance of enhancing patients' confidence and ability to engage in advance care planning. The results suggest that structured counseling and tailored education should be initiated early in the treatment process to support autonomous decision making that reflects patients' values and preferences for end-of-life care. Interventions that strengthen attitudes, foster supportive norms, and build perceived control may further promote advance directive planning.

Continuous and maintenance therapy remains central to multiple myeloma (MM) care, but repeated treatment-related healthcare encounters may impose physical, psychosocial, and logistical burden. We explored patient preferences regarding intervals between active treatment contacts, monitoring trade-offs, and opportunities to improve inpatient and outpatient care.

A 12-month, single-center mixed-methods survey was conducted among 100 patients with MM at a German tertiary center. The survey assessed the perceived importance and preferred length of treatment-free intervals (TFIs), monitoring perceptions, relapse-risk trade-offs, inpatient stressors, and care-improvement proposals. Quantitative responses were summarized with item-specific denominators and exact 95% confidence intervals (CIs). Free-text responses underwent inductive content analysis by two independent raters and mixed-methods integration.

Intervals between inpatient treatments were rated 10/10 by 49/100 participants (49.0%; 95% CI 38.9-59.2) and 0/10 by 9/100 (9.0%; 95% CI 4.2-16.4). The most frequently reported inpatient stressors were separation from family (27.0%), treatment-related symptoms or side effects (23.0%), and fatigue (17.0%). Regular check-ups were reassuring for 77/100 (77.0%; 95% CI 67.5-84.8) and burdensome for 13/100 (13.0%; 95% CI 7.1-21.2). Seven of 100 participants (7.0%; 95% CI 2.9-13.9) explicitly accepted higher relapse risk for longer TFIs. Preferred minimum interval length was heterogeneous; 39/99 (39.4%; 95% CI 29.7-49.7) preferred > 8 weeks. Qualitative narratives emphasized recovery, autonomy, restoration of routines, and modifiable care-process factors.

Patients frequently valued intervals between active treatment contacts for recovery, while monitoring was predominantly reassuring. These descriptive findings do not establish the safety or clinical appropriateness of longer TFIs but support prospective evaluation of preference-sensitive scheduling and monitoring.

Appetite loss is common during chemotherapy. However, its association with dietary intake and quality of life (QOL) in patients with gynecologic cancer remains unclear. This study aimed to clarify the dietary changes associated with appetite loss and investigate their association with QOL and adverse events.

Patients with gynecologic cancer receiving chemotherapy were enrolled in this single-center longitudinal observational study. Dietary intake was assessed at baseline and before the third chemotherapy cycle using a diet history questionnaire. Appetite loss, QOL, and adverse events were evaluated using the EORTC QLQ-C30 and PRO-CTCAE. Sensitivity analyses addressed pre-existing appetite loss and postoperative effects. A complementary analysis of a separate cohort examined the association between appetite loss and longitudinal QOL changes.

Among 105 patients, 41 (39.0%) reported appetite loss before the third chemotherapy cycle. The appetite loss group showed greater reductions in energy and macronutrient intake, whereas macronutrient composition did not differ between the groups. Absolute micronutrient intake broadly decreased, but no difference remained significant after energy adjustment. Among adverse events, taste changes were most closely associated with appetite loss. Appetite loss was also associated with QOL decline, and dietary findings were directionally consistent in sensitivity analyses. The complementary analysis showed appetite loss was consistently associated with QOL fluctuations.

Appetite loss during chemotherapy was associated with reduced dietary intake and lower QOL. Taste alterations were closely associated with appetite loss. These findings support appetite loss as a clinically relevant target for the supportive care of patients with gynecologic cancers.