Diabetes mellitus is a widespread metabolic disorder characterized by impaired glucose regulation. This study investigated the chemical composition and antidiabetic potential of Origanum majorana essential oil (EO) using integrated in vitro, in vivo, and computational approaches. GC-MS analysis identified 42 constituents representing 96.28% of the oil, with trans-thujone (33.30%), santolina triene (16.42%), and cis-verbenyl acetate (15.05%) as the dominant components. In vitro assays revealed strong inhibitory activity against carbohydrate-hydrolyzing enzymes, with IC₅₀ values of 3.68 µg/mL for α-amylase and 4.71 µg/mL for α-glucosidase, which were lower than those of the reference drug acarbose (11.17 and 9.68 µg/mL, respectively). In vivo evaluation in alloxan-induced diabetic rats demonstrated a significant reduction in fasting blood glucose levels from 1.47 ± 0.04 g/L in the diabetic group to 0.94 ± 0.03 g/L after EO treatment, accompanied by improvements in biochemical and histopathological parameters. Molecular docking identified several major EO constituents with strong binding affinities toward α-amylase and α-glucosidase, particularly cis-verbenyl acetate (-6.64 and -7.27 kcal/mol) and β-pinene oxide (-5.40 and -6.46 kcal/mol), exceeding the affinity of acarbose. ADMET analysis predicted favorable pharmacokinetic profiles and low toxicity risks for these compounds. Molecular dynamics simulations confirmed stable protein-ligand interactions, while MM-PBSA calculations supported strong binding free energies. Density functional theory (DFT) analysis further revealed moderate reactivity and enhanced stability in aqueous environments. Overall, the combined experimental and computational findings suggest that O. majorana EO, particularly its constituents cis-verbenyl acetate and β-pinene oxide, represents a promising natural source of antidiabetic agents warranting further pharmacological investigation.

Endoscopic pilonidal sinus treatment (EPSiT) has emerged as a minimally invasive treatment option for pilonidal disease (PD) in adolescents, yet its adoption has been limited by the need for specialized equipment. We developed a modified EPSiT technique using standard urological instruments, saline irrigation, and lateral positioning, which was introduced in 2019. This study provides a technical description of the modified approach and evaluates the outcomes compared with conventional open excision in a pediatric cohort.

We conducted a single-center retrospective cohort study of 113 pediatric patients treated surgically for PD between 2014 and 2023. Patients were divided into two cohorts: EPSiT (n = 48, 2019-2023) and open excision (n = 65, 2014-2018). Clinical data were collected from medical records for both groups and structured telephone interviews for patients undergoing EPSiT. Outcomes included operative time, hospital stay, recurrence, pain, and satisfaction.

Gender distribution was identical in both cohorts (29.2% male, 70.8% female). Operative times were similar between groups (35.8 versus 31.7 min; p = .307). EPSiT was associated with significantly shorter hospital stays (mean difference -2.55 days; 95% CI -3.10 to -2.00; p < .001). Recurrence rates were comparable (16.7% versus 15.4%; p = .808). Patient-reported outcomes were available for the EPSiT cohort only and indicated high cosmetic satisfaction and minimal analgesic use. Among patients undergoing EPSiT, 41.7% returned to school immediately after discharge, and most resumed normal activities within a few days.

This modified EPSiT approach is feasible and may increase accessibility in resource-limited settings, representing a less invasive treatment option for PD. Further prospective studies are needed to validate these findings and define the role of EPSiT in the treatment of pediatric PD.

To investigate the expression level of cytochrome b561 (CYB561) in endometrial carcinoma tissues and analyze its relationship with clinicopathological characteristics and patient prognosis.

Bioinformatic analysis was performed to assess CYB561 mRNA expression and its correlation with prognosis in endometrial cancer. Immunohistochemical staining was used to detect CYB561 protein expression in 195 endometrial carcinoma tissues and 40 adjacent normal endometrial tissues. The associations between CYB561 expression and clinicopathological parameters, as well as its impact on overall survival (OS) and disease-free survival (DFS), were analyzed.

CYB561 expression was significantly higher in endometrial carcinoma tissues compared to adjacent normal tissues (P < 0.001). Low CYB561 expression was significantly associated with advanced FIGO stage (P < 0.05). Moreover, patients with low CYB561 expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) (log-rank P < 0.001 for both).

CYB561 is up-regulated in endometrial carcinoma, and its high expression is associated with a more favorable prognosis, suggesting its potential role as a prognostic biomarker for endometrial cancer.

Indolent non-Hodgkin lymphoma (iNHL) is a chronic, incurable lymphoid malignancy with a slow course. In absence of symptoms, a 'watchful waiting' approach is often chosen. The emotional burden of uncertainty and monitoring may affect patients' psychological well-being. This study investigates the extent of psychological distress in iNHL patients and its relationship with sociodemographics, clinical characteristics, and quality of life.

A cross-sectional study was conducted among adults with histologically confirmed indolent B-cell or T-cell NHL, recruited via a regional Dutch hospital and the online patient platform CMyLife. Data were collected through self-administered online questionnaires, including sociodemographics, clinical characteristics, psychological distress (HADS) and quality of life (EORTC QLQ-C30/LG-NHL).

A total of 352 iNHL patients completed the questionnaires (response rate: 37.5%). The mean age was 69 years, 58.5% were male and psychological distress (HADS ≥ 13) was observed in 30.7% of participants. Distressed patients were more often female, less educated, more frequently in the period of watchful waiting, and had more medical comorbidities (p < .01). They reported significantly lower health-related quality of life (HRQoL) (mean 51.2 vs. 77.6) and a higher symptom burden. Psychological distress was strongly correlated with lower HRQoL (r = -.63). In hierarchical regression analysis, psychological distress was the strongest predictor of lower HRQoL (β = -0.605, p < .001).

Approximately one-third of iNHL patients experience psychological distress, significantly associated with female gender, a lower education level, a watchful waiting approach, medical comorbidities, and a lower HRQoL. This underscores the importance of attention for these factors during consultations.

As cancer survivorship rises, provision of information during cancer care is increasingly important, especially regarding potential impacts on patients' health-related quality of life. We sought to understand information needs patients had before initiating anti-cancer treatment using data from a qualitative study designed to examine appropriate recall periods in patient-reported outcome measures of physical function (PF). In this secondary analysis from the Patient Reports of Physical Functioning Study (PROPS) research program, we report on: What do patients wish they had known about their PF before starting treatment?

In this secondary analysis, we examined transcripts from PROPS to describe what patients wish they had known about their PF before starting treatment. We used qualitative content analysis to analyze 72 semi-structured transcripts conducted with adults with cancer who had undergone anti-cancer treatment in the previous 6 months. The purpose of this analysis was to identify categories of patient information needs.

Of the 72 participants, over half indicated a desire for additional information about their PF before starting treatment, including the impact of side effects/symptoms, such as pain and fatigue, on PF, or a better understanding of expectations for PF. Most of these participants reported PF limitations during the interview. The remaining participants reported feeling fully informed, with most reporting no PF limitations.

Patients are interested in learning about the impact of treatment on their PF, but the amount of detail desired varies. Providing personalized information may enhance shared decision-making, empower patients in self-management and treatment decisions, and support timely referrals to specialists. These findings highlight the need for tailored communication strategies in cancer care to better address patient concerns and improve overall treatment experiences.

Venetoclax plus hypomethylating agents (HMAs) is a standard therapy for older or unfit patients with acute myeloid leukemia (AML); however, some patients exhibit suboptimal responses, potentially associated with T-cell exhaustion. Our preclinical findings that statins enhance HMA efficacy by boosting anti-tumor T-cell responses prompted us to translate this strategy to the clinic. A multicenter phase II clinical trial (ChiCTR 2500111931) was conducted to evaluate the efficacy and safety of adding rosuvastatin to venetoclax and azacitidine (venetoclax-azacitidine) in older/unfit AML patients. After induction therapy with this triple combination, the cohort achieved a complete response (CR) rate of 55.5% and a composite complete remission (CRc) rate of 72.2%. Among patients who achieved CRc, 84.6% attained measurable residual disease (MRD) < 10^-3. With a median follow-up of 10 months, the median overall survival (OS) and relapse-free survival (RFS) were 18 and 14 months, respectively. Although no significant changes in lipid profiles were observed, multiparametric flow cytometry revealed significant reductions in PD-1⁺CD4⁺ T cells (p = 0.0137) and PD-1⁺CD8⁺ T cells (p = 0.0277) after therapy. In vitro experiments revealed that the addition of rosuvastatin diminished both early (PD-1⁺TIM-3⁻) and terminally (PD-1⁺TIM-3⁺) exhausted T cells, suggesting it prevents the development of T-cell exhaustion induced by venetoclax-azacitidine. Furthermore, functional assays confirmed that rosuvastatin addition significantly enhanced T cell cytotoxicity against leukemia cells. Collectively, our findings suggest that adding rosuvastatin to venetoclax-azacitidine shows preliminary clinical activity and acceptable safety, possibly by reducing T-cell exhaustion, thus supporting further study of this triple regimen in older/unfit AML patients.

Minimally invasive extended left hepatectomy (MI-ExLH) remains a technically challenging procedure that is not yet standardized.

We retrospectively reviewed cases of minimally invasive left hepatectomy (MI-LH) and MI-ExLH performed between 2018 and 2025 at a single institution. Surgical strategies were classified into three categories according to the tri-scenario-based MAICOHAN strategy (MHV-based Assessment and Involvement/non-involvement in Caudate-hilum-dependent Optimal extended left Hepatectomy Algorithmic Navigation): (1) the cranio-dorsal or cranio-ventral approach, selected depending on the tumor-middle hepatic vein (MHV) relationship, (2) the Arantius-first or caudate lobe resection approach, chosen based on caudate lobe involvement, and (3) the liver-transection-first or left-hepatic-duct-dissection-first approach, based on the tumor-left hepatic hilum relationship. We divided the cases into two groups-the MAICOHAN strategy group (MS group) and the non-MAICOHAN strategy group (non-MS group), where procedures were and were not performed according to the abovementioned scenarios, respectively.

Eleven MI-LH and 12 MI-ExLH cases were included (MS group, n = 11; non-MS group, n = 12). Operative time and length of hospital stay were significantly shorter in the MS group than in the non-MS group (262 vs. 376 min, p = 0.023; 6 vs. 9 days, p = 0.016). In the subgroup analysis restricted to MI-ExLH cases, the incidence of positive surgical margins was significantly lower in the MS group (0% vs. 50%, p = 0.046).

The tri-scenario-based MAICOHAN strategy provides a practical framework that may contribute to guiding surgeons in planning and performing MI-ExLH more safely and consistently.

A small subset of isocitrate dehydrogenase-wild-type (IDH-wt) glioblastomas (GBMs) initially present as nonenhancing, T2 FLAIR hyperintense cortical/superficial lesions on MRI, potentially leading to misdiagnosis on the initial imaging and hence delayed treatment. This study aimed to characterize the clinical and MRI features of nonenhancing IDH-wt GBMs to help radiologists in differentiating them from nonmalignant mimic diagnoses (eg, encephalitis). Additionally, the histologic, genomic, and survival profiles of nonenhancing GBMs were compared with those of enhancing GBMs.

Clinical and MRI features from 32 patients, each with nonenhancing and enhancing GBMs, and 16 patients with nonmalignant mimic differential diagnoses from a single institution and publicly available data set were retrospectively analyzed. Imaging features were reviewed using the Visually Accessible Rembrandt Images features and the split ADC sign. χ² tests and a binary logistic regression model were used to compare nonenhancing IDH-wt GBMs with nonmalignant mimics. Histopathologic and genomic analyses were performed on institutional cases. Overall survival between nonenhancing and enhancing GBMs was compared using Kaplan-Meier analysis.

No significant difference in age, clinical presentation, or duration of symptoms was found between nonenhancing GBMs and nonmalignant mimics. Imaging features favoring nonenhancing GBMs included a greater proportion of non-contrast-enhancing tumor (OR, 7.4), larger anterior-posterior tumor dimension (OR, 8.4), restricted diffusion (OR, 3.6), and eloquent brain involvement (OR, 3.0) while features favoring mimics included greater edema (OR, 0.07), infiltrative T1 FLAIR ratio (OR, 0.68), hemorrhage (OR, 0.76), satellite lesions (OR, 0.84), and the split ADC sign (OR, 0.89). The logistic regression model achieved a mean area under the receiver operator characteristic curve of 0.89 (SD, 0.20) (accuracy 0.84, sensitivity 0.91, specificity 0.70, and precision 0.88). Twelve of 18 nonenhancing GBMs lacked histologic evidence of necrosis or microvascular proliferation ("molecular GBMs"). Genomic profiles were similar between nonenhancing and enhancing GBMs. Median overall survival was nonsignificantly longer in nonenhancing GBMs compared with enhancing GBMs (39 versus 21 months, P = .078).

Nonenhancing GBMs demonstrate distinct MRI features that must be recognized for early diagnosis and differentiation from nonmalignant mimics. Nonenhancing GBMs demonstrated longer overall survival compared with enhancing GBMs, though they were not statistically significant.

Nivolumab plus ipilimumab (COMBO) is the standard treatment for asymptomatic melanoma brain metastases (MBM), but current guidelines do not provide specific recommendations for treatment discontinuation in responding patients. This study aimed to evaluate outcomes after COMBO discontinuation within 24 months and the role of continuing treatment beyond 24 months.

Patients with MBM treated with COMBO who discontinued treatment within 24 months for reasons other than disease progression or continued beyond this time point were retrieved. Overall survival (OS), objective response, progression-free survival (PFS) and toxicities were analyzed.

465 patients were included: 392 discontinued COMBO within 24 months, while 73 continued beyond 24 months. Treatment was discontinued due to complete response (CR, n=47), partial response (PR, n=45), stable disease (SD, n=12), toxicity after SD (n=59), toxicity after CR (n=99), or toxicity after PR (n=130). At multivariable analysis, the line of treatment (>first vs first: HR 2.65 (1.62-4.32)), the immune-related adverse events (irrespective of anti-tumor necrosis factor-alpha) (HR 0.18 (0.07-0.42)); COMBO discontinuation after CR (HR 0.15 (0.05-0.40)), or PR (HR 0.08 (0.03-0.26)), as well as stopping due to toxicity after CR (HR 0.14 (0.07-0.27)) or PR (HR 0.51 (0.32-0.82)), were associated with OS. Notably, at a median follow-up of 51 months (IQR 31-70), patients with CR/PR who discontinued COMBO within 24 months had PFS and OS comparable to those who continued treatment beyond this time point. 4-year OS exceeded 83% in patients discontinuing COMBO after CR, PR, or toxicity following CR, compared with 66.4% in those discontinuing due to toxicity after PR; median PFS was not reached in the former groups but was 18.6 months in the toxicity after PR group.

Discontinuation of COMBO within 24 months appears safe in patients with CR and in selected cases of PR, with no survival disadvantage versus prolonged therapy.

Chimeric antigen receptor (CAR) therapies have revolutionized cancer immunotherapy, particularly in hematologic malignancies, but their efficacy in solid tumors remains limited. Key barriers include tumor antigen heterogeneity, on-target/off-tumor toxicity, impaired trafficking, and an immunosuppressive tumor microenvironment.

We conducted a narrative review of preclinical and clinical studies investigating CAR-engineered innate and innate-like immune cells, including CAR-natural killer, CAR-γδ T, CAR-natural killer T (NKT), and CAR-macrophages, focusing on their biological features, therapeutic potential, and current clinical development in solid tumors.

These alternative platforms exhibit distinct advantages over conventional CAR-T cells, including reduced risk of severe toxicities, improved trafficking, overcoming antigen loss, and higher allogeneic potential. Emerging clinical data suggest favorable safety profiles, although limited persistence and variable efficacy remain key challenges. Advances in cell engineering, such as cytokine armoring and non-viral gene transfer, are further enhancing their therapeutic potential.

CAR-engineered innate and innate-like immune cells represent a promising next-generation strategy to overcome the limitations of conventional CAR-T therapies in solid tumors. Among these, CAR-NKT and CAR-γδ T cells may offer particular advantages for clinical translation, warranting further investigation in future trials.