• Evaluating the Impact of Therapeutic Anticoagulation Management in Head and Neck Free Tissue Transfer: A Retrospective Study of 126 Cases.
    5 days ago
    Existing literature on anticoagulation in head and neck free flap reconstruction largely focuses on postoperative thromboprophylaxis. Less is known about preoperative therapeutic anticoagulation, including how perioperative anticoagulation holds, timing of resumption, and anticoagulant class relate to hemorrhagic, thromboembolic, and flap-related complications. This study evaluates these outcomes in anticoagulated patients undergoing head and neck free flap reconstruction and compares complication rates with matched non-anticoagulated controls.

    A retrospective chart review was performed on patients who underwent free flap reconstruction between 2009 and 2023 and had been on therapeutic anticoagulation for over 1 month preoperatively. A matched control group of non-anticoagulated patients was included for comparison.

    126 anticoagulated patients (mean age 71.8 years, 75.4% male) were included. The most common indications for anticoagulation were atrial fibrillation (62.7%) and venous thromboembolism (30.2%). Anticoagulation medications included warfarin (49.2%), apixaban (36.5%), rivaroxaban (12.7%), and dabigatran (1.6%). Anticoagulation was stopped an average of 4.4 days preoperatively and resumed 7.8 days postoperatively. Hemorrhagic complications occurred in 14 patients (11.1%), including hematomas and unrelated bleeding. Thromboembolic complications occurred in 9 patients (7.1%), 6 of which resulted in flap failure. On matched cohort analysis, controls had lower odds of any complication (OR 0.41, 95% CI 0.21-0.81, p = 0.010), hemorrhagic or thromboembolic complications (OR 0.27, 95% CI 0.11-0.63, p = 0.003), and hemorrhagic complications specifically (OR 0.26, 95% CI 0.09-0.81, p = 0.020), while thromboembolic complication odds were not significantly different between groups (OR 0.47, 95% CI 0.15-1.44, p = 0.19).

    This study highlights the challenges of managing therapeutic anticoagulation in head and neck free flap surgery, where thromboembolic risk during interruption and hemorrhagic complications upon resumption point to the need for clearer guidelines. Evidence-based protocols are needed to replace discretionary practices and improve outcomes.
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  • Additive and Dose-Dependent Effects of Coenzyme Q10 Combined With Myoinositol on Insulin Resistance and Hyperandrogenism in Women With Polycystic Ovary Syndrome: A Retrospective Controlled Study.
    5 days ago
    Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, hyperandrogenism, and reproductive dysfunction. Myoinositol and coenzyme Q10 (CoQ10) have complementary metabolic and hormonal effects; however, the additive and dose-dependent effects of CoQ10 remain unclear. This study evaluated these effects in women with PCOS.

    In this retrospective study, 200 women with PCOS were assigned to four groups: myoinositol plus CoQ10 100 mg (n = 55), myoinositol plus CoQ10 200 mg (n = 55), myoinositol alone (n = 45), and untreated controls (n = 45). Fasting insulin, HOMA-IR, total testosterone, and menstrual cycle regularity were assessed at baseline and 6 months. Between-group differences were evaluated using multivariable regression analyses and sensitivity analyses.

    All treatment groups showed improvements in metabolic and hormonal parameters, with the greatest effects observed in the combination therapy groups. Myoinositol alone was associated with significant reductions in HOMA-IR (β = -0.219; p < 0.001) and total testosterone (β = -3.145; p < 0.001) compared with untreated controls. The addition of CoQ10 resulted in dose-dependent improvements, with 100 and 200 mg doses demonstrating progressively greater reductions in HOMA-IR (β = -0.308 and -0.571, respectively) and total testosterone (β = -2.847 and -5.325, respectively) (all p < 0.001). Multivariable regression analyses confirmed that both CoQ10 doses remained significantly superior to myoinositol monotherapy. Menstrual cycle regularity improved most in the MI + CoQ10 200 mg group (36.4%).

    Adjunctive CoQ10 supplementation with myoinositol provides significant and dose-dependent improvements in insulin resistance and hyperandrogenism in PCOS. The magnitude of reduction observed with 200 mg CoQ10 suggests potential clinical relevance, particularly in metabolically compromised patients. Prospective randomized studies are warranted to confirm these findings.
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  • Clinicopathologic Features and Survival Determinants of Hepatosplenic T-Cell Lymphoma: A Pooled Patient-Level Dataset Analysis.
    5 days ago
    Hepatosplenic T-cell lymphoma (HSTCL) is an ultra-rare, aggressive T-cell neoplasm for which evidence regarding prognosis and optimal therapy remains limited. We conducted a retrospective pooled patient-level analysis of 529 patients from 198 sources. The median age was 32 years, with 71.7% male. Hepatosplenomegaly and bone marrow involvement were present in 99.7% and 91.8% of evaluable patients, respectively. Among 436 patients with evaluable overall survival (OS), the median OS was 12.0 months, and the median progression-free survival was 5.0 months. Multivariable analysis demonstrated that hemoglobin less than 8 g/dL (HR 3.36, 95% CI 1.61-7.00; p = 0.0012) and underlying immunosuppression (HR 3.00, 95% CI 1.77-5.06; p < 0.0001) independently predicted inferior OS, while time-dependent stem cell transplantation (SCT) was associated with improved survival (HR 0.31, 95% CI 0.15-0.65; p = 0.0021). A provisional two-point score incorporating severe anemia and immunosuppression stratified patients into low-, intermediate-, and high-risk groups, with median OS of 26, 5, and 3 months, respectively (log-rank p < 0.0001; C-index 0.706). Platinum-containing first-line regimens were associated with lower mortality compared to CHOP-like therapy (HR 0.43, 95% CI 0.25-0.75; p = 0.003). The SCT survival association was consistent across complementary analyses. Nonresponsive, stable, or progressive disease at transplantation predicted inferior post-transplant survival compared to complete response (HR 2.84, 95% CI 1.32-6.10; p = 0.007). These findings identify severe anemia and immunosuppression as adverse prognostic features, support non-CHOP platinum-based induction and early SCT evaluation after disease control. However, because this is a retrospective pooled design, the treatment associations and the provisional prognostic score still require external validation.
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  • Diagnostic and therapeutic impact of genomic testing in neuroendocrine neoplasms.
    5 days ago
    Neuroendocrine neoplasms (NENs) are a diverse group of rare cancers with high heritability and limited treatment options for metastatic disease. Genomic testing guidelines for patients with NENs are limited to germline testing in high-risk individuals and tumour mutational burden (TMB) in a subset of patients. Here, we assess the prevalence of clinically actionable somatic variants using gene panel testing in the AACR GENIE database, and our real-world experience using additional genomic testing methodologies such as whole genome sequencing (WGS) and circulating tumour DNA sequencing for patients with NENs. The AACR GENIE database contained large panel data for 2,838 samples representing 26 different NEN subtypes. Of the samples, 19.1% had an OncoKB-defined actionable variant; however, only 1.6% were Level 1. TMB ≥ 10 mut/Mb was found in 21% of the assessable AACR GENIE cohort, mostly in NEC subtypes. Our institutional cohort of 30 patients was analysed using tumour-normal WGS in 24/33 testing episodes. Eight of thirty patients (27%) had variant-based clinical trial recommendations made. Seven of twenty-four WGS cases (29%) had clinically reportable germline variants identified. Circulating tumour DNA testing (n = 5/33) was used to sequence patients with uncontrolled hormone syndromes and when adequate tissue was not available. In selected patients with certain metastatic NET subtypes or NECs, our data support consideration of comprehensive tumour-normal genomic testing.
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  • Can We Diagnose Early Melanoma by Genomics?
    5 days ago
    Melanoma incidence has increased approximately 6-fold over the past 40 years, driven primarily by melanoma in situ and thin invasive melanomas, which are among the most subjective lesions to diagnose on histopathology. This review examines whether genomics clarifies the "gray zone" between benign and malignant pigmented lesions, or instead recasts existing histopathologic ambiguity in molecular terms, while also considering whether genomic classification shifts overdiagnosis upstream instead of resolving underlying diagnostic uncertainty. Across cytogenetic, mutation-based, and gene-expression platforms, current assays perform best in unequivocal melanoma-versus-nevus comparisons and lose accuracy in diagnostically ambiguous lesions where clarification is most needed. Gene expression profile (GEP) tests can be useful diagnostic aids in tissue-rich equivocal lesions, including atypical Spitz tumors, MELTUMPs, and cellular blue nevus/blue nevus-like melanocytoma differentials. One clinicopathologic-genomic model, the Merlin CP-GEP test, has been prospectively validated for predicting sentinel lymph node status and is now recognized as supporting sentinel lymph node biopsy decisions in T1b/T2a melanomas. Importantly, a low-risk prognostic GEP class assignment should not displace the standard sentinel lymph node biopsy discussion. GEP tests are least useful for small, thin, equivocal junctional proliferations, precisely the lesions that are most difficult to diagnose. Pre-biopsy non-invasive assays carry the additional risk of lowering, rather than raising, the biopsy threshold. Overall, current genomic tools should be viewed as an adjunct to, rather than a replacement for, histopathology and clinical context.
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  • Phytochemical Profiling, Antioxidant Activity and Cytotoxic Potential of Chloroxylon swietenia DC. Stem Extracts Against Bladder Cancer Cell Lines.
    5 days ago
    Chloroxylon swietenia DC. is traditionally used in herbal medicine and is known to contain various secondary metabolites with pharmacological activities. This study includes qualitative and quantitative analysis of phytochemicals, antioxidant and anticancer potential of C. swietenia stem extracts. Stem extracts were prepared with chloroform, acetone, methanol and water. Phytochemical analysis revealed secondary metabolites, extracts were further analysed for total phenolic and flavonoid content, and bioactive compounds were identified by GC-MS analysis. Antioxidant activity was tested using total antioxidant capacity, DPPH and FRAP assays. Cytotoxicity was assessed on T24 cells using MTT. Methanol extract revealed the presence of flavonoids, glycosides, phenolics, saponins and tannins; acetone extract revealed the same presence of same secondary metabolites except saponins, leaving methanol extract with the highest diversity. Acetone had higher TPC (90.876 ± 0.964 mgGAE/g), whereas methanol had higher TFC (122.115 ± 0.962 mgQE/g). GC-MS identified the highest compounds in acetone. The highest total antioxidant capacity was 1.33 ± 0.02 (acetone). The methanol extract exhibited significant DPPH-scavenging activity with an IC50 of 119.080 μg/mL. Ferric reducing power was highest for methanol (0.75 ± 0.01). Acetone was most cytotoxic to T24 cells (IC50 17.131 μg/mL), followed by chloroform, aqueous and methanol. This study finds the presence of bioactive compounds in C. swietenia stem, which are potential natural sources with antioxidant and anticancer properties for further research.
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  • Exploring the Therapeutic Potential of Ginkgo biloba: Phytochemical Composition, Antibacterial Activity Against Multidrug-Resistant Pathogens, and Modulation of Cancer Signaling.
    5 days ago
    Evaluate the phytochemical composition of Ginkgo biloba methanolic extract and investigate its anticancer and antibacterial activity, along with exploring its potential molecular mechanism of action through molecular docking analysis.

    Phytochemical protocols including phenols, flavonoids and saponins were qualitatively evaluated. The anti-bacterial activity was tested versus G+ and G- bacteria using agar well diffusion method. Cytotoxic activity was investigated using the MTT assay on HepG2 (liver cancer), A549 (ling cancer) and WRL-68 (normal) cell lines. Additionally, molecular docking analysis was performed to evaluate the interaction between selected bioactive compounds and the Akt1 protein (PDB ID:2C6T).

    The extract demonstrated high levels of total phenols (309.47 ± 4.21 mg GAE/g), total flavonoids (299.78 ± 14.81 mg/mL), and total saponins (137.76 ± 1.72 g/100 g). A significant antibacterial activity was observed in a concentration-dependent manner; the strongest effect was against Escherichia coli, showing inhibition zones ranging from 10 to 27 mm. The MTT assay showed a dose-dependent reduction in the viability of cancer cells, where HepG2 viability decreased from 92.28 ± 1.88% to 45.48 ± 2.61% (IC50 = 144.8 µg/mL), and A549 viability decreased from 93.17 ± 0.41% to 56.16 ± 3.56% (IC50 = 54.33 µg/mL). Meanwhile, lower cytotoxicity was observed in normal WRL-68 cells (IC50 = 145 µg/mL). Molecular docking analysis revealed favorable binding of Ginkgo phytochemicals to the Akt1 active site, with ginkgolide B showing the highest binding affinity (-7.19 kcal/mol), followed by isorhamnetin (-6.79 kcal/mol).

    Ginkgo biloba methanolic extract demonstrates significant antibacterial, antioxidant, and anticancer activities. These biological activities mostly arise from its rich phytochemical composition, particularly the bioactive constituents that may target key signaling pathways such as PI3K/Akt. Consistently, molecular docking analysis suggests a synergistic multi-compound mode of action, supporting the idea that Ginkgo biloba has the potential to serve as a valuable source for multi-target therapeutic development.
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  • Optimizing Antimicrobial Treatment to Cryopreserve and Establish Oral Squamous Cell Carcinoma In-Vitro Models Derived from Habitual Tobacco Chewers.
    5 days ago
    Cryopreservation and establishment of reliable in vitro models of oral squamous cell carcinoma (OSCC) are frequently compromised by microbial contamination arising from the oral microbiota of habitual tobacco users. This study aimed to optimize an antimicrobial strategy prior to biobanking to eliminate resistant microbial contaminants and improve the reliability of OSCC primary cultures.

    OSCC tissues obtained from habitual tobacco chewers were subjected to either conventional penicillin-streptomycin (Pen-Strep) treatment or a stepwise antimicrobial treatment before cryopreservation. The optimized protocol employed a combination of cell culture-grade antibiotics to selectively eliminate Pen-Strep-resistant microbial taxa. Post-thaw tissue viability and epithelial outgrowth were assessed. Microbial profiling of conventionally treated tissues was performed using 16S and 18S rRNA gene sequencing, and antibiotic susceptibility testing was carried out to determine resistance profiles.

    Conventional Pen-Strep treatment alone was insufficient to eliminate microbial contamination, whereas the stepwise antimicrobial treatment effectively eradicated resistant microorganisms, enabling sterile tissue preservation. Post-thaw assessments demonstrated epithelial-like outgrowth from day 3 onward, confirming preserved tissue viability and integrity. Microbial profiling identified contaminants including Neisseria elongata, Streptococcus gallolyticus, and Candida albicans. Antibiotic susceptibility testing highlighted the necessity of tailored combinatorial antimicrobial strategies to overcome resistance.

    The refined biobanking protocol integrating a stepwise antimicrobial strategy prior to cryopreservation effectively mitigates microbial contamination while preserving OSCC tissue integrity. This approach enhances the reliability of OSCC primary cultures derived from tobacco chewers and provides a robust platform for translational oncology research and personalized medicine.
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  • Open, Laparoscopic, Retropubic, or Robotic? A Network Meta-Analysis of Post-Prostatectomy Oncologic Outcomes and Health-Related Quality of Life in Localized Prostate Cancer Patients.
    5 days ago
    Prostatectomy remains a standard surgical treatment for localized prostate cancer, a malignancy with substantial global incidence and clinical impact in men. Its rapid adoption of surgical modalities has outpaced supporting evidence, resulting in limited consensus in reporting HRQoL and oncologic outcomes. This paper aims to compare the oncologic and Health-Related Quality of Life (HRQoL) outcomes of open (ORP), retropubic (RRP), laparoscopic (LRP), and robot-assisted radical prostatectomy (RARP) in patients with localized prostate cancer.

    A systematic search of MEDLINE/PubMed, Embase, Cochrane Library, and grey literature for randomised controlled trials and comparative studies was performed from database inception to November 2025. Risk of bias was assessed using RoB 2.0 and ROBINS-I. A network meta-analysis evaluated oncological outcomes that consist of Biochemical Recurrence (BCR) and Positive Surgical Margins (PSM), and HRQoL metrics including urinary incontinence and erectile dysfunction. Ranking probabilities were estimated using Surface Under the Cumulative Ranking (SUCRA) values.

    Thirty-three studies that met the inclusion criteria were included involving 69986 patients. Overall risk of bias for both randomized and observational studies was low. RARP ranked highest for oncologic outcomes, demonstrating the greatest likelihood of minimizing BCR (SUCRA 84.2%; 14 trials, 17,932 patients) and PSM (SUCRA 93%; 29 trials, 38,509 patients). For HRQoL, non-robotic techniques were favored across specific domains: ORP showed a 76% probability of fewer urinary incontinence events; LRP demonstrated an 87% likelihood of requiring fewer pad changes; and RRP demonstrated a 95% probability of being the best-tolerated technique regarding postoperative erectile dysfunction.

    RARP appears as the most favourable oncological outcome, whereas non-robotic approaches showed advantages in HRQoL domains. Future randomized trials are needed to prove the superiority of the techniques.
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  • In Silico Study of Micheliolide Derivatives as Potential Non-Small Cell Lung Cancer Drugs Targeting the Epidermal Growth Factor Receptor.
    5 days ago
    To identify Micheliolide-based derivatives with favorable drug-like properties and inhibitory potential against the epidermal growth factor receptor (EGFR) using an integrated in silico approach.

    Micheliolide derivatives were evaluated for pharmacokinetic and toxicity profiles using SwissADME and ADMET-AI, and anticancer-related activity was predicted using PASS Online. Molecular docking was performed with AutoDock Vina using erlotinib as a reference ligand. The top-ranked compounds were further examined through 50 ns molecular dynamics simulations to assess complex stability.

    All derivatives fulfilled Lipinski's criteria. Several compounds demonstrated favorable predicted bioavailability and anticancer probability. Docking analysis identified compound 10 as having the strongest binding affinity, followed by compounds 19 and 3, with all three occupying the same EGFR binding pocket as erlotinib. Molecular dynamics simulations showed that compounds 3 and 19 formed more stable complexes, maintaining root-mean-square deviation values of approximately 1-3 Å throughout the trajectory, whereas compound 10 displayed greater fluctuations and reduced stability.

    Compounds 3 and 19 exhibited the most favorable combination of binding affinity, dynamic stability, and predicted safety profiles, highlighting their potential as lead candidates for further development as EGFR inhibitors in NSCLC.
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