Journal of the Chinese Medical Association : JCMA最新文献

Agitation is a frequently occurring and challenging neuropsychiatric symptom of Alzheimer's disease (AD) that substantially affects quality of life, caregiver burden, and healthcare utilization. Non-pharmacological interventions, especially trigger identification, environmental adjustments, and supportive activities, remain the first-line approach for treating agitation. Pharmacological treatment should be considered only when non-drug measures are insufficient or when agitation causes severe distress or safety risks. This consensus integrates evidence up to June 2025, the Taiwan Ministry of Health and Welfare approvals, and Taipei Veterans General Hospital expert opinion. Among the approved agents, brexpiprazole demonstrated the strongest evidence and most favorable safety profile. Risperidone and aripiprazole are effective, but require careful monitoring for cerebrovascular and extrapyramidal risks. Selected antidepressants, particularly citalopram and agomelatine, should be considered when safety is prioritized. Anticonvulsants, acetylcholinesterase inhibitors, and memantine have limited efficacy and should be reserved for refractory cases. Long-term or routine pharmacological use is not supported by current evidence. Future research should focus on identifying responsive patient subgroups, optimizing dosing strategies, and integrating medications into individualized, multidisciplinary care plans.

Background: Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally carries a poor prognosis. Although immunotherapies have improved outcomes for patients with high PD-L1 expression, treatment options remain poorly defined for those with low PD-L1 expression or those refractory to the EXTREME regimen (platinum-based chemotherapy plus cetuximab). To address this gap, we retrospectively evaluated the efficacy of the MEMOCLUB regimen (methotrexate, epirubicin, mitomycin-C, Oncovin, cisplatin, leucovorin, 5-fluorouracil, and bleomycin) for the treatment of platinum-refractory R/M HNSCC.

Methods: This retrospective cohort study, conducted at Taipei Veterans General Hospital, Taiwan, assessed the efficacy and safety of the MEMOCLUB chemotherapy regimen, administered with or without cetuximab, for platinum-refractory R/M HNSCC between 2015 and 2022. The study measured objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Statistical analyses were performed using Kaplan-Meier survival curves, log-rank tests, and the Cox proportional hazards model for identifying prognostic factors.

Results: A total of 124 patients were enrolled. The median PFS was 2.9 months and OS was 5.3 months. The ORR was 10.5%, with a corresponding disease control rate of 27.4%. In both univariate and multivariate analyses, cetuximab co-administration emerged as a significant prognostic factor for improved OS. Subgroup analysis revealed that cetuximab- naïve patients derived the greatest survival benefit from the addition of cetuximab to the MEMOCLUB regimen. Hematological effects were the most common adverse events, with anemia being the most frequent. No cases of Grade 3 or higher mucositis were reported.

Conclusion: The MEMOCLUB regimen is a feasible salvage therapy in refractory HNSCC, which demonstrates reasonable efficacy and tolerability. The addition of cetuximab significantly prolonged survival in cetuximab-naïve patients, suggesting that its co-administration is an advantageous strategy for this specific subgroup of platinum-refractory R/M HNSCC patients.

Background: The efficacy and safety of preservative-free timolol (PF-timolol; Anme®) versus preserved timolol (P-timolol; Timoptol-XE®) have not been compared in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: In this randomized, crossover, single-center study, patients received PF-timolol twice daily or P-timolol once daily for 6 weeks, followed by crossover to the alternate treatment for 6 weeks. The primary endpoint was change in intraocular pressure (IOP) between treatment groups. Secondary endpoints were tear film break-up time (TBUT), superficial punctate keratopathy (SPK) score, conjunctival hyperemia, systemic vital signs, and patient-reported symptoms.

Results: A total of 34 patients (mean age 58.1 years; male 50%) were enrolled. At baseline, mean IOP was 13.6±2.7 mmHg (right eye, OD) and 13.4±2.7 mmHg (left eye, OS). At week 6, PF-timolol led to a greater reduction in IOP in the OD versus P-timolol (-1.3±1.5 mmHg vs. -0.2±1.2 mmHg, p=0.004), whereas no significant difference was observed in the OS (p=0.08). At week 12, mean IOP did not differ between the two groups for both eyes. TBUT increased in the PF-timolol group but decreased in the P-timolol group (p=0.006), and the change from baseline favored PF-timolol (p=0.001). The SPK score decreased significantly more in the OD in the PF-timolol group than P-timolol group (-0.4±0.84 vs. 0.2±1.1; p=0.03). Systolic blood pressure (SBP), diastolic blood pressure, and heart rate (HR) remained stable throughout the study period, with reductions at week 6 that did not persist to the next follow-up (both P=0.04). Patient-reported symptoms were comparable between treatment groups during 12 weeks.

Conclusion: PF-timolol eye drops achieved a greater IOP reduction at week 6 but showed comparable efficacy to P-timolol by week 12, while providing additional advantages in ocular safety outcomes and subjective tolerability. PF-timolol offers an effective and safer option for glaucoma management, particularly in patients sensitive to preservatives.

Background: Boron neutron capture therapy (BNCT) is a targeted form of particle radiotherapy (RT) that better spares normal tissues than does conventional photon RT. We describe our experience with compassionate-use BNCT for locally recurrent nasopharyngeal cancer (rNPC) after prior radiotherapy.

Methods: Data from patients with rNPC who received BNCT outside of clinical trials at the Tsing-Hua Open-Pool Reactor between 2020 and 2024 were retrospectively analyzed.

Results: Ten patients (eight men and two women) with a median age of 54 years and recurrent stage T2-T4N0-N1 disease were included. The median radiation dose before BNCT was 70 (range: 70-124) Gy. For the initial BNCT session, the median average tumor dose was 16.4 (range: 11.7-25.1) Gy-Eq delivered in a single fraction. Two patients underwent a second BNCT session for residual or recurrent disease at 3 and 12 months after the first, respectively. The median follow-up period was 10.7 (range: 2.2-50.9) months. Overall, one complete response and one partial response were observed after one or two BNCT sessions among eight evaluable cases. The most common acute toxicities were low-grade mucositis and dermatitis. No cases of carotid blowout syndrome were reported. Temporal lobe necrosis occurred in one patient who received two BNCT sessions. The one-year overall survival rate was 44.4%, and the one-year progression-free survival rate was 33%. One patient survived for more than 4 years.

Conclusion: In this small cohort of patients with recurrent NPC, compassionate BNCT with moderate doses yielded a 25% response rate and one long-term survivor (4 years). Protocol modifications involving adjusted dose-fractionation schedules and combination with other treatment modalities in future prospective trials may improve the outcomes for recurrent NPC.

Background: Controlled ovarian hyperstimulation (COH) is commonly used to obtain large numbers of high-quality oocytes. However, elevated estrogen levels due to COH can disrupt uterine fluid metabolism and impair embryonic implantation. We investigated the effects and mechanisms of Bushen Huoxue recipe (BSHX) on COH-induced impairment of endometrial receptivity.

Methods: Female mice were randomly divided into the following five groups: control, model, BSHX-L, BSHX-M, and BSHX-H. In addition to the control group, the COH model was established by injecting mice in the other groups with 0.4 IU/g pregnant mare serum gonadotropin and 1 IU/g human chorionic gonadotropin. After successful mating, mice in the BSHX-L, BSHX-M, and BSHX-H groups were treated with 5.5, 11.0, and 22.0 g/kg respectively. Mice in the control and model groups were administered distilled water (10 mL/kg) daily via gavage. Embryo numbers were examined on embryo day 10 (D10). Serum estradiol and progesterone levels were measured using an enzyme-linked immunosorbent assay on D4. Endometrial morphology was analyzed using hematoxylin-eosin staining. The protein and gene expression of leukemia inhibitory factor (LIF), cystic fibrosis transmembrane regulator (CFTR), and epithelial sodium channel (ENaC) subunits were assessed using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction.

Results: BSHX treatment reduced superphysiological serum estradiol and progesterone levels, improved endometrial morphology during the implantation window, upregulated LIF, α-, β-, and γ-ENaC expression, and downregulated CFTR expression, thereby enhancing embryo implantation.

Conclusion: BSHX may improve assisted reproductive technology pregnancy rates by regulating sex hormones and uterine fluid balance to prevent COH-induced endometrial damage.

Background: Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy with few effective treatments. Although the KRAS gene has been implicated in the progression of thyroid cancer, its specific mechanism in ATC remains unclear. This study aims to reveal the impact of cancer-associated fibroblasts (CAFs) with KRAS overexpression on the malignant biological behavior of ATC.

Methods: The single-cell RNA sequencing (scRNA-seq) was used to analyze the KRAS expression profile of fibroblasts (Fibs) in ATC progression, including cell subpopulation identification, KRAS distribution across different cell types, and functional pathway enrichment. Paracancerous tissue fibroblasts (PTFs) and CAFs were co-cultivated with ATC cells, respectively, and were treated with KRAS inhibitor BI-2865. Western blot, colony formation assay, EdU staining, Transwell, and Annexin V-FITC/PI staining were used to analyze the effects of KRAS on the proliferation, migration, and invasion abilities of ATC cells, as well as its influence on downstream signaling pathways.

Results: In contrast to papillary thyroid cancer (PTC), the proportion of Fibs significantly increased in ATC, with KRAS observed to be highly expressed in Fibs. Further analysis revealed that Fib_KRAS+, which was highly expressed in ATC samples, did not show expression in PTC samples. In vitro cell experiments confirmed that CAFs with KRAS overexpression enhanced the proliferation, migration, and invasion of ATC cells and activated the downstream signaling pathway RAS/RAF/MAPK.

Conclusion: In summary, CAFs with KRAS overexpression play a crucial role in the malignant biological characteristics of ATC. Targeting KRAS may be a potential strategy to effectively curb the malignant progression of ATC.

Background: Detecting bucket-handle meniscal tears (BHMTs) on knee radiographs remains challenging. Advances in deep learning, particularly convolutional neural networks, have shown strong potential in medical image analysis. This study evaluated the feasibility and diagnostic accuracy of a deep learning model for detecting BHMTs on knee radiographs and compared its performance to orthopedic surgeons.

Methods: Knee radiographs, including anteroposterior (AP) and lateral (Lat) views, were collected from our institution and external hospitals. Radiographs were screened and labeled based on arthroscopic confirmation of the presence or absence of BHMTs. All images were cropped and standardized before analysis. In addition to AP and Lat inputs, composite images combining both views were generated. Separate models were trained for each group, evaluated on an independent test set, and the best-performing model was compared with interpretations by orthopedic surgeons.

Results: In total, radiographs from 406 patients at our institution and 90 patients from external hospitals were included. The composite radiographs input achieved the highest performance in distinguishing BHMTs from non-BHMTs, with an area under the receiver operating characteristic curve (AUC) of 0.844, a sensitivity of 74.4%, a specificity of 85.0%, a positive predictive value (PPV) of 82.9%, a negative predictive value (NPV) of 77.3%, a precision of 82.9%, and an F1 score of 78.4%. Overall, the model demonstrated higher diagnostic performance for BHMT detection compared with orthopedic surgeons.

Conclusion: This study demonstrates the potential utility of deep learning for detecting bucket-handle meniscal tears on knee radiographs.