Journal of the Chinese Medical Association : JCMA最新文献

Background: This study aimed to establish a targeted fetal next-generation sequencing (NGS) panel and evaluate its diagnostic yield in sonographically normal fetuses.

Methods: A retrospective analysis was conducted on 1,820 cases of sonographically normal fetuses who underwent fetal NGS targeted panel testing, based on parental requests, between June 2021 and June 2023.

Results: Among the 1,820 cases analyzed, 833 cases (45.8%) showed no anomalies, 893 cases (49.1%) were identified with abnormal carrier statuses, and 94 cases (5.2%) exhibited pathogenic condition. The most frequently identified condition was glucose-6-phosphate dehydrogenase (G6PD) deficiency, with hemizygous mutations observed in 35 cases. This was followed by homozygous pathogenic variants in the GJB2 gene, identified in 19 cases. Additionally, 83 cases exhibited G6PD gene mutations, and 344 cases were identified as carriers of GJB2 gene variants. Other notable findings included 15 cases of familial hypercholesterolemia, 5 cases of Noonan syndrome, and 2 cases of osteogenesis imperfecta. Rare disorders identified were Wilson's disease, cystic fibrosis, Cockayne syndrome, and ototoxic hearing loss, each occurring in a single case.

Conclusion: The study demonstrated that the fetal NGS targeted panel yielded critical findings in 5.16% of sonographically normal fetuses, emphasizing its potential in prenatal diagnostics. Effective screening requires careful variant selection and detailed pre- and post-test genetic counseling to ensure clinical relevance and informed decision-making for parents.

Small bowel bleeding, accounting for 5-10% of gastrointestinal bleeding episodes, presents a distinct diagnostic challenge due to the organ's length and anatomical complexity. Over recent years, the management of small bowel bleeding has significantly evolved, driven by advancements in both diagnostic and therapeutic technologies. This Taiwan association for the study of intestinal diseases (TASID) practical consensus integrates local epidemiology, up-to-date diagnostic advances including early small bowel capsule endoscopy, and emerging treatments for vascular lesions like angiodysplasia. This practical consensus is divided into four major parts, including: I. terminology regarding small bowel bleeding and differential diagnosis II, evaluation of suspected small bowel bleeding III. endoscopy for small bowel bleeding and IV. medical treatment. Clinicians should be equipped to identify common causes of small bowel bleeding, understand the advantages and limitations of various evaluation methods, and apply a stepwise, evidence-based approach in managing these patients.

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: The clinical significance of programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC), particularly its association with platinum resistance (PR) and prognosis, remains unclear. This study aimed to evaluate the relationship between PD-L1 expression and PR in EOC and investigate cisplatin-induced PD-L1 modulation using in vitro and in vivo models.

Methods: We retrospectively analyzed 189 patients with EOC, treated between 2014 and 2020. Tumor PD-L1 expression was assessed by immunohistochemistry (IHC) using the combined positive score (CPS). Serum PD-L1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Cisplatin-induced PD-L1 regulation was examined in paired platinum-sensitive (PS: A2780 and ES2) and PR (A2780R and ES2R) cell lines and xenograft models.

Results: High tumor PD-L1 expression (CPS ≥10) was more frequent in PR (38.5%) than in PS patients (19.0%, p < 0.01), and was associated with higher recurrence rates ( p < 0.001) and shorter overall survival ( p < 0.001). Serum PD-L1 concentrations were significantly elevated in patients with endometrioid and clear cell histologies compared with those in the control group ( p < 0.05). In vitro, PD-L1 expression was upregulated in PR cell lines compared with parental PS cell lines and was further increased following cisplatin exposure in a dose- and time-dependent manner. Xenograft models confirmed that cisplatin induces PD-L1 upregulation in both tumor tissue and serum, with more pronounced effects observed in PR tumors.

Conclusion: PD-L1 upregulation (CPS ≥10) is associated with PR, disease recurrence, and poor prognosis in EOC. Endometrioid and clear cell histologic subtypes demonstrated higher baseline PD-L1 expression in our cohort. Cisplatin-induced PD-L1 upregulation represents a tumor-intrinsic response, particularly in PR tumor cells, highlighting PD-L1 as a histology-specific marker of poor prognosis and a potential therapeutic target in platinum-resistant EOC.

Background: Single-large hepatocellular carcinoma (SLHCC) is defined as a solitary tumor that is >5 cm and lacks macrovascular invasion or extrahepatic spread. SLHCC is a distinct clinical subtype with considerable prognostic heterogeneity, and available staging systems offer limited predictive accuracy for this subgroup. Therefore, we aimed to develop a machine learning (ML)-based decision-tree model to improve individualized prognostic stratification of SLHCC.

Methods: This retrospective study included patients with SLHCC who were diagnosed at Taipei Veterans General Hospital between January 2012 and January 2023. The patients were randomly assigned to a training cohort and a validation cohort. Prognostic factors for overall survival (OS) were identified using multivariate Cox regression and incorporated into a decision-tree algorithm. The model performance was evaluated using accuracy and the area under the receiver operating characteristic curve (AUROC).

Results: Among the 477 patients, 307 (64.4%) received curative treatment, and 170 (35.6%) received non-curative therapy. The median age was 70 years, and 77.1% were male. After a median follow-up of 50 months, the 5-year OS rate was 42.0%. Six variables were independently associated with OS: tumor size >10 cm, serum creatinine >1 mg/dL, non-curative treatment, albumin-bilirubin (ALBI) grade 2, fibrosis-4 (FIB-4) score ≥2.67, and serum alpha-fetoprotein (AFP) >20 ng/mL. The decision-tree model incorporated four key variables: treatment modality, creatinine, tumor size, and FIB-4. The model stratified patients into five risk groups. The model's accuracy was 74.3% in the training cohort and 67.1% in the validation cohort, and the AUROCs were 0.756 and 0.706, respectively.

Conclusion: The clinically interpretable ML-based decision-tree model effectively stratifies patients with SLHCC according to prognosis using routine clinical and laboratory data. This model complements conventional staging systems and could support personalized treatment planning and patient counseling in real-world clinical practice.

Background: While clinical trials have established the non-inferiority of faricimab compared to aflibercept regarding 1-year visual acuity, real-world evidence directly comparing their early effects on anatomical changes remains limited. This study aimed to compare the early effects of these treatments in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV).

Methods: This retrospective study included treatment-naïve nAMD patients who received three monthly intravitreal injections of 6.0 mg/0.05 ml faricimab or 2.0 mg/0.05 ml aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), and subretinal hyperreflective material (SHRM) were assessed monthly for 4 months.

Results: A total of 76 eyes of 76 patients (38 per group) were enrolled in this study. Baseline characteristics were comparable between the two groups, and there were no significant differences in BCVA, CMT, SFCT, SRF, and IRF at 4 months ( p > 0.05). However, the faricimab group had significant improvements in BCVA at months 2, 3, and 4 ( p < 0.05), while this was not seen in the aflibercept group. The decrease in mean logarithm of the minimum angle of resolution (logMAR) was from 0.78 ± 0.47 to 0.66 ± 0.65 in the faricimab group compared to 0.78 ± 0.41 to 0.72 ± 0.60 in the aflibercept group ( p = 0.348) at 4 months. Moreover, significantly fewer faricimab-treated patients had PED (67.6% vs 91.9%, p = 0.016), SHRM (32.4% vs 59.5%, p = 0.022), and HRF (52.9% vs 89.2%, p = 0.001) at 4 months.

Conclusion: Faricimab and aflibercept demonstrated comparable effects on BCVA, CMT, and SFCT. However, faricimab was associated with better early control of PED, SHRM, and HRF. Further prospective trials are needed to validate our findings.

Background: To provide an objective means of outcome assessment, we developed an innovative methodology to evaluate facial symmetry without defining an anatomical midsagittal plane. This study aimed to assess this novel methodology for evaluating zygomaticomaxillary complex (ZMC) symmetry.

Methods: Patients who underwent ZMC fracture reduction with available postoperative facial computerized tomography (CT) images were included in the study group. The control group comprised patients who underwent facial surgeries unrelated to ZMC fractures and had either pre- or postoperative facial CT images. Segmented 3D models reconstructed from CT images, including forehead and bilateral ZMCs, were mirrored, transposed, and analyzed using Hausdorff distance (HD) to quantify the maximum morphological and spatial deviation between the two sides. The 95th percentile HD values (HD95) were calculated to represent the top 95% of surface-to-surface distances between mirrored and contralateral ZMCs, serving as an objective measurement of symmetry.

Results: The study group included 21 patients (12 males, nine females), consisting of two with isolated ZMC arch fractures, 12 with ZMC complex fractures, and seven with ZMC fractures combined with orbital blow-out or Le Fort I fractures. The control group comprised 22 patients (13 males, nine females) without ZMC fractures, including six with mandible fractures, two with orbital floor blow-out fractures, 11 with parotid gland tumors, and three who had undergone rhinoplasty. The mean HD95 was significantly higher in the study group (3.48 ± 1.50 mm) compared with the control group (2.00 ± 0.76 mm) ( p = 0.0002).

Conclusion: This study demonstrated that the bilateral ZMC symmetry can be effectively and objectively assessed using a novel approach that combines mirroring, transposing, and HD analysis. This approach offers a quantitative tool that may enhance preoperative planning and postoperative evaluation.