Journal of the Chinese Medical Association : JCMA最新文献

Background: The Montreal Cognitive Assessment (MoCA) may not be appropriately interpreted in Taiwan because of the lack of large-scale normative data. Moreover, examinees' demographic characteristics may influence their MoCA scores. However, previous studies have not adequately adjusted for these effects. This study aimed to use regression-based methods to establish demographically adjusted MoCA norms.

Methods: Participants were recruited from six hospitals and neighboring communities from all geographic areas of Taiwan. Multiple regression analyses were conducted to quantify the effects of age, education, and sex on MoCA total and domain scores, resulting in correction equations and adjusted cutoff scores.

Results: A total of 2310 cognitively healthy participants were included in the analysis. Age and education significantly affected the total and all domain scores. Sex affected naming, language, and abstract thinking domain scores. Correction equations and corresponding cutoffs were proposed for MoCA total and domain scores to support more precise clinical interpretations.

Conclusion: This study provides regression-adjusted norms for the MoCA, improving its accuracy and clinical utility in Taiwan. An adjusted total MoCA score of 23 points is recommended as the cutoff for identifying potential cognitive impairment, with domain-specific cutoffs further supporting individualized interpretation.

Background: Since 2018, Taipei Veterans General Hospital (TPEVGH) has performed endovascular thrombectomy (EVT) on acute ischemic stroke patients air-transferred from Kinmen Hospital (KMH). This study evaluated the clinical profiles and outcomes of these patients, comparing them to those treated directly at TPEVGH.

Methods: In this retrospective study, we included consecutive acute ischemic stroke patients air-transferred from KMH to TVGH for EVT between January 2018 and April 2024. A comparison group comprised patients who presented directly to TVGH and underwent EVT during the same period. Transfer decisions at KMH were based on clinical presentation and neuroimaging evidence of large vessel occlusion. Only patients with salvageable brain tissue (substantial penumbra without a large infarct core) were transferred. Exclusion criteria included a premorbid modified Rankin Scale (mRS) score ≥3, in-hospital stroke, serious advanced illness, or life expectancy <6 months. Primary outcomes were 90-day functional independence (mRS 0-2), 30-day mortality, and symptomatic intracranial hemorrhage (sICH). Analyses included Mann-Whitney, χ 2 tests, and multivariate logistic regression.

Results: A total of 275 patients were included: 15 from KMH (mean age 71.1 ± 11.7 years; 40% male; median National Institutes of Health Stroke Scale [NIHSS] 15) and 260 from TVGH (mean age 73.5 ± 13.6 years; 53% male; median NIHSS 18). KMH patients had longer onset-to-door times (median [interquartile range {IQR}] = 452.0 [400.0] vs 217.0 [442.8] minutes; p < 0.001] but shorter door-to-puncture times (121.5 [43.5] vs 144.0 [55.3] minutes; p = 0.031). Among KMH patients, the substantial reperfusion rate was 73.3%, 90-day functional independence was 40.0%, sICH rate was 13.3%, and 30-day mortality was 13.3%, outcomes comparable to those of TPEVGH patients.

Conclusion: Despite longer transfer times, air-transferred patients achieved similar safety and efficacy outcomes after EVT compared with directly treated patients. Further studies are warranted to optimize transfer strategies and patient selection.

Background: Immune checkpoint inhibitors (ICIs) have demonstrated survival benefits when combined with platinum and etoposide (EP) in first-line (1L) treatment for extensive-stage small-cell lung cancer (ES-SCLC). We investigated the real-world outcomes, adverse events (AEs), and prognostic factors of Taiwanese patients with ES-SCLC receiving 1L ICI + EP.

Methods: We analyzed the clinical characteristics, objective response rates, disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related AEs of patients with ES-SCLC who received ICI + EP or EP alone as 1L treatment.

Results: A total of 33 patients received ICI + EP, and 199 received EP alone. The 1L ICI + EP group had longer OS than did the 1L EP group (median: 13.9 months vs 8.5 months; p = 0.003). Baseline liver metastasis was associated with shorter 1L PFS, whereas undergoing consolidative thoracic radiotherapy (cTRT) was associated with longer 1L PFS. Baseline liver metastasis, severe hematological AEs (grade ≥ 3), and a neutrophil-to-lymphocyte ratio (NLR) of ≥4 were associated with shorter OS.

Conclusion: Adding ICIs to 1L chemotherapy provides survival benefits in ES-SCLC, while close monitoring for AEs is required. cTRT enhances local tumor control and improves PFS. Liver metastasis is associated with shorter PFS and OS. Severe hematological AEs and an elevated NLR predict poor OS in patients with ES-SCLC undergoing immunochemotherapy.

Background: Breast cancer is a leading cause of cancer-related deaths in women, particularly those with the triple-negative (TN) phenotype. Although novel therapeutic options are emerging, most are biomarker-driven. This study used comprehensive genomic profiling (CGP) via targeted sequencing to identify actionable alterations in a TN subcohort of the VGH-TAYLOR study.

Methods: The study included patients with either early-stage (defined by first-line surgery or neoadjuvant therapy) or late-stage (defined by relapse or de novo metastatic disease) breast cancer. CGP was performed using the Illumina TruSight Oncology 500 assay. The level of actionability was assessed using the European Society for Medical Oncology (ESMO) Scale of Clinical Actionability of Molecular Targets (ESCAT) criteria, with additional annotations provided by the PierianDx software and OncoKB database.

Results: CGP was successfully performed on 104 TN breast cancer samples. The most common actionable genes (occurring in >10% of cases) were PIK3CA (38%), BRCA2 (25%), PTEN (13%), BRCA1 (13%), ERBB2 (12%), and ERBB3 (11%). After applying a stringent per-variant filter, these frequencies were reduced to 22%, 6%, 5%, 4%, 4%, and 1% for PIK3CA , PTEN , BRCA2 , BRCA1 , AKT1 , and PALB2 , respectively. Based on the standard cut-off of 10 mutations/megabase, 24 samples were classified as tumor mutation burden (TMB)-high, whereas 80 were TMB-low. The proportion of TMB-high cases was lower among the early-stage patients compared to the late-stage patients (19% vs 36%; p < 0.05).

Conclusion: This study demonstrates the clinical feasibility and utility of large-scale CGP, enabling the investigation of a broad range of genes and multi-gene signatures, such as TMB and microsatellite instability (MSI). The identification of actionable biomarkers offers the potential to expand therapeutic opportunities for TN breast cancer patients.

Background: The study aimed to examine the relationship between retinal microcirculation, brain white matter hyperintensities (WMH) seen on magnetic resonance imaging (MRI), and cognitive decline in asymptomatic carriers of NOTCH3 mutations, a preclinical stage of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Methods: Forty-nine asymptomatic carriers without stroke history or cognitive complaints were studied. Retinal vessel density and WMH volume were measured via optical coherence tomography angiography and MRI, respectively. Cognitive function was assessed using various tests.

Results: In a multivariable regression model which included both, the whole brain WMH volume and parafoveal vessel density of superficial retinal plexus (SRP) as independent variables, parafoveal vessel density of SRP emerged as a significant predictor for Montreal Cognitive Assessment (MoCA) score ( β = -0.31; 95% confidence interval, -0.1516 to -0.0002; p = 0.044) in this cohort, and consistent findings were observed for Color Trails Tests (CTT)-1 and CTT-2 scores.

Conclusion: In asymptomatic NOTCH3 mutation carriers, higher parafoveal vessel density of the SRP may serve as an indicator of cognitive decline, and may also indicate autoregulatory compensatory mechanisms in response to a dysfunctional capillary plexus, potentially signifying early-stage cognitive decline.

Background: Genetic studies have identified more than 100 loci linked to major depressive disorder (MDD), underscoring its polygenic characteristics. Although the protein polybromo-1 ( PBRM1 ) rs2251219 polymorphism was reported to be associated with MDD, this has not been corroborated by additional studies. In the present study, the associations between PBRM1 rs2251219, MDD, and key biochemical variables were evaluated in a large Taiwanese cohort.

Methods: Data were collected from 117 679 individuals aged 30 to 90 years who were enrolled in the Taiwan Biobank. MDD diagnoses were based on self-reported data validated through national insurance claims records. Genotyping was conducted with an Axiom Genome-Wide Array, and associations with biochemical variables were analyzed through a general linear model adjusted for age and sex.

Results: A significant association was observed between PBRM1 rs2251219 and MDD risk ( p = 0.021 for genotype and p = 0.025 for allele). Individuals with the T allele had a higher MDD risk than C/C genotype carriers did. Biochemical differences were also observed, with T/T carriers with lower body mass index, platelet counts, albumin concentrations, and fasting glucose levels and higher red blood cell counts, hematocrit levels, and uric acid levels.

Conclusion: The PBRM1 rs2251219 polymorphism was associated with both MDD and biochemical measurement variation. These findings support the effects of the PBRM1 rs2251219 polymorphism on blood protein levels and psychiatric traits.

Background: Electroacupuncture (EA) is a form of physical therapy rooted in traditional Chinese medicine, which has been widely used in clinical practice. This study aimed to explore the effect of EA treatment on synaptic plasticity in mice subjected to middle cerebral artery occlusion (MCAO) and to elucidate the associated molecular mechanisms.

Methods: After MCAO modeling, C57BL/6 mice underwent EA treatment and/or miR-670-3p mimic injection, followed by assessment of neurological deficit by modified neurological severity score (mNSS) and cerebral infarction areas were evaluated via TTC staining. The changes of synaptic ultrastructure related parameters were observed using transmission electron microscopy (TEM). The expression levels of miR-670-3p, HMGB1, TLR4/NF-κB pathway-related proteins, and synapse-associated proteins (Synapsin I, PSD95, BDNF, and GAP43) were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The binding relationship between miR-670-3p and HMGB1 was assessed through dual-luciferase reporter assays and RNA pull-down assays.

Results: Mice that underwent EA treatment or miR-670-3p mimic injection exhibited increased miR-670-3p expression, reduced expression levels of HMGB1 and TLR4/NF-κB pathway-related proteins, improved neurological function, and enhanced synaptic plasticity. Furthermore, the combination of EA treatment and miR-670-3p mimic injection produced a synergistic effect, further amplifying these outcomes. Mechanistically, miR-670-3p was found to negatively regulate HMGB1.

Conclusion: EA treatment enhances synaptic plasticity in MCAO mice by promoting miR-670-3p expression to negatively regulate the HMGB1/TLR4/NF-κB pathway.