Autistic symptoms influence functional outcomes in individuals at high clinical risk for psychosis (CHR-P) and in those with first-episode psychosis (FEP). Our recent findings suggest that these symptoms encompass both enduring trait-like and transient state-like features that improve with treatment over a 12-month period. This study aimed to clarify the long-term course of autistic and non-autistic symptoms by comparing individuals with high and low levels of autistic symptoms at the CHR-P and FEP over an extended 18-month period. Sixty-two participants who completed the 18-month follow-up assessment (CHR-P, n = 37; FEP, n = 25) were included. At baseline, the high autistic symptoms (HA) group exhibited a significantly greater severity of autistic symptoms, more severe non-autistic psychiatric symptoms, and lower global functioning than the low autistic symptoms (LA) group. Over the 12- and 18-month follow-up periods, both groups showed significant improvements in non-autistic psychiatric symptoms and global functioning, and the initial group differences in these domains were no longer statistically significant. In contrast, although the autistic symptoms in the HA group decreased over time, a significant difference in the PAUSS total scores between the HA and LA groups persisted throughout the follow-up. While non-autistic psychiatric symptoms and functional impairments are responsive to treatment, autistic symptoms in individuals with CHR-P and FEP may encompass both modifiable, state-like features, and stable, trait-like characteristics, persisting over an 18-month period. Further research is warranted to elucidate the underlying mechanisms and clinical implications of persistent autistic symptoms in early psychosis.
Metastatic colorectal cancer (mCRC) differs clinically based on RAS and BRAF mutations or DNA methylation. However, in mCRC, the prognostic value and biological characteristics of genome-wide DNA methylation status (GWMS) in each RAS/BRAF genotype is unknown. To clarify this, primary tumor samples from patients with informed consent in the phase III TRICOLORE study were collected, and RAS and BRAF mutations, immunohistochemical staining of mismatch repair-related proteins, comprehensive gene expression, and genome-wide DNA methylation were analyzed. The tumor samples were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Gene set enrichment analysis (GSEA) was conducted using microarray data. A total of 226 patients were included and classified into the RAS/BRAF wild-type (wt) (n = 125), RAS mutant (mt) (n = 87), and BRAF mt (n = 14), of whom 22 (17.6%), 30 (34.5%), and 14 (100%) had HMCC. HMCC exhibited significantly worse overall survival (OS) than that of LMCC in the RAS/BRAF wt group but not in the RAS mt group. In GSEA, RAS/BRAF wt HMCC was associated with microsatellite instability and BRAF V600E mutation. The poor prognosis of RAS/BRAF wt HMCC may be attributed to gene expression patterns associated with microsatellite instability and BRAF V600E mutation.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
BACKGROUND:Although guideline-recommended intensive lipid-lowering therapy (LLT) reduces recurrent cardiovascular events after acute coronary syndrome (ACS), timely implementation of intensive LLT and achievement of low-density lipoprotein cholesterol (LDL-C) target remain suboptimal in routine clinical practice. OBJECTIVES:The purpose of this study was to determine whether a protocol-based implementation strategy improves timely achievement of guideline-recommended LDL-C target after ACS. METHODS:We conducted a cluster-randomized trial involving patients with ACS. Ten centers were randomly assigned 1:1 to protocol-based or standard lipid management. In the protocol-based group, LLT was initiated or intensified during the index hospitalization according to a prespecified algorithm based on baseline LLT status and LDL-C levels using high-intensity statins, ezetimibe, and PCSK9 inhibitors. LDL-C was reassessed at 4 weeks, with treatment escalation when indicated. In the protocol-based group, an LDL-C level of approximately 55 mg/dL was used as the protocol-specified operational threshold for intensification, whereas LDL-C <70 mg/dL was the treatment goal in both groups. The primary and key secondary endpoints were achievement of LDL-C <70 mg/dL and <55 mg/dL at 6 months, respectively. RESULTS:Between November 2024 and July 2025, 330 patients were enrolled, and 329 patients comprised the study population after 1 patient withdrew consent. The primary efficacy analysis included 315 patients with complete 6-month LDL-C data. Baseline characteristics were balanced between groups. The mean age was 69 years, 18% were women, and the median LDL-C level was 110 mg/dL. At 6 months, LDL-C <70 mg/dL was achieved in 86.4% vs 73.7% (between-group difference, 12.6 percentage points [95% CI: 3.8-21.5 percentage points]; P = 0.005); the corresponding difference was 12.8 percentage points (95% CI: -2.0 to 27.6 percentage points; P = 0.08) in a hospital-level sensitivity analysis. Similar findings were observed for LDL-C <55 mg/dL (60.8% vs 34.5%; between-group difference, 26.3 percentage points [95% CI: 18.5-34.0 percentage points]; P < 0.001). At 6 months, use of high-intensity statins, ezetimibe, and PCSK9 inhibitors was higher in the protocol-based group. CONCLUSIONS:A protocol-based implementation strategy for early intensive LLT significantly improved achievement of the guideline-recommended LDL-C target after ACS. These findings support a structured, algorithm-based care pathway to facilitate timely initiation and intensification of LLT and improve implementation of guideline-recommended lipid management in routine clinical practice. (Brief and Protocol-Based Intensive Lipid Management in Patients with Acute Coronary Syndrome; jRCT1020240029).
