Colon perforation with fecal peritonitis is usually fatal without prompt surgical intervention. We report the case of an 89-year-old woman with colon perforation and extraluminal feces who survived for 174 days without surgery in the presence of extensive postoperative peritoneal adhesions. The patient had previously undergone two abdominal surgeries for colorectal cancer, resulting in severe intra-abdominal adhesions. Despite radiological evidence of intraperitoneal free air and extraluminal feces, she was managed conservatively with antibiotics, morphine hydrochloride, supportive care, and close monitoring. This case suggests that, in carefully selected patients with marked peritoneal adhesions, non-operative management may warrant reconsideration as a potential therapeutic option for colon perforation before deeming that the condition is inoperable.
PURPOSE:Although neuropathological comorbidities, including Alzheimer's disease neuropathological change (AD-NC) and limbic-predominant age-related TAR DNA-binding protein 43encephalopathy neuropathological change (LATE-NC), are associated with medial temporal atrophy in patients with Lewy body disease (LBD), the diagnostic performance of magnetic resonance imaging (MRI)-derived indices remains unclear. This study aimed to investigate the diagnostic performance of MRI-derived indices representing medial temporal atrophy in differentiating between LBD with AD-NC and/or LATE-NC (mixed LBD [mLBD]) and without these comorbidities (pure LBD [pLBD]). METHODS:This study included 24 and 16 patients with pathologically confirmed mLBD and pLBD, respectively. In addition to the well-known medial temporal atrophy and entorhinal cortex atrophy (ERICA) scores, the cross-sectional areas of the bilateral entorhinal cortices/parahippocampal gyri (ABEP) were segmented manually. RESULTS:Even incorporating various covariates such as age at MRI examination, sex, argyrophilic grain, the MRI-derived indices, especially ABEP, significantly correlated with the severity of AD-NC, and showed a trend of correlation with LATE-NC. For the differentiation between all mLBD and pLBD, the ERICA score and ABEP demonstrated higher diagnostic performance (area under the receiver-operating-characteristic curve [AUC] of 0.80 and 0.87, respectively). Additionally, the highest diagnostic performance for ABEP (AUC, 0.94; sensitivity, 100%; specificity, 88.9%; accuracy, 96%) was observed in differentiating between pLBD and mLBD with two comorbidities (AD-NC and LATE-NC). CONCLUSION:In patients with pathologically confirmed LBD, medial temporal atrophy was significantly correlated with AD-NC, and showed a trend of correlation with LATE-NC. Moreover, MRI-derived indices indicative of medial temporal atrophy were useful in diagnosing these comorbidities.
The causes of Alzheimer's disease (AD) are poorly understood, although many genes are known to be involved in this pathology. To gain insights into the underlying molecular mechanisms, it is essential to identify the relationships between individual AD genes. Previous work has shown that the splice variant E of KLC1 (KLC1_vE) promotes AD, and that the CELF1 gene, which encodes an RNA-binding protein involved in splicing regulation, is at a risk locus for AD. Here, we identified a functional link between CELF1 and KLC1 in AD pathogenesis. Transcriptomic data from human samples from different ethnic groups revealed that CELF1 mRNA levels are low in AD brains, and the splicing pattern of KLC1 is strongly correlated with CELF1 expression levels. Specifically, KLC1_vE is negatively correlated with CELF1. Depletion and overexpression experiments in cultured cells demonstrated that the CELF1 protein down-regulates KLC1_vE. In a cross-linking and immunoprecipitation sequencing (CLIP-seq) database, CELF1 directly binds to KLC1 RNA, following which it likely modulates terminal exon usage, hence KLC1_vE formation. These findings reveal a new pathogenic pathway where a risk allele of CELF1 is associated with reduced CELF1 expression, which up-regulates KLC1_vE to promote AD.
