Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.

Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

BACKGROUND: The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production. METHOD: Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aß production in COS cells transfected with wild-type or mutant PSEN1. RESULTS: The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aß42 in PSEN1 G266S-transfected cells significantly increased. CONCLUSION: Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

Validation of the area under the Watts factor curve during the voiding cycle as a novel parameter for diagnosing detrusor underactivity in females.

OBJECTIVE: Detrusor underactivity (DU) is a common cause of lower urinary tract symptoms (LUTS). To date, no consensus has been reached on the urodynamic criteria for defining DU. We previously proposed the area under the curve of the Watts factor (WF-AUC) as a new parameter for diagnosing DU. By comparing previously reported five criteria for DU and WF-AUC, we analyzed whether the WF-AUC could assess detrusor contraction in women with LUTS. METHODS: Using urodynamic data of consecutive 77 women with LUTS, first, we classified DU based on previously reported five criteria. Second, we assessed the potential correlation between multiple parameters and WF-AUC. Third, receiver operating characteristic curve analysis was performed to determine the cutoff value of WF-AUC for diagnosing DU based on previously reported five criteria. Fourth, a linear regression analysis was conducted and compared using multiple criteria and female bladder outlet obstruction index (BOOIf). RESULTS: WF-AUC was positively correlated with the maximum values of WF, bladder contractility index (BCI), and projected isovolumetric pressure 1 (PIP1) with correlation coefficients of 0.63, 0.57, and 0.34, respectively. AUC for diagnosing DU based on previously reported five criteria ranging from 0.773 to 0.896 with different cutoff values of AUC-WF. The Spearman's correlation test revealed that BOOIf was significantly correlated with BCI, but not Wmax, PIP1 and WF-AUC. CONCLUSIONS: This study demonstrated the non-inferiority of the WF-AUC compared to previously reported criteria for defining DU. Depending on the cutoff value, the WF-AUC could appropriately evaluate women with DU, regardless of the presence of BOO.

Hyalinizing Clear Cell Carcinoma in the Sphenoid Sinus.

ABSTRACT: A 39-year-old man presented with a 1-month history of headaches. Imaging revealed a mass with extensive destruction. T2-weighted imaging displayed mixture of low and sponge-like high intensities and also dark area, with FDG PET/CT showing uneven but intense accumulation. Biopsy confirmed EWSR1 rearrangement, and hyalinizing clear cell carcinoma (HCCC) was diagnosed. HCCC, recently renamed from clear cell carcinoma in the fifth edition of the World Health Organization Classification of Head and Neck Tumors, is a rare tumor. This case describes the features of T2-weighted imaging and FDG PET patterns in HCCC, possibly contributing to their consideration in the differential diagnosis.

LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Ameliorates Endothelial Dysfunction in Diabetic C57BL/6 Mice.

AIMS: LCZ696 (sacubitril/valsartan) exerts cardioprotective effects. Recent studies have suggested that it improves the endothelial function; however, the underlying mechanisms have not been thoroughly investigated. We investigated whether LCZ696 ameliorates diabetes-induced endothelial dysfunction. METHODS: Diabetes was induced using streptozotocin in 8-week-old male C57BL/6 mice. Diabetic mice were randomly assigned to receive LCZ696 (100 mg/kg/day), valsartan (50 mg/kg/day), or a vehicle for three weeks. The endothelium-dependent and endothelium-independent vascular responses of the aortic segments were determined based on the response to acetylcholine and sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVEC) and aortic segments obtained from C57BL/6 mice were used to perform in vitro and ex vivo experiments, respectively. RESULTS: LCZ696 and valsartan reduced the blood pressure in diabetic mice (P＜0.05). The administration of LCZ696 (P＜0.001) and valsartan (P＜0.01) ameliorated endothelium-dependent vascular relaxation, but not endothelium-independent vascular relaxation, under diabetic conditions. LCZ696, but not valsartan, increased eNOSSer1177 (P=0.06) and Akt (P＜0.05) phosphorylation in the aorta. In HUVEC, methylglyoxal (MGO), a major precursor of advanced glycation end products, decreased eNOSSer1177 phosphorylation (P＜0.05) and increased eNOSThr495 phosphorylation (P＜0.001). However, atrial natriuretic peptide (ANP) reversed these effects. ANP also ameliorated the MGO-induced impairment of endothelium-dependent vascular relaxation in the aortic segments (P＜0.05), although L-NAME completely blocked this effect (P＜0.001). CONCLUSION: LCZ696 ameliorated diabetes-induced endothelial dysfunction by increasing the bioavailability of ANP. Our findings suggest that LCZ696 has a vascular protective effect in a diabetic model and highlight that it may be more effective than valsartan.

Quantitative MRI Biomarkers Measure Changes in Targeted Brain Areas in Patients With Obesity.

CONTEXT: Obesity is accompanied by damages to several tissues, including the brain. Pathological data and animal models have demonstrated an increased inflammatory reaction in hypothalamus and hippocampus. OBJECTIVE: We tested whether we could observe such pathological modifications in vivo through quantitative magnetic resonance imaging (MRI) metrics. METHODS: This prospective study was conducted between May 2019 and November 2022. The study was conducted in the Specialized Center for the Care of Obesity in a French University Hospital. Twenty-seven patients with obesity and 23 age and gender-paired normal-weight controls were prospectively recruited. All participants were examined using brain MRI. Anthropometric and biological data, eating behavior, anxiety, depression, and memory performance were assessed in both groups. The main outcome measure was brain MRI with the following parametric maps: quantitative susceptibility mapping (QSM), mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio map, and T2 relaxivity map. RESULTS: In the hypothalamus, patients with obesity had higher FA and lower QSM than normal-weight controls. In the hippocampus, patients with obesity had higher FA and lower MD. There was no correlation between imaging biomarkers and eating behavior or anxiety. CONCLUSION: Our findings are consistent with the presence of neuroinflammation in brain regions involved in food intake. In vivo brain biomarkers from quantitative MRI appear to provide an incremental information for the assessment of brain damages in patients with obesity.

Vulnerability of Thalamic Nuclei at CSF Interface During the Entire Course of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Thalamic atrophy can be used as a proxy for neurodegeneration in multiple sclerosis (MS). Some data point toward thalamic nuclei that could be affected more than others. However, the dynamic of their changes during MS evolution and the mechanisms driving their differential alterations are still uncertain. METHODS: We paired a large cohort of 1,123 patients with MS with the same number of healthy controls, all scanned with conventional 3D-T1 MRI. To highlight the main atrophic regions at the thalamic nuclei level, we validated a segmentation strategy consisting of deep learning-based synthesis of sequences, which were used for automatic multiatlas segmentation. Then, through a lifespan-based approach, we could model the dynamics of the 4 main thalamic nuclei groups. RESULTS: All analyses converged toward a higher rate of atrophy for the posterior and medial groups compared with the anterior and lateral groups. We also demonstrated that focal MS white matter lesions were associated with atrophy of groups of nuclei when specifically located within the associated thalamocortical projections. The volumes of the most affected posterior group, but also of the anterior group, were better associated with clinical disability than the volume of the whole thalamus. DISCUSSION: These findings point toward the thalamic nuclei adjacent to the third ventricle as more susceptible to neurodegeneration during the entire course of MS through potentiation of disconnection effects by regional factors. Because this information can be obtained even from standard T1-weighted MRI, this paves the way toward such an approach for future monitoring of patients with MS.