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早期に治療介入できた免疫関連有害事象（irAE）による劇症1型糖尿病の1例
Get PDFThe patient, a woman in her 60s, was undergoing treatment with an anti-PD-1 antibody, an immune checkpoint inhibitor （ICI）, to address lung metastases following hard palate cancer resection. Four years after initiating treatment, during a visit to an otorhinolaryngologist, her HbA1c levels were found to be slightly elevated without any precipitating factors. Five days after referral to the endocrinology department, the patient exhibited hyperglycemic symptoms and ketosis. We ultimately diagnosed fulminant type 1 diabetes. Immune-related adverse events （irAEs） due to ICI usage manifest throughout the body, including the skin, lungs, and endocrine organs. Fulminant type 1 diabetes triggered by irAEs progresses with alarming rapidity and poses a significant mortality risk unless diagnosed and treated with insulin expeditiously. Although irAEs are closely monitored following ICI administration, patients are frequently misdiagnosed with incidental hyperglycemia and managed as type 2 diabetes. In this case, an irAE was detected due to a slight increase in HbA1c during a routine examination prompted the consideration of an irAE, leading to a swift referral to a specialist department. Consequently, treatment was initiated before symptoms became severe, allowing the early resumption of the appropriate therapy for the primary disease.journal articl
The association between alcohol consumption and cardiometabolic factors and liver fibrosis in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated liver disease
Get PDFBackground: The relationships between alcohol consumption, cardiometabolic factors, and liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease and those with metabolic dysfunction and alcohol-associated liver disease remain unclear.
Aims: To investigate the longitudinal associations among alcohol consumption, cardiometabolic factors, and liver fibrosis in patients with these two liver diseases.
Methods: This observational cohort study included 1866 patients with metabolic dysfunction-associated steatotic liver disease and 521 patients with metabolic dysfunction and alcohol-associated liver disease who underwent > two health checkups over >2 years. The associations of both liver diseases with worsening non-invasive liver fibrosis scores were assessed using the Cox regression analysis.
Results: Both liver diseases independently worsened liver fibrosis in both sexes. However, the hazard ratio for worsening liver fibrosis in females was significantly higher with metabolic dysfunction and alcohol-associated liver disease than with metabolic dysfunction-associated steatotic liver disease. Worsening liver fibrosis was not associated with alcohol consumption. Among males with metabolic dysfunction-associated steatotic liver disease, the hazard ratio for worsening liver fibrosis was significantly higher in those with multiple cardiometabolic factors compared to those with a single cardiometabolic factor.
Conclusions: Although both metabolic steatotic liver disease and metabolic alcohol-associated liver disease were correlated with liver fibrosis progression in both sexes, the impact of alcohol consumption and cardiometabolic factors on fibrosis progression differed by sex. Cardiometabolic factors may have a stronger impact on liver fibrosis than alcohol consumption in males with metabolic dysfunction-associated steatotic liver disease.journal articl
Index estimate by first Betti number of minimal hypersurface in compact symmetric space: Part I
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Porphyromonas gingivalis outer membrane vesicles increase vascular permeability by inducing stress fiber formation and degrading vascular endothelial-cadherin in endothelial cells
Get PDFPorphyromonas gingivalis (Pg) is a keystone bacterium associated with systemic diseases, such as diabetes mellitus and Alzheimer's disease. Outer membrane vesicles (OMVs) released from Pg have been implicated in systemic diseases by delivering Pg virulence factors to host cells in distant organs and inducing cellular dysfunction. Pg OMVs also have the potential to enter distant organs via the bloodstream. However, the effects of Pg OMVs on the vascular function are poorly understood. Here, we showed that Pg OMVs increase vascular permeability by promoting stress fiber formation and lysosome/endosome-mediated vascular endothelial-cadherin (VEc) degradation in human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs). F-actin, visualized via fluorescein isothiocyanate-phalloidin, became thicker and longer, leading to the formation of radical stress fibers in response to Pg OMVs in HUVECs and HPMECs. Western blotting and quantitative real-time polymerase chain reaction analyses revealed that Pg OMVs decreased VEc protein levels in a gene-independent manner. Pg OMVs enhanced vesicular VEc accumulation in the cytoplasm around lysosome-associated membrane protein 1-positive structures during pretreatment with the lysosomal inhibitor chloroquine. This suggests that Pg OMVs decrease VEc protein levels by accelerating their internalization and degradation via lysosomes and endosomes. A27632 inhibition of Rho kinases impaired the Pg OMV-induced stress fiber formation and VEc degradation, resulting in the recovery of hyperpermeability. These findings provide new insights into the pathogenesis of systemic diseases that are associated with periodontal diseases.journal articl
Spontaneous thrombosis of a giant aneurysm complicated with the coronary-to-pulmonary artery fistula : a case report
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A coronary-to-pulmonary artery fistula (CPAF) with a giant aneurysm is a rare clinical occurrence. The rupture of an aneurysm leads to a fatal outcome, thus prompting the incorporation of prophylactic measures, which have encompassed surgical resections or endovascular embolization procedures. The indications for these treatment strategies are controversial, and little has been elucidated regarding the salient characteristics underpinning the selection of a therapeutic strategy. We report a case of a giant aneurysm associated with CPAFs that was thrombosed before interventional treatment.
Case summary
A 43-year-old woman, who had previously undergone a right adrenalectomy for primary aldosteronism, was referred for an abnormal heart silhouette on a chest X-ray, which had not been seen three years earlier. Contrast-enhanced computed tomography and coronary angiography (CAG) revealed a giant aneurysm on the anterior aspect of the heart associated with two CPAFs. Because of the risk of rupture of the aneurysm, surgical resection was recommended; however, the patient requested endovascular therapy. On the day of intervention, CAG showed spontaneous occlusion of the feeding vessel to the aneurysm, and the aneurysm showed minimal contrast agent, suggesting spontaneous thrombosis. Because of possible recanalization of the aneurysm, coil embolization was performed, without complications. The patient remained asymptomatic, and the aneurysm was completely embolized at the one-year follow-up.
Discussion
The case shows that minimally invasive endovascular treatment is feasible instead of surgical resection for giant aneurysms associated with CPAFs, depending on their morphological characteristics. This perspective may offer novel insights into treatment strategies for CPAF.journal articl
All-trans retinoic acid induces lipophagy through the activation of the AMPK-Beclin1 signaling pathway and reduces Rubicon expression in adipocytes
Get PDFLipophagy is defined as a lipolysis pathway that degrades lipid droplet (LD) via autophagy. All-trans retinoic acid (atRA), a metabolite of vitamin A, stimulates lipolysis through hormone-sensitive lipase and β-oxidation. However, the regulation of lipolysis by atRA-induced autophagy in adipocytes remains unclear. In this study, we investigated the effect of atRA on autophagy in epididymal fat of mice and the molecular mechanisms of autophagy in 3T3-L1 adipocytes. Western blotting showed that atRA decreased the expression of p62, a cargo receptor for autophagic degradation, and increased the expression of the lipidated LC3B (LC3B-II), an autophagy marker, in epididymal fat. Next, we confirmed that atRA increased autophagic flux in differentiated 3T3-L1 cells using the GFP-LC3-RFP-LC3ΔG probe. Immunofluorescent staining revealed that the colocalization of LC3B with perilipin increased in differentiated 3T3-L1 cells treated with atRA. The knockdown of Atg5, an essential gene in autophagy induction, partly suppressed the atRA-induced release of non-esterified fatty acid (NEFA) from LDs in differentiated 3T3-L1 cells. atRA time-dependently elicited the phosphorylation of AMPK and Beclin1, autophagy-inducing factors, in mature 3T3-L1 adipocytes. Inversely, atRA decreased the protein expression of Rubicon, an autophagy repressor, in differentiated 3T3-L1 cells and epididymal fat. Interestingly, the expression of ALDH1A1, atRA-synthesizing enzymes, increased in epididymal fat with decreased protein expression of Rubicon in aged mice. These results suggest that atRA may partially induce lipolysis through lipophagy by activating the AMPK-Beclin1 signaling pathway in the adipocytes and increased atRA levels may contribute to decreased Rubicon expression in the epididymal fat of aged mice.doctoral thesi
Probing the Optoelectronic Behavior of 2D Nanomaterials Synthesized by Laser Ablation and Hydrothermal Method
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Impact of Olfactory Change on Postoperative Body Weight Loss in Patients with Gastric Cancer after Gastrectomy
Get PDFPatients undergoing gastrectomy for gastric cancer may experience alterations in olfaction, yet the association between olfactory changes and postoperative weight loss remains uncertain. This study aimed to elucidate the relationship between olfactory changes and postoperative weight loss in patients with gastric cancer. Patients who underwent radical gastrectomy for gastric cancer between February 2022 and August 2022 were included in the study. Those experiencing a higher Visual Analog Scale (VAS) score postoperatively compared to preoperatively were deemed to have undergone olfactory changes. Postoperative weight loss was determined using the 75th percentile as a cutoff value, designating patients surpassing this threshold as experiencing significant weight loss. Multivariate logistic regression analysis was employed to identify risk factors for postoperative weight loss, with statistical significance set at p < 0.05. Out of 58 patients, 10 (17.2%) exhibited olfactory changes. The rate of postoperative weight loss at one month was markedly higher in the group with olfactory changes compared to those without (9.6% versus 6.2%, respectively; p = 0.002). In addition, the group experiencing olfactory changes demonstrated significantly lower energy intake compared to the group without such changes (1050 kcal versus 1250 kcal, respectively; p = 0.029). Logistic regression analysis revealed olfactory changes as an independent risk factor for significant weight loss at one month postoperatively (odds ratio: 7.64, 95% confidence interval: 1.09–71.85, p = 0.048). In conclusion, olfactory changes emerged as an independent risk factor for postoperative weight loss at one month in patients with gastric cancer following gastrectomy.doctoral thesi
Changes in higher-level functional capacity during the COVID-19 pandemic among older adults living in Japan
Get PDFObjective : To evaluate change in higher-level functional capacity of older Japanese individuals during the COVID-19 pandemic. Methods : Four hundred older Japanese individuals completed an online questionnaire in early May 2021. Participants were asked retrospectively about their higher-level functional capacity and lifestyle before and during the COVID-19 pandemic. Higher-level functional capacity was determined as total score on the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). Total TMIG-IC score ranges from 0 to 13. A decline in higher-level functional capacity was defined as a decrease in TMIG-IC score of more than 2 points during the COVID-19 pandemic. Changes in higher-level functional capacity during the COVID-19 pandemic were assessed by paired t-test and a general linear model. Results : Decreased TMIG-IC scores were found in 43 (21.5%) men and 61 (30.5%) women. Among those with higher-level functional capacity, scores for total TMIG-IC and Social Role decreased significantly in both sexes (all p< 0.005). Conclusion : The findings suggest an association of the COVID-19 pandemic with a decrease in higher-level functional capacity, especially in Social Role, among older adults living in Japan.journal articl