Development of Novel Artificial Intelligence to Detect the Presence of Clinically Meaningful Coronary Atherosclerotic Stenosis in Major Branch from Coronary Angiography Video

Aim: The clinically meaningful coronary stenosis is diagnosed by trained interventional cardiologists. Whether artificial intelligence (AI) could detect coronary stenosis from CAG video is unclear. Methods: The 199 consecutive patients who underwent coronary arteriography (CAG) with chest pain between December 2018 and May 2019 was enrolled. Each patient underwent CAG with multiple view resulting in total numbers of 1,838 videos. A multi-layer 3-dimensional convolution neural network (CNN) was trained as an AI to detect clinically meaningful coronary artery stenosis diagnosed by the expert interventional cardiologist, using data from 146 patients (resulted in 1,359 videos) randomly selected from the entire dataset (training dataset). This training dataset was further split into 109 patients (989 videos) for derivation and 37 patients (370 videos) for validation. The AI developed in derivation cohort was tuned in validation cohort to make final model. Results: The final model was selected as the model with best performance in validation dataset. Then, the predictive accuracy of final model was tested with the remaining 53 patients (479 videos) in test dataset. Our AI model showed a c-statistic of 0.61 in validation dataset and 0.61 in test dataset, respectively. Conclusion: An artificial intelligence applied to CAG videos could detect clinically meaningful coronary atherosclerotic stenosis diagnosed by expert cardiologists with modest predictive value. Further studies with improved AI at larger sample size is necessary.     

Prediction of the no-reflow phenomenon during percutaneous coronary intervention using coronary computed tomography angiography

Coronary computed tomography angiography (CTA) can assess plaque characteristics and plaque size noninvasively. The purpose of this study was to investigate whether coronary CTA before percutaneous coronary intervention (PCI) can predict the no-reflow phenomenon during PCI. Seventy-eight patients [acute coronary syndrome (ACS) = 43, stable angina pectoris (SAP) = 35, male/female = 72/6, age: 65 ± 10 years] who underwent 16- or 64-slice CTA in the 4 weeks before PCI were enrolled. The low attenuation plaque size on CTA was compared between patients with (NR+) and without the no-reflow phenomenon (NR−). No-reflow phenomenon was observed in 11 patients, including 10 patients with ACS and 1 patient with SAP. Low attenuation plaque was detected in 9 (82%) NR(+) lesions and 35 (52%) NR(−) lesions. The length of low attenuation plaque was significantly longer in NR(+) than in NR(−) patients (9.0 ± 6.5 vs. 1.6 ± 2.7 mm, p < 0.0001). On step-wise regression analysis, ACS (p = 0.036, 95% CI = 0.009–0.258) and the presence of low attenuation plaque with a length >4.7 mm (p < 0.001, 95% CI = 0.447–0.778) were significant independent predictors of NR(−) no-reflow phenomenon. Low attenuation plaque with lesion length of >4.7 mm on coronary CTA and ACS were the significant predictors for the no-reflow phenomenon during PCI. Coronary CTA assessment before PCI would be useful to predict coronary events during PCI in advance.     

Endoscopically treated Cronkhite-Canada syndrome associated with minute intramucosal gastric cancer: an analysis of molecular pathology

There have been no reports of Cronkhite-Canada syndrome (CCS) associated gastric cancer resected with endoscopy because it is very difficult to identify small cancers that are candidates for endoscopic resection. We report a case of CCS with gastric cancer treated with endoscopic submucosal dissection, and we evaluate the molecular pathological analysis of malignant transformation in patients with CCS. A 74-year-old man had an advanced rectal cancer and gastrointestinal polyposis after presenting with hypoproteinemia, partial hair loss and atrophic nails as well as hyperpigmentation on the hands. He was diagnosed as having CCS. On upper endoscopy, a 7 mm discolored polyp with an irregular microvascular pattern revealed by magnified narrow-band imaging (NBI) was identified in gastric diffuse CCS polyposis. This lesion was treated with endoscopic submucosal dissection and diagnosed as a flat, elevated-type, mucosal well-differentiated tubular adenocarcinoma without lymphatic or venous infiltration, and with tumor-free margins. Microsatellite instability was detected in both the cancer and the surrounding CCS polyps. Mucin-histochemical analysis of the cancer area showed the complete intestinal type, and thus may have differentiated the CCS polyps from that of the common gastric hyperplastic polyps. This case illustrates that a clue to detecting small cancers may be to look for the discolored lesion among reddish CCS polyposis and thereafter to observe the irregular vascular pattern with NBI endoscopy. From the viewpoint of genetic alterations, patients with CCS polyps are considered to be at high risk for developing gastric cancer, and therefore careful follow-up examinations are necessary for the early detection of malignancies.     

IL-6 blockade preferentially inhibits Th17 differentiation in collagen-induced arthritis

We examined the time course of cytokine production by CD4 T cells from mice with collagen-induced arthritis (CIA), and we determined the influence of interleukin-6 (IL-6) blockade on cytokine production. CD4 T cells purified from spleen were cultured with both collagen and anti-CD28 antibody for 48 h and the production of interferon-γ (IFN-γ), IL-4, and IL-17 by the cells, secreted into the supernatants, was measured at various time intervals. The production of all these cytokines started 7 days after the first immunization. A marked increase in IFN-γ production was observed after the second immunization, but IL-4 and IL-17 production was not affected by a second immunization. A single injection of anti-mouse IL-6 receptor antibody (MR16-1) on the day of the first immunization suppressed the onset of arthritis. IL-17 production by CD4 T cells from MR16-1-treated mice was significantly lower than that from the control mice. On the other hand, treatment with MR16-1 showed only a tendency to suppress the production of IL-4 and IFN-γ. Injection of MR16-1 on day 21 did not suppress the onset of arthritis. We examined the direct influence of MR16-1 on cytokine production by differentiated CD4 T cells from arthritic mice. Production of IL-4, IFN-γ, and IL-17 was not affected by MR16-1. In conclusion, IL-6 inhibition preferentially suppresses the induction of Th17 cells and does not seem to impact on cytokine production of already differentiated Th17 cells.     

Copper incorporation into ceruloplasmin is regulated by Niemann–Pick C1 protein

Aim: Wilson disease is a genetic disorder of copper metabolism characterized by impaired biliary copper excretion. Wilson disease gene product (ATP7B) functions in copper incorporation to ceruloplasmin (Cp) and biliary copper excretion. Our previous study showed the late endosome localization of ATP7B and described the copper transport pathway from the late endosome to trans‐Golgi network (TGN). However, the cellular localization of ATP7B and copper metabolism in hepatocytes remains controversial. The present study was performed to evaluate the role of Niemann–Pick type C (NPC) gene product NPC1 on intracellular copper transport in hepatocytes. Methods: We induced the NPC phenotype using U18666A to modulate the vesicle traffic from the late endosome to TGN. Then, we examined the effect of NPC1 overexpression on the localization of ATP7B and secretion of holo‐Cp, a copper‐binding mature form of Cp. Results: Overexpression of NPC1 increased holo‐Cp secretion to culture medium of U18666A‐treated cells, but did not affect the secretion of albumin. Manipulation of NPC1 function affected the localization of ATP7B and late endosome markers, but did not change the localization of a TGN marker. ATP7B co‐localized with the late endosome markers, but not with the TGN marker. Conclusion: These findings suggest that ATP7B localizes in the late endosomes and that copper in the late endosomes is transported to the secretory compartment via an NPC1‐dependent pathway and incorporated into Cp.     

Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan

AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finall...     

Kurtosis and skewness of density histograms on inspiratory and expiratory CT scans in smokers

The aim of this study is to evaluate the relationship between lung function and kurtosis or skewness of lung density histograms on computed tomography (CT) in smokers. Forty-six smokers (age range 46?81 years), enrolled in the Lung Tissue Research Consortium, underwent pulmonary function tests (PFT) and chest CT at full inspiration and full expiration. On both inspiratory and expiratory scans, kurtosis and skewness of the density histograms were automatically measured by open-source software. Correlations between CT measurements and lung function were evaluated by the linear regression analysis. Although no significant correlations were found between inspiratory kurtosis or skewness and PFT results, expiratory kurtosis significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%predicted, R = -0.581, p < 0.001; FEV(1)/FVC, R = -0.612, p < 0.001; RV/TLC, R = 0.613, p < 0.001, respectively). Similarly, expiratory skewness showed significant correlations with PFT results (FEV(1)%predicted, R = -0.584, p < 0.001; FEV(1)/FVC, R = -0.619, p < 0.001; RV/TLC, R = 0.585, p < 0.001, respectively). Also, the expiratory/inspiratory (E/I) ratios of kurtosis and skewness significantly correlated with FEV(1)%predicted (p < 0.001), FEV(1)/FVC (p < 0.001), RV/TLC (p < 0.001), and the percentage of predicted value of diffusing capacity for carbon monoxide (kurtosis E/I ratio, p = 0.001; skewness E/I ratio, p = 0.03, respectively). We conclude therefore that expiratory values and the E/I ratios of kurtosis and skewness of CT densitometry reflect airflow limitation and air-trapping. Higher kurtosis or skewness on expiratory CT scan indicates more severe conditions in smokers.