Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan

BACKGROUND: Data on the risk of cardiovascular-related mortality in patients with cancer are limited. METHODS AND RESULTS: This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. CONCLUSIONS: Cancer survivors have a higher risk of fatal heart disease than the general population.Gon Y., Zha L., Sasaki T., et al. Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan. Journal of the American Heart Association 12, e029967 (2023); https://doi.org/10.1161/JAHA.123.029967

Expression of alpha smooth muscle actin in living donor liver transplant recipients

Recently, there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression. Herein, we focused on activated hepatic stellate cells expressing alpha smooth muscle actin (α-SMA) to understand the correlation between immunosuppressant medication and liver fibrosis. The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy. The number of α-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy. In addition, the α-SMA-positive area evaluated using the Win- RooF image processing software program continued to increase over time in three adult transplanted patients with liver fibrosis, and the α-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases, according to a retrospective review. Therefore, α-SMA could be a useful marker for the detection of early stage fibrosis

Usefulness of fluorine-18 fluorodeoxyglucose-positron emission tomography in management strategy for thymic epithelial tumors

Background: This study investigated the usefulness of fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) during the treatment of thymic epithelial tumors in combination with Ki-67 evaluation based on surgical cases in our department. Methods: Between November 2003 and May 2011, 39 patients with thymic epithelial tumor underwent preoperative FDG-PET. The maximum standardized uptake value (SUVmax) of each category within Masaoka stage, World Health Organization classification, tumor diameter, myasthenia gravis, and Ki-67 label index were compared. To examine risk factors for relapse, SUVmax, age, sex, and surgical radicality were investigated in addition to those items. Results: The mean SUVmax was 4.5 (range, 1.2 to 14.6) and was significantly higher for Masaoka stage IV than for I and II (all p < 0.008) and for World Health Organization classified thymic cancer compared with all other types (all p < 0.0001). Mean SUVmax revealed significantly higher values for large tumors than for small tumors (p = 0.02). Mean SUVmax was significantly higher for high Ki-67-positive samples (p = 0.0004), indicating a strong correlation between SUVmax and the Ki-67 label index (ρ = 0.77, p = 0.0001). SUVmax accurately reflected therapeutic efficacy in patients with induction therapy. Univariate analysis revealed Masaoka stages III and IV and pathologically incomplete resection as risk factors for relapse. On multivariate analysis, independent risk factors for relapse comprised only Masaoka stages III and IV. Conclusions: FDG-PET SUVmax does reflect proliferation and invasiveness of thymic epithelial tumors and can provide an index for diagnosis and treatment, although it is not a risk factor for relapse. FDG-PET is also useful for evaluating induction therapy efficacy and detecting relapse. © 2013 The Society of Thoracic Surgeons

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren\u27s Syndrome

Although it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren\u27s syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs). T-iPS-DCs had dendritic cell-like morphology, and expressed CD11c, HLA-DR, CD80, CD86, and also BDCA-3. Compared with monocyte-derived DCs, the capacity for antigen processing was similar, and T-iPS-DCs induced the proliferative response of autoreactive CD4+ T cells. Moreover, we could evaluate T cell functions of the patient with SS. In conclusion, we obtained adequate numbers of DCs from T-iPSCs, which could be used to characterize pathogenic T cells in autoimmune diseases such as SS