Bleeding risk factors and real-world antithrombotic therapies in elderly patients with atrial fibrillation undergoing percutaneous coronary intervention: a retrospective study.

BACKGROUND: Bleeding risk factors in elderly patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) are unclear and data on the use of antithrombotic drugs are lacking. We investigated the bleeding risk factors in elderly patients with atrial fibrillation undergoing PCI to help optimize antithrombotic therapy according to bleeding risk. We also investigated the association between the actual use of antithrombotic therapy and bleeding events. METHODS: A retrospective cohort study was conducted on 134 elderly patients with atrial fibrillation who underwent primary PCI at the Department of Cardiology, Showa University Fujigaoka Hospital. The endpoint was a bleeding event within 1-year. Bleeding risk factors were identified using multivariate analysis. The association between the number of antithrombotics and bleeding events was evaluated using the chi-squared test. RESULTS: The mean age of the patients was 76.0 ± 6.2 years. Bleeding events occurred in 41 (30.6%) patients. Age > 80 years (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.10-5.85), multivessel disease (OR: 2.76, 95% CI: 1.22-6.23), and history of surgery (OR: 3.03, 95% CI: 1.14-8.06) were identified as bleeding risk factors. The proportion of patients receiving triple therapy was significantly higher in the bleeding group compared to the non-bleeding group (70.7% vs. 27.5%, p < 0.001). CONCLUSIONS: Age > 80, multivessel disease, and history of surgery were found to be risk factors for bleeding in elderly patients with atrial fibrillation undergoing PCI. In addition, dual therapy after PCI in elderly patients at high risk of bleeding should be considered to avoid bleeding events.

Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa.

Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further.

Development of a model predicting cardiac events in heart failure patients with decreased renal function: a retrospective study.

BACKGROUND: Inappropriate and multiple medications affect the prognosis of patients with acute decompensated heart failure (ADHF). However, in ADHF patients with decreased renal function, there have been no reports on prognostic factors, including medication data, or models for predicting cardiac events. AIM: To develop a model including medication data to predict cardiac events in ADHF patients with decreased renal function. METHOD: This retrospective cohort study included 443 first-time admitted ADHF patients with decreased renal function (estimated glomerular filtration rate < 60 mL/min/1.73 m2 at discharge) in the Showa University Fujigaoka Hospital. The primary outcome was cardiac events within one year after discharge, defined as the composite of HF readmission, HF mortality, and cardiovascular mortality. The model for predicting cardiac events was developed using predictive factors extracted by multivariable analysis. The cardiac events curves were visualized using the Kaplan-Meier method and estimated using a log-rank test. RESULTS: The incidence of cardiac events within one year after discharge was 20.1%. By multivariable analysis, we observed that atrial fibrillation, weight loss < 5%, brain natriuretic peptide ≥ 200 pg/mL, polypharmacy, and beta-blockers use below target dosage were significantly associated with an increased risk of cardiac events. The developed model, the cardiac events rate in the high-risk group was significantly higher than in the low-risk group (41.0 vs. 9.2%, p < 0.001). CONCLUSION: The developed model for predicting cardiac events will be useful in decision-making to support appropriate early management of ADHF patients with decreased renal function.

[Long-Term Survival from Gastric Cancer Treated with Radiotherapy for Distant Lymph Node Recurrence-A Case Report].

A 69-year-old man was diagnosed with advanced gastric cancer in the upper body of the stomach and underwent total gastrectomy with D2 lymph node dissection. At the diagnosis, the pathological stage was T2N3M0(Stage ⅢA). The patient underwent adjuvant chemotherapy with S-1 for a year. Two years after surgery, metastasis in subclavian and axillary lymph nodes was diagnosed by positron emission tomography-computed tomography(PET-CT). He rejected systemic chemotherapy, and radiotherapy(RT)at 56 Gy/28 Fr was administered. After RT, the metastatic lymph node completely regressed. However, CT showed lymph node metastasis in the right cervical, supraclavicular, and mediastinal zones over 1 year and 6 months after RT. These body regions received RT at a total dose of 40 Gy/20 Fr, and cancer significantly shrank again. Five years after following the second RT, the patient remains alive with no signs of relapse. RT may be a promising method for localized distant metastasis in patients who did not receive chemotherapy.

Strangulation of the small intestine caused by an intra-mesosigmoid hernia: a case report.

Sigmoid mesocolon hernia is an uncommon type of internal hernia with only a few cases reported to date. This disease entity can progress rapidly to cause vascular disturbance, necrosis, and perforation of the bowel wall; therefore, early diagnosis and surgical treatment are essential. We describe the case of an intra-mesosigmoid hernia in a 60-year-old man without history of previous abdominal surgery who presented with sudden acute abdominal pain and vomiting. Based on computed tomography, which showed ascites and small bowel obstruction, we diagnosed him as having strangulation of the small intestine caused by a sigmoid mesocolic hernia and performed emergency surgery. Laparotomy revealed small intestinal strangulation, extensive engorgement, and discoloration of bowel loops. Approximately 100 cm of the small intestine extending from the ligament of Treitz had undergone strangulation and herniated into the defect of sigmoid mesocolon, leading to a diagnosis of an intra-mesosigmoid hernia. Because the incarcerated portion of the small intestine was viable, we did not perform intestinal resection and reconstruction but closed the defect in the sigmoid mesocolon. His postoperative course was uneventful.

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

Facilitation of endoglin-targeting cancer therapy by development/utilization of a novel genetically engineered mouse model expressing humanized endoglin (CD105).

Endoglin (ENG) is a TGF-ß coreceptor and essential for vascular development and angiogenesis. A chimeric antihuman ENG (hENG) monoclonal antibody (mAb) c-SN6j (also known as TRC105) shows promising safety and clinical efficacy features in multiple clinical trials of patients with various advanced solid tumors. Here we developed a novel genetically engineered mouse model to optimize the ENG-targeting clinical trials. We designed a new targeting vector that contains exons 4-8 of hENG gene to generate novel genetically engineered mice (GEMs) expressing functional human/mouse chimeric (humanized) ENG with desired epitopes. Genotyping of the generated mice confirmed that we generated the desired GEMs. Immunohistochemical analysis demonstrated that humanized ENG protein of the GEMs expresses epitopes defined by 7 of our 8 anti-hENG mAbs tested. Surprisingly the homozygous GEMs develop normally and are healthy. Established breast and colon tumors as well as metastasis and tumor microvessels in the GEMs were effectively suppressed by systemic administration of anti-hENG mAbs. Additionally, test result indicates that synergistic potentiation of antitumor efficacy can be induced by simultaneous targeting of two distinct epitopes by anti-hENG mAbs. Sorafenib and capecitabine also showed antitumor efficacy in the GEMs. The presented novel GEMs are the first GEMs that express the targetable humanized ENG. Test results indicate utility of the GEMs for the clinically relevant studies. Additionally, we generated GEMs expressing a different humanized ENG containing exons 5-6 of hENG gene, and the homozygous GEMs develop normally and are healthy.

[Social concern and independence in adults with congenital heart disease].

OBJECTIVES: Recent advances in medical and surgical treatment have led to the survival of increasing numbers of adults with congenital heart disease (CHD). However, the social status of these patients remains unknown. This survey investigated the social prospects for adults with CHD, and the limiting factors for social independence. METHODS: A written questionnaire on patient characteristics, education, employability, marital status and insurability was designed to define the characteristics of social independence in adults with CHD. Randomly selected adults with CHD were enrolled: 13 patients with cyanotic unrepaired CHD (4 males, 9 females, mean age: 29.8 +/- 10 years, range: 18-56 years) and 102 patients with other CHDs (48 males, 54 females, mean age: 29.5 +/- 10 years, range: 18-74 years). RESULTS: University of California at Los Angeles functional class I-II was found in 94% of patients, medication in 46%, and hospitalization in 51%. Compared with the data from Japanese general population, study patients had a lower ratio of high school graduates (86% vs 94%), life insurability (51% vs 71%), marital status (31% vs 32%) and employability (82% vs 80%). Patients with unrepaired cyanotic CHD had significantly lower ratio than those with other CHDs (marital status 15%, p = 0.19; employability 40%, p = 0.0003; high school graduates 69%, p = 0.06; life insurability 18%, p = 0.02, respectively). CONCLUSIONS: Factors affecting social independence in adults with CHD were severity of disease, continuing medication, lower level of education, lower self-esteem, and unknown natural history of CHD. To improve social independence in these patients, further development of medical and surgical therapy and more detailed knowledge of the patients, caretakers and society in this field are needed.