Case report: Stereotactic body radiation therapy with 12 Gy for silencing refractory ventricular tachycardia.

Background: Encouraging results have been reported for the treatment of ventricular tachycardia (VT) with stereotactic body radiation therapy (SBRT) with 25 Gy. SBRT with 12 Gy for refractory VT was designed to reduce long-term cardiac toxicity. Methods: Stereotactic body radiation therapy-VT simulation, planning, and treatment were performed using standard techniques. A patient was treated with a marginal dose of 12 Gy in a single fraction to the planning target volume (PTV). The goal was for at least ≥ 95% of the PTV to be covered by at least 95% of 12 Gy radiation. Results: From April 2021 through June 2022, a patient with refractory VT underwent treatment. The volume for PTV was 65.8 cm3. The mean radiation dose administered to the heart (the heart volume excluding the PTV) was 2.2 Gy. No acute or late toxicity was observed after SBRT. Six months after SBRT, the patient experienced new monomorphic right ventricular outflow tract (RVOT) VT. Interestingly, the substrate of the left ventricular basal to middle posteroseptal wall before SBRT was turned into scar zones with a local voltage < 0.5 mV. Catheter ablation to treat RVOT VT was performed, and the situation remains stable to date. Conclusion: This study reports the first patient with refractory VT successfully treated with 12.0 Gy SBRT, suggesting that 12 Gy is a potential dose to treat refractory VT. Further investigations and enrollment of more patients are warranted to assess the long-term efficacy and side effects of this treatment.

Extracellular matrix protein laminin enhances mesenchymal stem cell (MSC) paracrine function through αvß3/CD61 integrin to reduce cardiomyocyte apoptosis.

Myocardial ischaemia (MI) results in extensive cardiomyocyte death and reactive oxygen species (ROS)-induced damage in an organ with little or no regenerative capacity. Although the use of adult bone marrow mesenchymal stem cells (BMMSCs) has been proposed as a treatment option, the high cell numbers required for clinical use are difficult to achieve with this source of MSCs, and animal studies have produced inconsistent data. We recently demonstrated in small and large animal models of acute MI that the application of human term placenta-derived multipotent cells (PDMCs), a foetal-stage MSC, resulted in reversal of cardiac injury with therapeutic efficacy. However, the mechanisms involved are unclear, making it difficult to strategize for therapeutic improvements. We found that PDMCs significantly reduced cardiomyocyte apoptosis and ROS production through the paracrine factors GRO-α, HGF and IL-8. Moreover, culturing PDMCs on plates coated with laminin, an extracellular matrix (ECM) protein, resulted in significantly enhanced secretion of all three paracrine factors, which further reduced cardiomyocyte apoptosis. The enhancement of PDMC paracrine function by laminin was mediated through αvß3 integrin, with involvement of the signalling pathways of JNK, for GRO-α and IL-8 secretion, and PI3K/AKT, for HGF secretion. Our results demonstrated the utility of PDMC therapy to reduce cardiomyocyte apoptosis through modulation of ECM proteins in in vitro culture systems as a strategy to enhance the therapeutic functions of stem cells.

Epidemiology and socioeconomic features of appendicitis in Taiwan: a 12-year population-based study.

INTRODUCTION: This paper presents an epidemiologic study of appendicitis in Taiwan over a twelve-year period. An analysis of the incidence in the low-income population (LIP) is included to explore the effects of lower socioeconomic status on appendicitis. METHODS: We analyzed the epidemiological features of appendicitis in Taiwan using data from the National Health Insurance Research Database (NHIRD) from 2000 to 2011. All cases diagnosed as appendicitis were enrolled. RESULTS: The overall incidences of appendicitis, primary appendectomy, and perforated appendicitis were 107.76, 101.58, and 27.20 per 100,000 per year, respectively. The highest incidence of appendicitis was found in persons aged 15 to 29 years; males had higher rates of appendicitis than females at all ages except for 70 years and older. Appendicitis rates were 11.76 % higher in the summer than in the winter months. A multilevel analysis with hierarchical linear modeling (HLM) revealed that male patients, younger patients (aged ≤14 years), and elderly patients (aged ≥60 years) had a higher risk of perforated appendicitis; among adults, the incidence increased with age. Moreover, the risk of perforation was higher in patients with one or more comorbidities. LIP patients comprised 1.25 % of the total number of patients with appendicitis from 2000 to 2011. The overall incidence of appendicitis was 34.99 % higher in the LIP than in the normal population (NP), and the incidence of perforated appendicitis was 40.40 % higher in the LIP than in the NP. After multivariate adjustment, the adjusted hospital costs and length of hospital stay (LOS) for the LIP patients were higher than those for the NP patients. CONCLUSIONS: Appendicitis and appendectomy in Taiwan had similar overall incidences, seasonality patterns, and declining trends compared to numerous previous studies. Compared to NP patients, LIP patients had a higher risk of appendicitis, longer LOS and higher hospital costs as a result of appendectomy.

Epidemiology of appendicitis and appendectomy for the low-income population in Taiwan, 2003-2011.

BACKGROUND: Although numerous epidemiological studies on appendicitis have been conducted worldwide, only a few studies have paid attention to the effect of socioeconomic status on appendicitis, particularly studies focusing on the low-income population (LIP). METHODS: We analyzed the epidemiological features of appendicitis in Taiwan using data from the National Health Insurance Research Database from 2003 to 2011. All cases diagnosed as appendicitis were enrolled. RESULTS: Between 2003 and 2011, 2,916 patients from the LIP and 209,206 patients from the normal population (NP) were diagnosed with appendicitis. Our finding revealed that the ratios of comorbidities, complicated appendicitis, and readmissions in LIP patients were slightly higher than those of NP patients. LIP patients were more likely to live in suburban and rural areas, and hence a higher proportion of them were hospitalized in a district or regional hospital compared with NP patients. The crucially finding was that the overall incidence ratios of appendicitis, acute appendicitis, and perforated appendicitis in the LIP were substantially higher than those in the NP (36.25%, 35.33%, and 37.28%, respectively). The mean LOS in LIP patients was longer than that of NP patients. The overall case-fatality ratio of appendectomy in the LIP was higher when compared with the NP (0.41% versus 0.12%, p < 0.05). We also observed that appendicitis was occurred frequently in male patients, with a higher incidence for those aged 15-29 years in both the LIP and NP. The incidences of incidental appendectomy showed a decreasing trend in both the LIP and NP. Finally, a valuable discovery was that the total hospital cost was comparable between the laparoscopic appendectomy (LA) and open appendectomy (OA) (1,178 ± 13 USD versus 1,191 ± 19 USD, p < 0.05) in LIP patients because they saved more hospitalization costs than NP patients when the previous one chose the LA. CONCLUSION: This study confirmed that a lower socioeconomic status has significantly negative impact on the occurrence and treatment of appendicitis and appendectomy. In terms of hospital costs and LOS, LIP patients benefit more from the LA approach than they do from the OA approach in the treatment of appendicitis.

Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From Bench to Small and Large Animal Myocardial Ischemia Studies.

Cardiovascular disease is the leading cause of death globally, and stem cell therapy remains one of the most promising strategies for regeneration or repair of the damaged heart. We report that human placenta-derived multipotent cells (hPDMCs) can modulate cardiac injury in small and large animal models of myocardial ischemia (MI) and elucidate the mechanisms involved. We found that hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with mouse neonatal cardiomyocytes. Moreover, hPDMCs exert strong proangiogenic responses in vitro toward human endothelial cells mediated by secretion of hepatocyte growth factor, growth-regulated oncogene-α, and interleukin-8. To test the in vivo relevance of these results, small and large animal models of acute MI were induced in mice and minipigs, respectively, by permanent left anterior descending (LAD) artery ligation, followed by hPDMC or culture medium-only implantation with follow-up for up to 8 weeks. Transplantation of hPDMCs into mouse heart post-acute MI induction improved left ventricular function, with significantly enhanced vascularity in the cell-treated group. Furthermore, in minipigs post-acute MI induction, hPDMC transplantation significantly improved myocardial contractility compared to the control group (p = 0.016) at 8 weeks postinjury. In addition, tissue analysis confirmed that hPDMC transplantation induced increased vascularity, cardiomyogenic differentiation, and antiapoptotic effects. Our findings offer evidence that hPDMCs can modulate cardiac injury in both small and large animal models, possibly through proangiogenesis, cardiomyogenesis, and suppression of cardiomyocyte apoptosis. Our study offers mechanistic insights and preclinical evidence on using hPDMCs as a therapeutic strategy to treat severe cardiovascular diseases.

Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury.

Fibrosis of the peritoneal cavity remains a serious, life-threatening problem in the treatment of kidney failure with peritoneal dialysis. The mechanism of fibrosis remains unclear partly because the fibrogenic cells have not been identified with certainty. Recent studies have proposed mesothelial cells to be an important source of myofibroblasts through the epithelial-mesenchymal transition; however, confirmatory studies in vivo are lacking. Here, we show by inducible genetic fate mapping that type I collagen-producing submesothelial fibroblasts are specific progenitors of α-smooth muscle actin-positive myofibroblasts that accumulate progressively in models of peritoneal fibrosis induced by sodium hypochlorite, hyperglycemic dialysis solutions, or TGF-ß1. Similar genetic mapping of Wilms' tumor-1-positive mesothelial cells indicated that peritoneal membrane disruption is repaired and replaced by surviving mesothelial cells in peritoneal injury, and not by submesothelial fibroblasts. Although primary cultures of mesothelial cells or submesothelial fibroblasts each expressed α-smooth muscle actin under the influence of TGF-ß1, only submesothelial fibroblasts expressed α-smooth muscle actin after induction of peritoneal fibrosis in mice. Furthermore, pharmacologic inhibition of the PDGF receptor, which is expressed by submesothelial fibroblasts but not mesothelial cells, attenuated the peritoneal fibrosis but not the remesothelialization induced by hypochlorite. Thus, our data identify distinctive fates for injured mesothelial cells and submesothelial fibroblasts during peritoneal injury and fibrosis.

Cardiovascular Stem Cells in Regenerative Medicine: Ready for Prime Time?

Restoration of cardiovascular function is the ultimate goal of stem cell-based therapy. In principle, cardiovascular stem cells can improve cardiac function via de novo cardiomyogenesis, enhanced myocardial neovascularization, and prevention of post-infarct remodeling. Stem cell transplantation to improve cardiac function has received mixed results in human clinical trials. These early data suggest that a critical reassessment of the scientific basis to stem cell-based therapy is needed in order to bring this highly promising treatment modality to mainstream clinical care.