Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation.

Objectives To investigate the incidence of active tuberculosis (TB) among COPD patients using fluticasone/salmeterol or budesonide/formoterol, and to identify any differences between these two groups of patients. Methods The study enrolled COPD patients from Taiwan NHIRD who received treatment with fluticasone/salmeterol or budesonide/formoterol for > 90 days between 2004 and 2011. The incidence of active TB was the primary outcome. Results Among the intention-to-treat population prior to matching, the incidence rates of active TB were 0.94 and 0.61% in the fluticasone/salmeterol and budesonide/formoterol groups, respectively. After matching, the fluticasone/salmeterol group had significantly higher rates of active TB (adjusted HR, 1.41, 95% CI, 1.17–1.70) compared with the budesonide/formoterol group. The significant difference between these two groups remained after a competing risk analysis (HR, 1.45, 95% CI, 1.21–1.74). Following propensity score matching, the fluticasone/salmeterol group had significantly higher rates of active TB compared with the budesonide/formoterol group (adjusted HR, 1.45, 95% CI, 1.14–1.85). A similar trend was observed after a competing risk analysis (HR, 1.44, 95% CI, 1.19–1.75). A higher risk of active TB was observed in the fluticasone/salmeterol group compared with the budesonide/formoterol group across all subgroups, but some differences did not reach statistical significance. Conclusion Fluticasone/salmeterol carried a higher risk of active TB compared with budesonide/formoterol among COPD patients.

The coronavirus disease (COVID-19) is a novel emerging infectious disease spreading worldwide. To further understand the disease, we compared its clinical characteristics, symptoms, and outcomes by gender. In an analysis of public surveillance data of Taiwan from January 21 to April 18, 2020, a total of 398 patients were diagnosed with COVID-19 by the detection of severe acute respiratory syndrome coronavirus 2 in pharynx swabs. We divided the patients into two groups: men and women. The associated data were collected, and multivariate comparisons of radiographic infiltration were conducted to analyze the gender-based differences. The mean incubation period was 5.4±5 days, and the incubation period in men was 3.2 days longer than that in women (8±8.1 vs. 4.8±3, p=0.05). The male patients with COVID-19 with infiltration in chest X-rays (CXR) were 12 years older than their female counterparts. The mortality rate in the male patients with COVID-19 was 6.4-fold higher than that in the female patients (3.2% vs. 0.5%, p<0.05). The patients with co-morbidities of diabetes mellitus and hypertension were vulnerable to infiltration in CXR, and the patients with COVID-19 who had infiltration in CXR easily ended up with intubation, intensive care unit admission, and mortality. Moreover, female patients with COVID-19 who had fever, cough, and dyspnea were susceptible to infiltration in CXR. Irrespective of whether the cases were imported female from Europe, America, or Asia, indigenous male, the factors associated with death in patients with severe COVID-19 were male sex, elderly, female with fever, cough, dyspnea and DM.

Background The successful management of patients infected with coronavirus disease 2019 (COVID-19) with inhaled ciclesonide has been reported, however few studies have investigated its application among hospitalized patients. Methods This retrospective cohort study enrolled all adult patients admitted to our hospital with confirmed COVID-19 infection from May to June 2021. Critical patients who received mechanical ventilation within 24 h after admission and those who started ciclesonide more than 14 days after symptom onset were excluded. The in-hospital mortality rate was compared between those who did and did not receive inhaled ciclesonide. Results A total of 269 patients were enrolled, of whom 184 received inhaled ciclesonide and 85 did not. The use of ciclesonide was associated with lower in-hospital mortality (7.6% vs. 23.5%, p = 0.0003) and a trend of shorter hospital stay (12.0 (10.0–18.0) days vs. 13.0 (10.0–25.3) days, p = 0.0577). In subgroup analysis, the use of inhaled ciclesonide significantly reduced mortality in the patients with severe COVID-19 infection (6.8% vs. 50.0%, p < 0.0001) and in those with a high risk of mortality (16.4% vs. 43.2%, p = 0.0037). The use of inhaled ciclesonide also reduced the likelihood of receiving mechanical ventilation in the patients with severe COVID-19 infection. After multivariate analysis, inhaled ciclesonide remained positively correlated with a lower risk of in-hospital mortality (odds ratio: 0.2724, 95% confidence interval: 0.087–0.8763, p = 0.0291). Conclusions The use of inhaled ciclesonide in hospitalized patients with COVID-19 infection can reduce in-hospital mortality. Further randomized studies in patients with moderate to severe COVID-19 infection are urgently needed.