Background. The role of the innate immune system in the development of thrombotic microangiopathy (TM) after α1,3-galactosyltransferase gene-knockout (GTKO) pig organ transplantation in primates is uncertain. Methods. Twelve organs (nine hearts, three kidneys) from GTKO pigs were transplanted into baboons that received no immunosuppressive therapy, partial regimens, or a full regimen based on costimulation blockade. After graft failure, histologic and immunohistologic examinations were carried out. Results. Graft survival of less than 1 day was prolonged to 2 to 12 days with partial regimens (acute humoral xenograft rejection) and to 5 and 8 weeks with the full regimen (TM). Clinical or laboratory features of consumptive coagulopathy occurred in 7 of 12 baboons. Immunohistochemistry demonstrated IgM, IgG, and complement deposition in most cases. Histopathology demonstrated neutrophil and macrophage infiltrates, intravascular fibrin deposition, and platelet aggregation (TM). Grafts showed expression of primate tissue factor (TF), with increased mRNA levels, and TF was also expressed on baboon macrophages/monocytes infiltrating the graft. Conclusions. Our data suggest that (1) irrespective of the presence or absence of the adaptive immune response, early or late xenograft rejection is associated with activation of the innate immune system; and (2) porcine endothelial cell activation and primate TF expression by recipient innate immune cells may both contribute to the development of TM.

Background. Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft-tissue infection that is traditionally caused by group A Streptococcus (GAS) or mixed aerobic/anaerobic bacteria. Monomicrobial Klebsiella pneumoniae NF (KP-NF) has been reported since 1996 but has not yet been systematically studied. Methods. We retrospectively studied consecutive NF cases treated at a university hospital in Taiwan during 1997–2010 and investigated the clinical characteristics and outcomes associated with monomicrobial KP-NF, using monomicrobial GAS-NF as a reference. We also analyzed the virulence gene profiles of the isolated K. pneumoniae strains. Results. Of 134 NF cases, 88 were monomicrobial, of which the most common pathogens were GAS (n = 16) and K. pneumoniae (n = 15). Monomicrobial KP-NF entailed a moderate risk of limb loss (20% vs 25%; P = 1.000) and high mortality (47% vs 19%; P = .135), and it was more likely to involve bacteremia (80% vs 31%; P = .011), concomitant distant abscesses (27% vs 0%; P = .043), and underlying immunocompromising conditions (100% vs 63%; P = .018), compared with GAS-NF. The isolated K. pneumoniae strains (n = 10) were of capsular polysaccharides genotype K1 (n = 4), K54/K20/K5 (n = 4), K2 (n = 1), and K16 (n = 1). All strains carried rmpA, iucABCDiutA, and iroA. Genotype K1 strains had a significantly higher risk of concomitant distant abscesses, compared with non-K1 strains (75% vs 0%; P = .033). Conclusions. K. pneumoniae has become a common pathogen of monomicrobial NF in Taiwan. Physicians treating patients with monomicrobial KP-NF should be aware of the risk of concomitant distant abscesses, particularly in cases caused by genotype K1.

Necrotizing fasciitis (NF) is a rapidly progressive and life-threatening infection. This study aimed to investigate the clinical characteristics and mortality- associated factors in diabetic patients. Detailed clinical information of 165 NF cases was retrospectively collected and analyzed in National Taiwan University Hospital between January 1997 and February 2013. We documented and compared the clinical features according to the presence of underlying diabetes mellitus, and we identified risk factors associated with mortality. There were 84 patients (51 %) with diabetes. The overall case fatality rate was 29.7 %, and we found no significant difference between the patients with or without diabetes. Compared with the nondiabetic patients, diabetic patients were older and exhibited higher serum levels of glucose and potassium on admission. Polymicrobial infection and monomicrobial NF caused by Klebsiella pneumoniae were also more frequently associated with diabetic patients. Moreover, diabetic NF patients exhibit a significantly higher chance of limb loss during hospitalization. In the combined diabetic and nondiabetic cohort, a high serum level of potassium (odds ratio, 2.2; 95 % confidence interval, 1.2 to 4.02; P = 0.011) on admission was independently associated with mortality, whereas positive blood culture on admission was associated with mortality in the diabetic cohort (odds ratio, 7.36; 95 % confidence interval, 1.66 to 32.54; P = 0.009). Diabetic patients are more susceptible to NF caused by polymicrobial infection or K. pneumoniae, and they are more likely to receive limb amputation for infection control. Bacteraemia on admission is a significant risk factor for mortality in diabetic NF patients.

Although human complement-dependent cytotoxicity (CDC) of α1,3-galactosyltransferase gene-knockout (GTKO) pig cells is significantly weaker than that of wild-type (WT) cells, successful xenotransplantation will require pigs with multiple genetic modifications. Sera from healthy humans were tested by (i) flow cytometry for binding of IgM/IgG, and (ii) CDC assay against peripheral blood mononuclear cells and porcine aortic endothelial cells from five types of pig – WT, GTKO, GTKO transgenic for H-transferase (GTKO/HT), WT transgenic for human complement regulatory protein CD46 (CD46) and GTKO/CD46. There was significantly higher mean IgM/IgG binding to WT and CD46 cells than to GTKO, GTKO/HT, and GTKO/CD46, but no difference between GTKO, GTKO/HT, and GTKO/CD46 cells. There was significantly higher mean CDC to WT than to GTKO, GTKO/HT, CD46, and GTKO/CD46 cells, but no difference between GTKO and GTKO/HT. Lysis of GTKO/CD46 cells was significantly lower than that of GTKO or CD46 cells. CD46 expression provided partial protection against serum from a baboon sensitized to a GTKO pig heart. GTKO/CD46 cells were significantly resistant to lysis by human serum and sensitized baboon serum. In conclusion, the greatest protection from CDC was obtained by the combination of an absence of Gal expression and the presence of CD46 expression, but the expression of HT appeared to offer no advantage over GTKO. Organs from GTKO/CD46 pigs are likely to be significantly less susceptible to CDC.

Background: There are over 2 million newly diagnosed patients with breast cancer worldwide with more than 10,000 cases in Taiwan each year. During 2017-2018, the National Yang-Ming University, the Taiwan University of Science and Technology, and the Taiwan Breast Cancer Prevention Foundation collaborated to develop a breast cancer self-management support (BCSMS) mHealth app for Taiwanese women with breast cancer.Objective: The aim of this study was to investigate the quality of life (QoL) of women with breast cancer in Taiwan after using the BCSMS app.Methods: After receiving a first diagnosis of breast cancer, women with stage 0 to III breast cancer, who were recruited from social networking sites or referred by their oncologists or oncology case managers, were randomized 1:1 into intervention and control groups. Intervention group subjects used the BCSMS app and the control group subjects received usual care. Two questionnaires—the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and the EORTC Breast Cancer-Specific Quality-of-Life Questionnaire (QLQ-BR23)—were distributed to subjects in both arms. Paper-based questionnaires were used at baseline; paper-based or Web-based questionnaires were used at 1.5-month and 3-month follow-up evaluations. All evaluations were self-assessed and anonymous, and participants were blinded to their allocation groups. Descriptive analysis, the Pearson chi-square test, analysis of variance, and the generalized estimating equation were used to analyze the data. Missing values, with and without multi-imputation techniques, were used for sensitivity analysis.Results: A total of 112 women were enrolled and randomly allocated to either the experimental group (n=53) or control group (n=59). The follow-up completion rate was 89.3% (100/112). The demographic data showed homogeneity between the two groups in age (range 50-64 years), breast cancer stage (stage II), marital status (married), working status (employed), and treatment status (receiving treatments). The mean total QoL summary scores from the QLQ-C30 (83.45 vs 82.23, P=.03) and the QLQ-BR23 (65.53 vs 63.13, P=.04) were significantly higher among the experimental group versus the control group, respectively, at 3 months.Conclusions: This research provides support for using a mobile health care app to promote the QoL among women in Taiwan after a first diagnosis of breast cancer. The BCSMS app could be used to support disease self-management, and further evaluation of whether QoL is sustained is warranted.Trial Registration: ClinicalTrials.gov NCT004174248; https://clinicaltrials.gov/ct2/show/NCT04174248