MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

OBJECTIVE: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. PATIENTS AND METHODS: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). RESULTS: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). CONCLUSION: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes

Successful support of biventricular heart failure patients by new EXCOR® Adult pumps with bileaflet valves: a prospective study

AIMS The Berlin Heart EXCORAdult biventricular assist device (BiVAD) is an approved mechanical circulatory support for patients with end-stage biventricular heart failure. In this prospective post-market clinical follow-up study, we present the first clinical experience of the new EXCORAdult pump with bileaflet (BL) valves in Europe. METHODS AND RESULTS After CE-mark approval in August 2014, a total of 12 patients were enrolled with a mean age of 44 years ± 11 (range 21-58 years). The majority of patients (n = 11) were in INTERMACS level 1 or 2. Eight patients had a median pre-operative extracorporeal life support (ECLS) of 6 days (range 1-37 days). Primary end point was survival, either to heart transplantation (HTx), recovery or alive at 12 months on device, whichever occurred first. Secondary end point was the number of adverse events throughout EXCORBiVAD support. Median support time up to last follow-up on EXCORBiVAD device was 248 days (range 57-381 days) and patient survival at 1 year was 92%. Half of the EXCORBiVAD patients (n = 6) were transplanted and five patients were still on support at 1 year post-implantation. Complications during EXCORBiVAD support were thoracic bleeding, exit site infection and ischemic cerebrovascular incidents in three cases, respectively. CONCLUSION The new EXCORAdult pump with BL provides pulsatile high cardiac output with excellent outcome and successful bridging to HTx, particularly in critically ill patients with INTERMACS level 1 or 2 at the time of implantation

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes