The production and roles of endogenous gamma interferon (IFN-␥), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in both lethal and nonlethal infections of Staphylococcus aureus were investigated in mice. In the case of nonlethal infection, although no bacteria were detected in the bloodstreams, bacteria that colonized and proliferated persistently for 3 weeks were found in the kidneys. All mice given lethal injections died within 7 days, and large numbers of bacteria were detected in the bloodstreams, spleens, and kidneys. The first peaks of IFN-␥, TNF, and IL-6 were observed in the bloodstreams and spleens of the mice with nonlethal and lethal infections within 24 h. Thereafter, in the nonlethal cases, IFN-␥, TNF, and IL-6 peaked again in the spleens and kidneys during the period of maximum growth of bacteria in the kidneys, although only IL-6 was detected in the sera. In contrast, in the case of lethal infection, the titers of IFN-␥ and IL-6 in the sera and TNF in the kidneys peaked before death. Effects of in vivo administration of monoclonal antibodies (MAbs) against IFN-␥ and TNF on the fates of S. aureus-infected mice were studied. In the nonlethal infections, anti-TNF alpha (anti-TNF-␣) MAb-treated mice, but not anti-IFN-␥ MAb-treated mice, died as a result of worsening infection, suggesting that endogenous TNF plays a protective role in host resistance to S. aureus infection. In the mice that received lethal doses, injection of anti-TNF-␣ MAb accelerated death. However, although injection of anti-IFN-␥ MAb inhibited host resistance of the infected mice early in infection, most of the animals survived the lethal infection by injection of anti-IFN-␥ MAb, suggesting that endogenous IFN-␥ plays a detrimental role in S. aureus infection. Thus, this study demonstrated that IFN-␥ and TNF play different roles in S. aureus infection.

Introduction: The left atrial (LA) posterior wall (LAPW) has been targeted to improve the clinical outcomes in patients with persistent atrial fibrillation (PersAF). This study aimed to investigate the feasibility, safety, and clinical implications of cryoballoon (CB) applications on the LAPW to accomplish electrical isolation (EI) of the LAPW with CB.Methods: A total of 100 patients (males, 84; mean age, 64 ± 10 years) with PersAF were enrolled. The first 50 patients underwent only pulmonary vein isolation (PVI) (PVI-only group) and the remaining 50 patients underwent PVI and EI of the LAPW with CB (EI-LAPW group). Results:One-year sinus rhythm maintenance probability was significantly higher in the EI-LAPW group than in PVI-only group (80.0% vs 55.1%, P = 0.01). The success rate of constructing an LA roof block line (LA-RB), bottom block line, and EI of the LAPW was 92%, 60%, and 58%, respectively. The nadir CB temperature (−45°C ± 4°C vs −39°C ± 5°C, P = 0.005) and anatomical angle of the left atrial roof (106°C ± 30°C vs 144°C ± 17°C, P < 0.001) significantly predicted the successful LA-RB construction.The left ventricular ejection fraction was significantly higher in unsuccessful cases than in successful cases of an EI of the LAPW (64% ± 8% vs 58% ± 11%, P = 0.041).Even though the EI of the LAPW was unsuccessful, CB freezing in LAPW significantly debulked the nonscar area (≥0.1 mV) in LAPW (18.1 ± 5.6 vs 2.2 ± 3.1 cm 2 , P < 0.001) and provided the equivalent 1-year outcome of successful cases (79.3% vs 81.0%, P = 0.90). Conclusion:The combination of PVI and EI of the LAPW with CB provided better clinical outcomes than conventional PVI procedure for patients with PersAF. K E Y W O R D S atrial fibrillation, cryoballoon, electrical isolation of left atrial posterior wall J Cardiovasc Electrophysiol. 2019;30:805-814.wileyonlinelibrary.com/journal/jce

Background: Vascular access (VA) guidelines recommend the native arteriovenous fistula (AVF) as VA of first choice for chronic hemodialysis patients. AVF management is important in hemodialysis patient care. AVF survival is associated with various physical factors, but the effects of dialysis treatment factors upon AVF survival are still not clear. Methods: Study patients were treated at 498 dialysis facilities participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) 2 or 3 (2002-2007). Analyses included 1,183 incident hemodialysis patients (on dialysis ≤7 days and using an AVF at study entry) and 949 prevalent patients (on dialysis >7 days at DOPPS entry and using a new AVF created during study observation). AVF survival was modeled from the study entry date for incident patients and date of first AVF use for prevalent patients. Predictors of primary and final AVF survival were compared across Japan, North America and Europe/Australia/New Zealand (EUR/ANZ) with adjustments for patient characteristics. Results: No meaningful relationship was seen between AVF survival and various physician and staff practices. However, patients with prior catheter use displayed higher rates of primary and final AVF failure. Final AVF failure rates were higher in facilities with higher median blood flow rates (BFR). They were also greater in North America and EUR/ANZ than in Japan, but this difference was substantially attenuated after accounting for regional differences in facility median BFR. Conclusion: AVF longevity differed according to the DOPPS region, and was related to prior patient catheter use and facility BFR practice. Further longitudinal studies may help demonstrate meaningful associations between VA-handling skill and patency.

The long-term clinical outcomes of ablation of AF with the CB was worse in patients with an LCPV than in those without. The presence of an LCPV and the LA size seemed to be reliable predictors of a worse outcome.

The production and roles of endogenous interleukin-4 (IL-4) and IL-10 in a sublethal infection with Listeria monocytogenes were studied in normal mice and anti-gamma interferon (IFN-␥) monoclonal antibody (MAb)pretreated mice. In normal mice, the expression of mRNAs for IL-4 and IL-10, which was amplified by reverse transcription-PCR, was induced in the spleens and livers either early or late in infection, although the serum IL-4 and IL-10 were not detectable by enzyme-linked immunosorbent assays. In vivo administration of anti-IL-4 MAb showed no effect on antilisterial resistance, whereas anti-IL-10 MAb partially diminished the defense. In anti-IFN-␥ MAb-pretreated mice, a delay in the bacterial elimination from the spleens and livers was observed and high titers of serum IL-4 and IL-10 were induced late in infection. Production of endogenous IL-4 and IL-10 was suppressed in both CD4 ؉ cell-and CD8 ؉ cell-depleted mice. The suppression of antilisterial resistance in anti-IFN-␥ MAb-pretreated mice was canceled when anti-IL-4 MAb was injected late in infection, whereas anti-IL-10 MAb showed no effect. These results suggest that the host immune responses were polarized into the T-helper 2 phenotype in anti-IFN-␥ MAb-pretreated mice and that inhibition of host resistance against L. monocytogenes by depletion of IFN-␥ might be attributable to IL-4 produced by T cells polarized into the T-helper 2 phenotype as well as the inhibition of the IFN-␥ effects.

This study showed a significant difference in tumour characteristics and treatment patterns in patients aged 80 and above. Even after adjustment for clinicopathological factors, the difference in survival persisted and age was considered a robust prognostic factor.

It has been presumed that gamma interferon (IFN-gamma), which plays an essential role in antilisterial resistance, is produced late in Listeria monocytogenes infection. In the present study, however, IFN-gamma was detected in the bloodstreams and spleens of mice from days 1 to 4 of L. monocytogenes infection by both a double-sandwich enzyme-linked immunosorbent assay and an immunohistochemical technique, suggesting that endogenous IFN-gamma is produced early but not late in L. monocytogenes infection.

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