The inverse relationship between serum high-density lipoprotein cholesterol level and all-cause mortality in a 9.6-year follow-up study in the Japanese general population

In populations with higher high-density lipoprotein cholesterol (HDL-C) levels and lower coronary mortality than Western populations, such as in Japan, the beneficial effect of HDL-C on all-cause mortality may be different. Furthermore, prior studies have not focused on very high level of HDL-C. A total of 7175 community Japanese residents without a past history of cardiovascular disease in 300 randomly selected districts were followed for 9.6 years. During follow-up, there were 636 deaths. The multivariate adjusted hazard ratio (HR) of HDL-C for all-cause or cause-specific mortality was calculated using a Cox proportional hazard model adjusted for other cardiovascular risk factors. The all-cause mortality suggested an inverse, graded relation with HDL-C categories; HR for the very high HDL-C category (> or = 1.82 mmol/L), compared with the reference group (1.04-1.55 mmol/L), was 0.73 (95% confidence interval, C.I., 0.50-1.06) for men, 0.63 (95% C.I., 0.41-0.94) for women and 0.70 (95% C.I., 0.53-0.93) when men and women were combined. Serum HDL-C as a continuous variable showed a significant inverse association with all-cause mortality. The cardiovascular mortality indicated a non-significant but inverse graded relation with HDL-C categories. As in the many Western populations, serum HDL-C levels were inversely associated with all-cause mortality in the Japanese general population.     

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2‐skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox‐active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL‐13 and eotaxin production are decreased in TRX‐Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2‐type cytokines and Ig were detected in LN and serum, respectively, from TRX‐Tg and WT mice. Likewise, CD4⁺ T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX‐Tg and WT mice contained similar amounts of GATA‐3⁺ and Foxp3⁺ T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX‐Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.     

Galectin‐9 expands immunosuppressive macrophages to ameliorate T‐cell‐mediated lung inflammation

Galectin‐9 (Gal‐9) plays pivotal roles in the modulation of innate and adaptive immunity to suppress T‐cell‐mediated autoimmune models. However, it remains unclear if Gal‐9 plays a suppressive role for T‐cell function in non‐autoimmune disease models. We assessed the effects of Gal‐9 on experimental hypersensitivity pneumonitis induced by Trichosporon asahii. When Gal‐9 was given subcutaneously to C57BL/6 mice at the time of challenge with T. asahii, it significantly suppressed T. asahii‐induced lung inflammation, as the levels of IL‐1, IL‐6, IFN‐γ, and IL‐17 were significantly reduced in the BALF of Gal‐9‐treated mice. Moreover, co‐culture of anti‐CD3‐stimulated CD4 T cells with BALF cells harvested from Gal‐9‐treated mice on day 1 resulted in diminished CD4 T‐cell proliferation and decreased levels of IFN‐γ and IL‐17. CD11b⁺Ly‐6C^highF4/80⁺ BALF M? expanded by Gal‐9 were responsible for the suppression. We further found in vitro that Gal‐9, only in the presence of T. asahii, expands CD11b⁺Ly‐6C^highF4/80⁺ cells from BM cells, and the cells suppress T‐cell proliferation and IFN‐γ and IL‐17 production. The present results indicate that Gal‐9 expands immunosuppressive CD11b⁺Ly‐6C^high M? to ameliorate Th1/Th17 cell‐mediated hypersensitivity pneumonitis.     

A comparison of bone-patellar tendon-bone and bone-hamstring tendon-bone autografts for anterior cruciate ligament reconstruction

BACKGROUND: Most of the previous comparative studies between patellar tendon and hamstring tendon anterior cruciate ligament grafts compared grafts of different constructs fixed with different methods. PURPOSE: To compare patellar tendon and hamstring tendon grafts with the same fixation method used to reconstruct the anterior cruciate ligament. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: During the reconstructive procedure, the hamstring tendon graft was prepared as a bone-hamstring-bone graft; both bone-patellar tendon-bone and bone-hamstring-bone grafts were fixed with interference screws. Eighty consecutive patients who underwent anterior cruciate ligament reconstruction were randomly assigned to either bone-patellar tendon-bone or bone-hamstring-bone groups. Follow-up examinations were performed for at least 5 years postoperatively. Seventy-two of the 80 patients (37 patients in the bone-patellar tendon-bone group and 35 in the bone-hamstring-bone group) were evaluated, with a mean follow-up period of 87.0 and 80.8 months, respectively. Follow-up examinations were performed using the International Knee Documentation Committee knee ligament standard and subjective knee forms. RESULTS: The mean KT-1000 arthrometer evaluation results showed no significant difference between the bone-patellar tendon-bone and bone-hamstring-bone groups (1.2 +/- 2.1 mm and 1.7 +/- 1.4 mm, respectively; P = .24). However, symptoms related to graft harvest (anterior kneeling pain) were more frequently observed in the bone-patellar tendon-bone group, and unsatisfactory results were correlated with severe kneeling pain in 3 patients from this group (P = .0056). Significant hamstring muscle weakness without complaint of functional deficit was found in the bone-hamstring-bone group (P = .0045). CONCLUSION: Bone-hamstring-bone grafts were shown to reduce the risk of problems at the graft harvest site compared to bone-patellar tendon-bone grafts, with comparable results in the remaining clinical parameters tested.     

Assessment of diabetic retinopathy using two ultra-wide-field fundus imaging systems,the Clarus® and Optos™ systems

Background

The ability to image wide fundus fields and to conduct swift, non-invasive examinations is increasingly important with the escalation in patients with diabetic retinopathy (DR).

Methods

Fifty eyes of 28 consecutive patients with DR were examined in this prospective observational study. A total of 46 eyes, 25 right and 21 left eyes, of 27 patients (male, 19; female, 8) were ultimately included in the analysis. All patients underwent comprehensive ophthalmological examination. A single image each was obtained using two ultra-wide-field (UWF) imaging systems: Optos® (Optos Carfornia®, Optos PLC, Dunfermline, United Kingdom) and Clarus? (CLARUS 500?, Carl Zeiss Meditec Inc., Californea, USA), without mydriasis. The total retinal area captured and the obscured retinal area were compared between the two systems using nonparametric Wilcoxon matched-pairs signed-rank analysis. Early Treatment of Diabetic Retinopathy Study (ETDRS) and International Clinical DR severity were analyzed by κ statistics.

Results

The Optos® allowed capture of larger areas of the fundus than the Clarus? (465?±?117 vs. 243?±?39 disc areas, P <?0.0001). In 85% (39/46) of Optos® images and 7% (3/46) of Clarus? images, a slightly obscured area was observed within the ETDRS-7 field area. κ values for ETDRS DR severity and International Clinical DR severity between the Optos® and Clarus? images were 0.88 and 0.79, respectively. Severity was higher according to Clarus? images in two eyes in which the ETDRS DR severity grading differed between the systems. Severity was higher in four Clarus? images and in a single Optos® image in five eyes in which the International Clinical DR severity grading differed between the systems.

Conclusion

The Optos® and Clarus? UWF retinal imaging systems were useful for examining eyes with DR, using single images obtained without mydriasis. The systems were both generally consistent in assessing DR severity, with some partial discrepancies. It is important to understand the characteristics of each respective UWF retinal imaging system when using them to assess DR.

     

Pre-treatment with proton pump inhibitors decreases the success of primary Helicobacter pylori eradication using a vonoprazan-based regimen

Vonoprazan-based regimens have improved the rate of successful Helicobacter pylori (H. pylori) eradication, but it has not reached 100%. The aim of this study is to clarify significant predictors of successful H. pylori eradication using a vonoprazan-based regimen. In this retrospective cohort study, 174 patients who underwent primary H. pylori eradication therapy were included. All patients underwent esophagogastroduodenoscopy before treatment. The vonoprazan-based regimen includes amoxicillin 750 mg, clarithromycin 200 mg and vonoprazan 20 mg twice daily for one week. Pre-treatment with a proton pump inhibitor (PPI) was defined as continued PPI use for more than four weeks prior to eradication therapy. The rates of successful eradication were 83% (145/174) in intention-to-treat analysis and 85% (145/171) in per-protocol analysis. Predictors of successful eradication among 171 patients were evaluated in per-protocol analysis. In univariate analysis, male gender was a significant positive predictor of successful eradication (odds ratio [OR] 3.813, 95% confidence interval [CI] 1.363–10.663, p = 0.010) and pre-treatment with PPIs was a negative predictor (OR 0.193, 95%CI 0.076–0.485, p < 0.001). In multivariate analysis, male gender remained a positive predictor (OR 3.826, 95%CI 1.317–11.116, p = 0.013), and pre-treatment with PPIs (OR 0.232, 95%CI 0.087–0.615, p = 0.003) remained a negative predictor. In conclusion, pre-treatment with PPIs before eradication therapy decreases the rate of successful eradication. Therefore, it may be desirable to discontinue pre-treatment with PPIs prior to eradication therapy, because of the potential to improve the rate of successful eradication.