Postoperative atrial fibrillation (POAF) after cardiac surgery is associated with longer hospital stay and increased in-hospital death and stroke, but its long-term implications remain incompletely ...understood. A systematic literature review was undertaken to investigate the impact of POAF on long-term death and stroke in adult patients who undergo cardiac operations.
Electronic databases (Cochrane, Embase, Ovid MEDLINE, and PubMed) were queried from inception to October 2018. Included studies compared long-term outcomes after cardiac operations in patients with and without POAF. Adjusted and unadjusted meta-analyses examined death, stroke, and major adverse cardiac and cerebrovascular events. Risk of bias was evaluated with the Newcastle-Ottawa Scale.
The inclusion criteria were met by 32 studies describing 155,575 patients who had undergone cardiac operations. POAF occurred in 36,988 patients (23.7%). Meta-analysis of 10 studies (44,367 patients) demonstrated increased 1-year death in patients with POAF (odds ratio, 2.60; 95% confidence interval, 2-3.38; P < .01). Aggregate adjusted hazard of death (16 studies, n = 84,295) was also increased in patients with POAF (hazard ratio, 1.25; 95% confidence interval, 1.2-1.3; P < .01).
This systematic review and meta-analysis identified an association between POAF and long-term death after cardiac surgery. More comprehensive POAF prevention and management, including more stringent follow-up for POAF recurrence after hospital discharge, may be indicated. The included studies used inconsistent definitions of POAF and variable exclusion criteria; however, estimates of heterogeneity are low. Differences in preoperative comorbidities, such as age, ejection fraction, and obesity, may not be fully accounted for in adjusted analyses. Future work is required to delineate mechanisms linking POAF and death in this population.
Androgen receptor splicing variants (ARVs) that lack the ligand-binding domain (LBD) are associated with the development of castration-resistant prostate cancer (CRPC), including resistance to the ...new generation of high-affinity anti-androgens. However, the mechanism by which ARV expression is regulated is not fully understood. In this study, we show that the activation of classical nuclear factor-kappa B (NF-κB) signaling increases the expression of ARVs in prostate cancer (PCa) cells and converts androgen-sensitive PCa cells to become androgen-insensitive, whereas downregulation of NF-κB signaling inhibits ARV expression and restores responsiveness of CRPC to anti-androgen therapy. In addition, we demonstrated that combination of anti-androgen with NF-κB-targeted therapy inhibits efficiently tumor growth of human CRPC xenografts. These results indicate that induction of ARVs by activated NF-κB signaling in PCa cells is a critical mechanism by which the PCa progresses to CRPC. This has important implications as it can prolong the survival of CRPC patients by restoring the tumors to once again respond to conventional androgen-deprivation therapy (ADT).
FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab.
WJOG4407G was a randomized, ...open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396.
Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively HR, 0.905; 95% confidence interval (CI) 0.723–1.133; P = 0.003 for non-inferiority. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785–1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months.
FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC.
UMIN000001396.
Oceanic core complexes (OCCs) represent tectonic windows into the oceanic lower crust and mantle; they are key structures in understanding the tectono‐magmatic processes shaping the oceanic ...lithosphere. We present a petrological and geochemical study of gabbros collected at the Mado Megamullion, a recently discovered OCC located in the extinct Shikoku back‐arc basin. Bathymetry of the Mado Megamullion reveals spreading‐parallel corrugations extending 25 km from the breakaway to the termination. Samples from several locations include peridotites, gabbros, dolerite, and rare pillow basalts. Gabbros range from granular to varitextured olivine gabbros and oxide gabbros. The emplacement of these gabbroic rocks within the oceanic lithosphere was followed by a multiphase tectono‐metamorphic evolution including (i) dynamic recrystallization within shear zones, developed under granulite‐ to upper‐amphibolite‐facies conditions, and (ii) intrusion of highly evolved melts forming felsic segregations. This tectono‐metamorphic evolution recalls that of the lower crust from other OCCs worldwide, demonstrating that this OCC exposes deep‐seated intrusions progressively exhumed by detachment faulting. Nonetheless, the Mado Megamullion lower crustal gabbros show an unusual crystal line of descent, different from what is reported from mid‐ocean ridge lower crustal rocks. We infer that the water‐bearing character of the primary melts in this back‐arc basin triggered the early precipitation of clinopyroxene, soon followed by amphibole and Fe‐Ti oxides. Such modifications in phase saturation are likely to be directly related to the back‐arc setting of the Mado Megamullion. If so, the phase assemblages of oceanic gabbros may be a diagnostic for the tectonic setting of lower crustal rocks in ophiolites.
Key Points
The tectono‐magmatic evolution recorded at the Mado Megamullion recalls that of mid‐ocean ridge oceanic core complexes
Lower oceanic crust in back‐arc basins shows a distinctive crystal line of descent triggered by the water‐rich character of the melt
Phase assemblages in oceanic gabbros can be used as a diagnostic for the tectonic setting of formation of lower crustal rocks in ophiolites
To cite this article: Yamashita H, Takahashi K, Tanaka H, Nagai H, Inagaki N. Overcoming food allergy through acquired tolerance conferred by transfer of Tregs in a murine model. Allergy 2012; 67: ...201–209.
Background: The number of food allergy patients is increasing. Some children outgrow their food allergies through tolerance, whereas others remain susceptible throughout their lives. We aimed to contribute to food allergy therapeutics by understanding induction of oral tolerance in a murine food allergy model.
Methods: We modified an existing murine food allergy model by using ovalbumin (OVA) to induce oral tolerance, either by pretreating mice with OVA or by transferring mesenteric lymph node (MLN) cells or T cells derived from mice treated with OVA.
Results: Pretreatment with OVA prevented food allergy, with complete suppression of OVA‐specific immunoglobulin (Ig)E and IgA antibody production and interleukin (IL)‐4, IL‐10, and IL‐9 mRNA expression. The proportion of regulatory T cells (Tregs) in MLN cells and expression of transforming growth factor‐β mRNA increased. In the transfer model, anaphylaxis secondary to OVA intake was suppressed by transfer of whole MLN cells and Tregs from OVA‐treated mice. However, OVA‐specific IgE and IgA expressions were partially attenuated by transfer of antigen‐specific and nonspecific Tregs, but not by whole MLN cells from OVA‐treated mice. In the Treg transfer model, IL‐4 and IL‐10 mRNA expression decreased, but IL‐9 mRNA expression increased.
Conclusion: We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy.
Amakusa Daioh cross chickens from Kumamoto Prefecture, Kyushu Island, Japan, are F1 hybrid chickens resulting from a cross between the Amakusa Daioh and Kyushu Rhode breeds. A significant association ...has been reported between a SNP (AB604331, g.420 C>A) in the cholecystokinin type A receptor gene and growth traits in some Japanese slow-growing chickens. This genetic improvement effect was examined in Amakusa Daioh cross chickens by comparing superior A allele-fixed chickens with conventional ones. Fattening experiments using 436 conventional and 297 improved (A allele-fixed) Amakusa Daioh cross birds were performed over two seasons. In each season, experimental birds of both sexes were hatched on the same day, raised in the same chicken house, and fed the same diet ad libitum for 15 wk for cockerels and 19 wk for pullets, after which they were slaughtered. Body weight (BW), average daily gain (ADG), and carcass weights were measured. SNP genotypes were determined using mismatch amplification mutation assay. Association between the SNP and growth traits was analyzed using GLM, taking into account gender, season, genetic additive and dominance, and test group effects. The improved pullets were significantly heavier than the conventional pullets at slaughter age. Boneless carcasses of the improved pullets were significantly heavier than those of the conventional pullets as well. In the conventional cockerels, significantly positive additive effects of the A allele on BW were detected during the entire experimental period, except at 10 and 11 wk. Significantly positive additive effects of the A allele on thigh weight were detected. We concluded that g.420 C>A is a good selective marker for increased slaughter live weight and meat weight in Amakusa Daioh cross chickens.
Coral–algal symbioses are essential for the survival of corals. Algal endosymbionts, specifically the dinoflagellate genus
Symbiodinium
, are divided into several genetic clades. The composition of
...Symbiodinium
within corals plays an important role in the tolerance and/or sensitivity of host corals to local environments, due to individual
Symbiodinium
-specific physiological characteristics. While the majority of gamete-spawning corals acquire
Symbiodinium
from the surrounding environment, little is known about whether corals specifically select or randomly acquire
Symbiodinium
from the environmental population. In the present study, we compared the
Symbiodinium
clade composition of newly recruited
Acropora
corals with that of the environmental pool (water column, sediments, and adult colonies). More than 90 % of recruits harbored clades A and/or D until 6 months after settlement, despite the
Symbiodinium
environmental pool being mainly composed of clade C (mainly ITS1 type C2), and to a lesser extent clades A and D. In addition, the environmentally dominant type C2
Symbiodinium
was not detected in
Acropora
recruits, while a few recruits harbored ITS1 types C1 or C15. Therefore, the clade composition of recruits may not reflect the abundance/density of
Symbiodinium
populations in the environment. Some members of clades A and D are known to exhibit tolerance to a wide range of environments. ITS1 type C1 also exhibits greater tolerance to thermal stress compared to ITS1 type C2. These tolerance characteristics of certain
Symbiodinium
may be vital for the initial survival of
Acropora
recruits, even if these
Symbiodinium
are rare in the environment.
Background: A phase II study to evaluate the efficacy and tolerability of weekly i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric cancer patients with peritoneal ...metastasis. Patients and methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m2 and i.p. at 20 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1–23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%). Conclusion: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.
Summary
Background
Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid ...consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur.
Objective
We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives.
Methods
We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea.
Results
Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA‐specific IgE were induced in the murine model of oral tolerance. Analyses of antigen‐presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25hi regulatory T cells among CD4+ T cells in the mesenteric lymph nodes.
Conclusions and Clinical Relevance
A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies.
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