Lumen Loss at 1 Year After Bare Nitinol Stent Implantation in the Superficial Femoral Artery.

PURPOSE: To investigate lumen loss (LL) at 1 year after bare nitinol stent (BNS) implantation for de novo superficial femoral artery (SFA) lesions. MATERIALS AND METHODS: The subjects were 701 consecutive patients (mean age 74±9 years; 492 men) with 817 de novo SFA lesions treated with BNS implantation between January 2004 and September 2015. The mean lesion length was 141±88 mm and the mean vessel diameter was 5.4±0.9 mm. The endpoint was LL at 1 year after BNS implantation. Secondary outcomes were restenosis and target lesion revascularization (TLR) estimated using the Kaplan-Meier method; estimates are reported with the 95% confidence interval (CI). LL was defined as the minimum lumen diameter immediately after BNS implantation minus that at 1 year measured by angiographic quantitative vessel analysis. The distribution of LL in the overall population was estimated using an accelerated failure time model. RESULTS: Mean LL at 1 year was estimated to be 1.74±1.28 mm (95% CI 1.63 to 1.84). Current smoking was positively associated with LL (p=0.015), whereas lack of cilostazol use was correlated with an increase in LL (p=0.001). Reference vessel diameter and lesion length did not have any significant association with LL at 1 year. The 1-year cumulative estimate of restenosis was 25% (95% CI 22% to 28%); the corresponding value for TLR was 18% (95% CI 15% to 21%). CONCLUSION: Mean LL progressed by at least 1.6 mm up to 1 year after BNS implantation. The risk factors for increased LL were current smoker and lack of cilostazol use.

Structural and Functional Basis for LILRB Immune Checkpoint Receptor Recognition of HLA-G Isoforms.

Human leukocyte Ig-like receptors (LILR) LILRB1 and LILRB2 are immune checkpoint receptors that regulate a wide range of physiological responses by binding to diverse ligands, including HLA-G. HLA-G is exclusively expressed in the placenta, some immunoregulatory cells, and tumors and has several unique isoforms. However, the recognition of HLA-G isoforms by LILRs is poorly understood. In this study, we characterized LILR binding to the ß2-microglobulin (ß2m)-free HLA-G1 isoform, which is synthesized by placental trophoblast cells and tends to dimerize and multimerize. The multimerized ß2m-free HLA-G1 dimer lacked detectable affinity for LILRB1, but bound strongly to LILRB2. We also determined the crystal structure of the LILRB1 and HLA-G1 complex, which adopted the typical structure of a classical HLA class I complex. LILRB1 exhibits flexible binding modes with the α3 domain, but maintains tight contacts with ß2m, thus accounting for ß2m-dependent binding. Notably, both LILRB1 and B2 are oriented at suitable angles to permit efficient signaling upon complex formation with HLA-G1 dimers. These structural and functional features of ligand recognition by LILRs provide novel insights into their important roles in the biological regulations.

Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). METHODS: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. RESULTS: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. CONCLUSIONS: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

Novel Xyloglucan Sheet for the Treatment of Deep Wounds: Preparation, Physicochemical Characteristics, and in Vivo Healing Effects.

In the present study, a novel wound dressing made of xyloglucan (Xyl)-sucrose (Suc) hydrogel was developed for the treatment of deep wounds including pressure ulcers. The dressing was prepared by casing an aqueous solution of Xyl and sugar and then warming, and a hydrogel sheet was obtained. The in vitro characteristics of these sheets, such as their strength, extensibility, water content, adhesion potential, and water absorption, were examined. The strength, Young's modulus, and adhesion strength of the sheets were greater when they had a lower water content. Furthermore, adhesion and gradual water absorbability were similar to those of commercial dressings. These in vitro features suggest that Xyl sheets possess the physicochemical properties required for wound dressings. In the in vivo experiment, a Xyl sheet made from a mixture of 3.0% (w/v) Xyl solution and 33.3% (w/w) Suc, which displayed moderate strength and water content, was selected and compared with gauze, commercial polyurethane film, and Xyl/Suc (1 : 2) hydrogel using a rat deep wound model caused by serious frostbite. Wound healing rates based on reductions in wound areas were the best in the order of the sheet > hydrogel > commercial film > gauze. The sheet resulted in better wound surface states than the other preparations by improving the conditions. Thus, the potential applicability of Xyl sheets to the treatment of deep wounds was demonstrated.

Primary Use of the TruePath Crossing Device for Infrainguinal Chronic Total Occlusions With Intravascular Ultrasound Evaluation.

PURPOSE: To evaluate the use of the TruePath crossing device as the primary recanalization tool for infrainguinal chronic total occlusions (CTO). METHODS: A retrospective analysis was conducted of 50 patients (mean age 75 years; 26 men) with 55 infrainguinal CTOs treated with the TruePath between March 2017 and September 2017 at a single center. The mean occlusion length was 138±55 mm, and femoropopliteal lesions accounted for 65% of the 55 lesions. The primary outcome measure was CTO crossing using the TruePath alone; secondary outcomes were assisted success (>50% lumen gain using the TruePath), device-related complications, and intraluminal crossing evaluated by intravascular ultrasound (IVUS). RESULTS: Complete success was achieved in 33 (60%) of 55 lesions having a mean occlusion length of 145±72 mm. Among these, the true lumen crossing rate was 97% according to IVUS evaluation. Assisted success was achieved in 15 (68%) of the 22 failures. Complete/assisted success, in which the TruePath was thought to have contributed to CTO crossing, was attained in 48 (87%) of the 55 lesions. Three (5.5%) complications were observed: a perforation, an access-site hematoma, and acute occlusion; only the perforation was device related (1.8%). Multivariate analysis showed PACCS grade 4 (odds ratio 4.5, 95% confidence interval 1.33 to 15.5, p=0.02) was an independent predictor of TruePath failure. CONCLUSION: Primary use of the TruePath crossing device for infrainguinal CTOs demonstrated a satisfactory complete success rate and a high rate of IVUS-documented intraluminal crossing with few device-related complications. Severe calcification is an independent predictor of TruePath failure.

Preparation and Evaluation of Stomatitis Film Using Xyloglucan Containing Loperamide.

Stomatitis induced by radiation therapy or cancer chemotherapy is a factor in sleep disorders and/or eating disorders, markedly decreasing patient quality of life. In recent years, disintegrating oral films that are easy to handle have been developed; therefore, we focused on the formulation of these films. We prepared an adhesive film for the oral cavity using xyloglucan (Xylo), which is a water-soluble macromolecule. We used loperamide, which has been reported to relieve pain caused by stomatitis effectively, as a model drug in this study. Films were prepared from Xylo solutions (3% (w/w)) and hypromellose (HPMC) solutions (1% (w/w)). Xylo and HPMC solutions were mixed at ratios of 1 : 1, 2 : 1, or 3 : 1 for each film, and films 2×2 cm weighing 3 g were prepared and dried at 37°C for 24 h. Physicochemical properties such as strength, adhesiveness, disintegration behavior, and dissolution of loperamide from films were evaluated. Films prepared from Xylo solution alone had sufficient strength and mucosal adhesion. On the other hand, films prepared from a mixture of Xylo and HPMC were inferior to those made from Xylo, but showed sufficient strength and mucosal adhesion and were flexible and easy to handle. The films prepared in this study are useful as adhesion films in the oral cavity.

Polymorphisms in base excision repair genes are associated with endometrial cancer risk among postmenopausal Japanese women.

OBJECTIVES: Polymorphisms in base excision repair (BER) genes are associated with risk for several types of cancers but have not been studied with respect to endometrial cancer among Japanese women. Therefore, we conducted a case-control study to explore the association between polymorphisms in BER genes and the risk for endometrial cancer. METHODS/MATERIALS: This study included a total of 91 postmenopausal subjects with endometrial cancer and 261 controls without cancer who visited the Aichi Cancer Center between 2001 and 2005. We focused on single nucleotide polymorphisms within coding regions of 5 BER genes (OGG1, MUTYH, XRCC1, APEX1, and PARP1). To assess lifestyle in the etiology of endometrial cancer, we used a self-administered questionnaire. Associations were evaluated using multivariate unconditional logistic regression models. We also assessed whether there were intergenic associations or an interaction with obesity. RESULTS: We observed a significant association between endometrial cancer risk and XRCC1 rs1799782 (C > T, Arg194Trp) and XRCC1 rs25487 (G > A, Arg399Gln). We uncovered a significant association between obesity (body mass index, ≥ 25) and rs25487. The XRCC1 polymorphisms were in complete linkage disequilibrium, and the XRCC1 haplotype TG associated significantly with endometrial cancer risk. The interaction between the CA haplotype and body mass index was marginally significant, whereas interaction between haplotype in XRCC1 and rs1136410 (PARP1) was not significant. CONCLUSIONS: We found a significant association between endometrial cancer risk and XRCC1 polymorphisms and haplotype TG in postmenopausal Japanese women.

A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population.

Genome-wide association studies (GWASs) have identified genetic variants associated with breast cancer. Most GWASs to date have been conducted in women of European descent, however, and the contribution of these variants as predictors in Japanese women is unknown. Here, we analyzed 23 genetic variants identified in previous GWASs and conducted a case-control study with 697 case subjects and 1,394 age- and menopausal status-matched controls. We fit conditional regression models with genetic variants and conventional risk factors. In addition, we created a polygenetic risk score, using those variants with a statistically significant association with breast cancer risk, and also evaluated the contribution of these genetic predictors using the c statistic. Eleven single-nucleotide polymorphisms (SNPs) revealed significant associations with breast cancer risk. A dose-dependent association was observed between the risk of breast cancer and the genetic risk score, which was an aggregate measure of alleles in seven selected variants, namely FGFR2-rs2981579, TOX3/TNRC9-rs3803662, C6orf97-rs2046210, 8q24-rs13281615, SLC4A7-rs4973768, LSP1-rs38137198, and CASP8-rs10931936. Compared to women with scores of 3 or less, odds ratios (ORs) for women with scores of 4-5, 6-7, 8-9, and 10 or more were 1.33 (95% confidence interval, 1.00-1.80), 1.71 (1.26-2.30), 3.01 (1.97-4.58), and 8.69 (2.75-27.5), respectively (P (trend) = 1.9 × 10(-9)). The c statistic for a model including the genetic risk score in addition to the conventional risk factors was 0.6933, versus 0.6652 with the conventional risk factors only (P = 1.3 × 10(-4)). Population-attributable fraction of the risk score was 33.0%. In conclusion, we identified a genetic risk predictor of breast cancer in a Japanese population. Risk models which include a genetic risk score are possibly useful in distinguishing women at high risk of breast cancer from those at low risk, particularly in the context of targeted prevention.

Variation in M protein production among Streptococcus pyogenes strains according to emm genotype.

M protein is an important virulence determinant in Streptococcus pyogenes, but the amounts of M protein in various strains of the species remain to be elucidated. To assess the amount of M protein in strains of each emm genotype, dot blot analysis was performed on 141 clinically isolated strains. Among the cell membrane-associated proteins, M protein was present in greater quantities in the emm1, 3, and 6 strains than in the other emm strains. In addition three strains, one each of the emm1, 3, and 6 types, showed prolific M protein production (M protein-high producers). These three emm genotypes are frequently isolated in clinical practice. Sequencing of the csrRS gene, one of the two-component signal transduction systems implicated in virulence, was performed on 25 strains bearing different amounts of M protein. CsrS mutations, in contrast to CsrR protein, were detected in 11 strains. The M protein-high producer strain of emm1 type carried two amino acid substitutions, whereas the other three emm1 strains carried only one substitution each. The M protein-high producer expressed its emm gene more strongly than the corresponding M protein-low producer did according to TaqMan RT-PCR. These observations suggest that the accumulation of amino acid substitutions in CsrS protein may contribute, at least in part, to the large amount of M protein production seen in several emm genotypes.

Weight gain during adulthood and body weight at age 20 are associated with the risk of endometrial cancer in Japanese women.

BACKGROUND: Current obesity is an established risk factor for endometrial cancer; however, the roles of weight gain during adulthood and obesity in early adulthood on endometrial cancer have not been elucidated. Here, we conducted a case-control study comprising 222 histologically diagnosed incident endometrial cancer cases and 2162 age- and menstrual-status matched non-cancer controls. METHODS: Information on current body weight, weight and height at age 20 years, and lifestyle/environmental factors was obtained from a self-administered questionnaire. Subjects were classified into 3 groups according to change in body mass index (BMI, kg/m(2)) from age 20 years to enrollment (≤0 [reference], 0-3, and >3 kg/m(2)). The effects of adult BMI change and obesity in early adulthood were evaluated using an unconditional logistic regression model adjusted for potential confounders. RESULTS: A high BMI at age 20 (BMI ≥25, BMI <25 as reference) was significantly positively associated with endometrial cancer risk (P = 0.005), as was a BMI increase during adulthood (0-3 BMI change, multivariate odds ratio [OR] = 1.28, 95% confidence interval [CI] = 0.88-1.87; >3 BMI change, OR = 2.02, 95% CI = 1.38-2.96; P-trend < 0.001). Parity and BMI at age 20 appeared to modify the effect of weight gain on cancer risk, albeit without statistical significance. This positive association of weight gain with risk was observed only for endometrioid adenocarcinoma. CONCLUSIONS: The results show that endometrial cancer is positively associated with obesity at age 20 and weight gain during adulthood among Japanese women.

Association between vitamin D and calcium intake and breast cancer risk according to menopausal status and receptor status in Japan.

Although several studies have investigated the possible association between elevated vitamin D and calcium intake and low breast cancer risk, findings have been inconsistent. We conducted a case-control study to clarify the association between vitamin D and calcium intake and breast cancer risk among pre- and post- menopausal women in Japan. We also investigated whether these effects were modified by tumor receptor status, specifically estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2) status. We examined 1803 breast cancer patients and 3606 age- and menopausal status-matched noncancer controls. Among cases, 713 were assessed for ER, PR, and HER2 status. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional or unconditional logistic models adjusted for potential confounders. A significant inverse association was observed between vitamin D and calcium intake and breast cancer risk among all subjects, with top quartile ORs of 0.76 (95% CI, 0.63-0.90; trend P = 0.001) and 0.83 (95% CI, 0.69-0.99; trend P = 0.038), respectively. In analyses stratified by menopausal status, a significant association between risk and vitamin D was observed only among premenopausal women (trend P < 0.001), whereas that between risk and calcium intake was seen only among postmenopausal women (trend P = 0.022). Heterogeneity by menopausal status for these associations was statistically significant. This association was modified by tumor receptor status. These findings suggest that the protective effects of vitamin D and calcium intake against breast cancer risk may differ by menopausal status and receptor status.

HLA-A alleles and the risk of cervical squamous cell carcinoma in Japanese women.

BACKGROUND: We conducted a case-control study to examine the relationship between human leukocyte antigen-A (HLA-A) allele polymorphism and the pathogenesis of cervical neoplasia among Japanese women. METHODS: A total of 119 patients with invasive cervical squamous cell carcinoma were compared to 119 age- and menopausal status-matched non-cancer controls. Blood samples were taken from all cases and controls and lifestyle information was collected by means of a self-administered questionnaire. The estimated impact of HLA-A alleles on cervical cancer risk was evaluated by unconditional logistic regression models. RESULTS: The frequency of HLA-A(*)0206 among cases was significantly lower than among controls (P = 0.006). There was an inverse association between A(*)0206 and cervical cancer risk (odds ratio [OR] = 0.31, 95% confidence interval [95% CI] = 0.15 to 0.65, P = 0.002), and a positive association for HLA-A(*)2402 (OR = 1.76, 95% CI = 1.00 to 3.09, P = 0.048). After correction for multiple comparisons, A(*)0206 was significantly associated with reduced cervical cancer risk (corrected P = 0.036). Furthermore, the inverse association between A(*)0206 and cervical cancer risk was independent of smoking status (never smoker: OR = 0.37, 95% CI = 0.15 to 0.90; ever smoker: OR = 0.23, 95% CI = 0.06 to 0.89). CONCLUSIONS: There was an inverse association between HLA-A(*)0206 and cervical cancer risk among Japanese women, which suggests that HLA-A polymorphism influences cervical cancer risk. Further investigation in other populations is thus warranted.

Preliminary Investigation of the Usability Characteristics Required for Wound Management Products by Semi-Structural Interview of Medical Staff.

Consideration of drug usability characteristics is important during the design process. Although many wound management products have been developed in recent years, there are few studies on their usability. We investigated the needs and characteristics of wound management products required by medical professionals, so as to consider these in future development projects. Semi-structured interviews were conducted in a group of healthcare professionals. Interview responses were analyzed based on thematic analysis. Four themes common to all facilities were secondary wounds, adaptability of materials, convenience, and physicochemical properties. Economic efficiency of medical care was found to be considered only at the hospital, and quality of life of patients was found to be considered only at the home palliative care clinic. Requirements for wound management products can be affected by participants' roles and their facility settings. However, there were needs common to all fields that all wound management products should aim to incorporate.

Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women.

In postmenopausal women, extraovarian sex hormone production plays an important role in hormone-related diseases, such as breast and endometrial cancers. Aromatase, an enzyme encoded by CYP19A1, is a key enzyme involved in estrogen biosynthesis. The impact of CYP19A1 polymorphisms on serum sex hormone levels in the Japanese population has never been investigated. This study enrolled 100 postmenopausal Japanese women found to be without cancer. Twenty-five CYP19A1 loci were identified, and measurements were conducted on serum levels of sex hormones; lifestyle data were collected, namely estrone (E1), estradiol (E2), testosterone and sex hormone-binding globulin (SHBG). We conducted a cross-sectional analysis to evaluate the impact of CYP19A1 haplotype on serum sex hormone levels. We found that subjects with BMI>or=25 kg/m(2) showed a significant difference in circulating testosterone levels (0.29+/-0.19, P=0.050). Neither age nor the amount of physical exercise or drinking habits showed any effect on hormone levels. We identified seven haplotype blocks in CYP19A1 by LD analysis. Estrone levels differed in rs12148604 (SNP 1) and rs11632903 (SNP14). No significant locus for estradiol was observed. SHBG levels were associated with rs4441215 (SNP11). Testosterone levels were strongly associated with rs752760 (SNP24) and rs2445768 (SNP25) and weakly associated with SNP 1, SNP11 and SNP14 as well. We found that polymorphisms in CYP19A1 influence sex hormone levels in Japanese postmenopausal women.

[Case-surveillance of measles in Aichi Prefecture in 2007].

PURPOSE: Under the Japanese Infectious Disease Prevention Law, measles was monitored by the national epidemiological surveillance system through reports from sentinel clinical institutions until December 2007. In order to obtain rapid and precise information on measles outbreaks and take necessary actions, a case-surveillance system was introduced in Aichi Prefecture in February 2007. In this report, measles cases reported through the case-surveillance system were examined for characteristics of infection and the utility of the system. METHOD: The case-surveillance system for measles started in Aichi in February 2007, all local medical institutions being requested to provide a set of information on every measles case immediately after the clinical diagnosis was made. Reported data were processed by ourselves and real-time surveillance results were shown in our web site. Data were analyzed and compared with measles data from the national epidemiological surveillance system, reported by the sentinel clinical institutions in Aichi. RESULTS: A total of 212 cases were registered through the case-surveillance from February to December 2007, including 123 (58.0%) adult cases (over 15 years old of age). In contrast, only 56 cases were registered in Aichi by the national epidemiological surveillance in 2007 including 11 adult cases (19.6%), indicating considerable under-representation of adult measles cases by the sentinel survey. Of the case-surveillance cases, 56 (26.4%) had an immunization history, 88 (41.5%) were without a history, and 68 (32.1%) were unknown, indicating that primary and/or secondary vaccine failure occurred in at least 26.4%. DISCUSSION: The results of the case-surveillance of measles in Aichi provided useful information on characteristics of measles infection and proved to be effective in detecting the occurrence of measles rapidly and accurately. In order to achieve the Japanese target of measles elimination by 2012, it will be necessary to further strengthen the monitoring system and measures to contain spread of the disease.

Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study.

OBJECTIVE: Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. METHODS: This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. RESULTS: Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). CONCLUSIONS: The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.

BACKGROUND: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. RESULTS: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). CONCLUSIONS: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

One-carbon metabolism-related gene polymorphisms and risk of breast cancer.

Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women.

Effect of soybean on breast cancer according to receptor status: a case-control study in Japan.

The possible association of high soy food consumption with low incidence of breast cancer in Asian countries has been widely investigated, but findings from epidemiologic studies have been inconsistent. Breast cancers defined by receptor status, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) may have distinct etiologic factors. Here, we conducted a case-control study to clarify associations between intake of soybean products and breast cancer risk according to receptor status. A total of 678 breast cancer cases and 3,390 age- and menopausal status-matched noncancer controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders. On analysis according to receptor status, we observed a significantly reduced risk of ER-positive (ER+) (top tertile OR = 0.74; 95% CI, 0.58-0.94; trend p = 0.01) and HER2-negative (HER2-) tumors (top tertile OR = 0.78; 95% CI, 0.61-0.99; trend p = 0.04). Further, when the 3 receptors were jointly examined, a reduced risk was observed only in patients with ER+/PR+/HER2- tumor (top tertile OR = 0.73; 95% CI, 0.54-0.97; trend p = 0.03). These findings indicate that the protective effect of soy against breast cancer risk differs by receptor status.

Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among Japanese.

Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50-1.27) and 0.56 (0.34-0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis.