Ectopic Breast Cancer Arising within an Axillary Lymph Node.

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.

Feedbacks Using behaviOral econOmic theories on STEP countS in Cardiovascular Disease Patients (FOOTSTEPS) Using Novel Daily Step Counts Retrieving System.

The effectiveness of gamification-based feedback systems that utilize non-monetary points to promote exercise among cardiovascular disease (CVD) patients has not been fully evaluated. This study aimed to evaluate the effectiveness of a gamification program using non-monetary points on the daily step counts in CVD patients. We collected 30 patients with a history of heart failure or myocardial infarction at a single tertiary center between January 9, 2023, and April 13, 2023. The primary outcome was the change in daily step counts. The baseline step counts were compared with those during the 4-week gamification and the 1-week follow-up period. A total of 29 participants with a mean age of 64.6 years were finally enrolled, and 8 (27.6%) were female. Among them, 23 (79.3%) had a history of old myocardial infarction, and 9 (31.0%) had a history of chronic heart failure. During the intervention period, the average daily step counts increased significantly from baseline in weeks 1-5 (week 1: 1165 steps; 95% CI, 319-2011; P = 0.009, week 2: 1508; 635-2382; P = 0.001, week 3: 1321; 646-1996; P < 0.001, week 4: 1436; 791-2081; P < 0.001, week 5:1148; 436-1860; P < 0.001). Higher body mass index was statistically associated with the smaller difference in step counts from the baseline, and the lower proportion of achievement of step count goals. Female sex was significantly associated with the higher proportion of achievement of step count goals. In conclusion, this pilot prospective interventional study demonstrated the effectiveness of gamification-based feedback systems that utilize non-monetary points to increase daily step counts in CVD patients.

Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

OBJECTIVES: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. METHODS: The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. RESULTS: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. CONCLUSIONS: This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

The effectiveness of controlled ovarian stimulation with tamoxifen for patients with estrogen-sensitive breast cancer: A systematic review and meta-analysis.

Purpose: Tamoxifen is used for the suppression of estrogen-sensitive tumor recurrence in oocyte retrieval cycles. This meta-analysis aimed to evaluate the quality of controlled ovarian stimulation (COS) with co-administration of gonadotropins and tamoxifen (COS with tamoxifen). Methods: PubMed, Embase, and Cochrane Library were searched for articles on October 30, 2022. The authors included studies comparing COS with tamoxifen and COS with gonadotropins and letrozole (COS with letrozole) or gonadotropin only (COS with gonadotropin only) for fertility preservation in patients with breast cancer. The main outcome measures were the COS quality, total number of retrieved oocytes (TOR), total number of mature oocytes (TMO), and peak estradiol levels (PEL). Results: Four studies (348 patients, two randomized controlled trials, and two cohort studies) were included in our meta-analysis. There was no significant difference in TOR (95% CI, [-3.84, 2.90]) and TMO (95% CI, [-2.20, 2.64]) between COS with tamoxifen and COS with letrozole. There was also no difference in TOR (95% CI, [-6.14, 1.86]) between COS with tamoxifen and COS with gonadotropin only. Statistically significant decrease was observed in PEL during COS with letrozole compared with tamoxifen (95% CI, [1414.4, 4953.7]). Conclusions: The quality did not differ between COS with tamoxifen and COS with letrozole or gonadotropin only.

Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Useful manifestations to detect adenovirus in children with upper respiratory infections: A retrospective study.

OBJECTIVE: Approximately 1 million adenovirus immunochromatography (IC) kits are annually used in Japan. However, no practical strategies have been developed regarding their use for detecting adenovirus. The present study aims to verify the usefulness of clinical manifestations in making decisions regarding the use of adenovirus IC kits for children with upper respiratory infections (URI). METHODS: The medical records of 825 pediatric cases tested by IC kits for adenovirus were extracted from clinical laboratory department database over a 3-year period at our hospital. Among them, 585 patients were suspected adenovirus URI, and their clinical manifestations were reviewed. After data cleaning, 10 types of clinical manifestations were statistically analyzed between adenovirus IC kit-positive and -negative groups. Multivariate analysis was performed to select significant clinical manifestations using adenovirus IC kit positivity as the objective variable. RESULTS: Among 585 pediatric patients, the cases of 420 patients, with suitable data for whom no other pathogen was detected, were reviewed. Adenovirus was detected in 86 cases. Multivariate analysis identified a significant difference for three clinical manifestations: (1) fever ≥ 39.0°C, (2) rhinorrhea, and (3) tonsillar exudate. The negativity rate for the IC kit was 90% when none of the three manifestations was observed. CONCLUSIONS: The results suggested that IC kits for adenovirus tend to give negative results in cases that lack all the three above mentioned clinical manifestations.

Chondroitin Sulfate N-acetylgalactosaminyltransferase-2 Impacts Foam Cell Formation and Atherosclerosis by Altering Macrophage Glycosaminoglycan Chain.

OBJECTIVE: Chondroitin sulfate proteoglycans are the primary constituents of the macrophage glycosaminoglycan and extracellular microenvironment. To examine their potential role in atherogenesis, we investigated the biological importance of one of the chondroitin sulfate glycosaminoglycan biosynthesis gene, ChGn-2 (chondroitin sulfate N-acetylgalactosaminyltransferase-2), in macrophage foam cell formation. Approach and Results: ChGn-2-deficient mice showed decreased and shortened glycosaminoglycans. ChGn-2-/-/LDLr-/- (low-density lipoprotein receptor) mice generated less atherosclerotic plaque after being fed with Western diet despite exhibiting a metabolic phenotype similar to that of the ChGn-2+/+/LDLr-/- littermates. We demonstrated that in macrophages, ChGn-2 expression was upregulated in the presence of oxLDL (oxidized LDL), and glycosaminoglycan was substantially increased. Foam cell formation was significantly altered by ChGn-2 in both mouse peritoneal macrophages and the RAW264.7 macrophage cell line. Mechanistically, ChGn-2 enhanced oxLDL binding on the cell surface, and as a consequence, CD36-an important macrophage membrane scavenger receptor-was differentially regulated. CONCLUSIONS: ChGn-2 alteration on macrophages conceivably influences LDL accumulation and subsequently accelerates plaque formation. These results collectively suggest that ChGn-2 is a novel therapeutic target amenable to clinical translation in the future. Graphic Abstract: A graphic abstract is available for this article.

The loss of endothelin-2 exhibits an anticancer effect in A549 human lung adenocarcinoma cell line.

Lung cancer is the leading cause of cancer-related deaths worldwide, and adenocarcinoma is the most common subtype of lung cancer. Endothelin-2 (ET-2) is expressed in the epithelium of alveoli, and its expression is increased in cancer. However, the role of ET-2 in lung adenocarcinoma remains unclear. This study aimed to investigate the pathophysiological functions of ET-2 in A549 human lung adenocarcinoma cells. We analyzed the expression of ET-2 mRNA in lung adenocarcinoma tissues compared with that in nontumor lung tissues using public online databases. The function of ET-2 in A549 cells was investigated using siRNA. ET-2 mRNA level was upregulated in lung adenocarcinoma tissues, and high ET-2 level was associated with poor overall survival in patients with lung adenocarcinoma. ET-2 silencing reduced the proliferation, migration, and invasion, and enhanced apoptosis in A549 cells. Mechanistically, ET-2 silencing reduced the expression levels of X-linked inhibitor of apoptosis and survivin, which are members of the inhibitor apoptosis protein family. In addition, silencing ET-2 inhibited epithelial-mesenchymal transition, which halted migration. Therefore, the specific targeting of ET-2 may be a potential treatment strategy for lung adenocarcinoma.

Distinct effects of orexin receptor antagonist and GABAA agonist on sleep and physical/cognitive functions after forced awakening.

The majority of patients with insomnia are treated with hypnotic agents. In the present study, we evaluated the side-effect profile of an orexin receptor antagonist and γ-aminobutyric acid A (GABAA) receptor agonist on physical/cognitive functions upon forced awakening. This double-blind, randomized, placebo-controlled, cross-over study was conducted on 30 healthy male subjects. Fifteen minutes before bedtime, the subjects took a pill of suvorexant (20 mg), brotizolam (0.25 mg), or placebo and were forced awake 90 min thereafter. Physical- and cognitive-function tests were performed before taking the pill, after forced awakening, and the next morning. Polysomnographic recordings revealed that the efficacies of the hypnotic agents in prolonging total sleep time (∼30 min) and increasing sleep efficiency (∼6%) were comparable. When the subjects were allowed to go back to sleep after the forced awakening, the sleep latency was shorter under the influence of hypnotic agents (∼2 min) compared to the placebo trial (24 min), and the rapid eye movement latency was significantly shorter under suvorexant (98.8, 81.7, and 48.8 min for placebo, brotizolam, and suvorexant, respectively). Although brotizolam significantly impaired the overall physical/cognitive performance (sum of z score) compared with placebo upon forced awakening, there was no significant difference in the total z score of performance between suvorexant and placebo. Notably, the score for static balance with the eyes open was higher under suvorexant compared to brotizolam administration. The energy expenditure was lower under suvorexant and brotizolam compared with the placebo. The effect size of brotizolam (d = 0.24) to reduce the energy expenditure was larger than that of suvorexant (d < 0.01).

Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments.

PURPOSE: Epidemiological studies have suggested that intake of soy isoflavones is associated with a reduced risk of development of breast cancer and an improved prognosis in patients with breast cancer. In addition, basic research has demonstrated the antitumor effects of these compounds on breast cancer cell lines. However, the detailed effects of the intake of equol, which is one of the metabolites of the soy isoflavones, are yet to be clarified on the risk of development and recurrence of breast cancer and its interactions with drugs used for treating breast cancer. This study aimed to determine the antitumor effects of equol and investigate the impact of adding equol to therapeutic agents for breast cancer using breast cancer cell lines. METHODS: We examined the antitumor effect of equol on breast cancer cell lines using MTS assay. We also studied the combined effect of equol and the existing hormonal or chemotherapeutic agents using combination index. We evaluated the expressions of the related proteins by Western blot analysis and correlated the findings with the antitumor effect. RESULTS: Equol showed bi-phasic protumor and antitumor effects; at a low concentration, it promoted the tumor growth in hormone receptor-positive cell lines, whereas antitumor effects were generally observed when an excessive amount of dose unexpected in the blood and the tissue was administered. When used with tamoxifen, equol might have some antagonistic effect, although it depends on equol concentration and the type of cancer cells. CONCLUSIONS: We confirmed that equol has dual action, specifically a tumor growth-promoting effect and an antitumor effect. Although the results suggested that equol might exert an antagonistic effect against tamoxifen depending on the concentration, equol did not exert an antagonistic effect on other therapeutic agents.