Sasaki Institute

Osteoporosis causes fractures which further increase the disease burden of rheumatoid arthritis (RA), however, osteoporosis treatment rates remain low. While several studies have reported that biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) can prevent or improve osteoporosis in RA, our large-scale, real-world study showed that 1 year-b/tsDMARDs use did not arrest osteoporosis progression. This study aimed to examine longer-term changes in bone mineral density (BMD). BMD was observed for up to 5 years in patients receiving b/tsDMARDs for active RA. The primary endpoint was change in BMD (T-score), and the secondary endpoint was change in T-score-related factors. In total, 797 patients (anti-osteoporosis (-), n = 645; anti-osteoporosis (+), n = 152) were included, with a median 3.1-year follow-up (2,489 patient-years). Clinical disease activity index (CDAI) improved in both groups (26.0/24.4 → 6.6/6.8). T-scores decreased significantly in the femoral neck and radius in the anti-osteoporosis (-) group but not in the anti-osteoporosis (+) group [anti-osteoporosis (-): mean change -0.11/-0.33, both p < 0.001; anti-osteoporosis (+):-0.01/-0.10, p = 0.830/0.071]. Overall, 460 patients (58%) experienced a decrease in T-score. A high baseline T-score correlated with a subsequent decrease, while longer osteoporosis treatment duration correlated with an increase. Unexpectedly, the duration of b/tsDMARD use and mean CDAI during observation were not associated with BMD maintenance. Even when RA activity was controlled with b/tsDMARDs, BMD still decreased. This study emphasizes the importance of considering osteoporosis as an independent aspect of RA, beyond inflammation control.

Humoral factors regulating cardiac myocytes have not yet been fully elucidated. Using mass spectrometry, we analyzed peptides released from primary neonatal rat cardiac fibroblasts to identify a 24-amino-acid peptide with an intramolecular disulfide bond. It is derived from the C-terminal end of integral membrane protein 2A (ITM2A), a single-pass type II membrane protein; the peptide sequence is identical between humans and rodents and N-terminally flanked by conserved dibasic residues KR. The ITM2A peptide stimulated secretion of atrial natriuretic peptide (ANP), the predominant hormone produced by cardiac myocytes, in a Langendorff rat heart perfusion system as well as a primary culture of neonatal rat ventricular myocytes. These ANP secretion changes were not accompanied by an alteration in the beating rate, a key determinant of ANP secretion. In a mouse cardiac infarction model, both plasma ANP concentration and ITM2A gene expression in heart tissue reached a peak level on day 7 after operation. Our findings provide new insight into cardiac cell-to-cell communication that regulates ANP secretion.

Long-term health outcomes in living kidney donors (LKDs) are generally favourable. However, recent studies suggest a slightly increased malignancy risk when compared to the general healthy population. Malignancies are influenced by environmental and racial factors; nonetheless, descriptive epidemiological studies on malignancy incidence in LKDs in Asia are lacking. In this study, we aimed to investigate the incidence and characteristics of post-donation malignancies in LKDs. This retrospective observational study included 196 LKDs who underwent nephrectomies between 2008 and 2023. LKDs were categorised into new-onset malignancy and non-malignancy cohorts. Postoperative malignancy surveillance combined population-based cancer screenings, employer-sponsored health examinations, self-paid health checkups, and active surveillance. Baseline characteristics, cancer types, outcomes, and the correlation between cancer incidence and postoperative albuminuria were analysed. Eighteen LKDs (9.2%) developed malignancies over a mean follow-up of 6.7 ± 4.1 years, with an incidence rate of 13.6 per 1000 person-years. The most common cancers were gastric, colorectal, and prostate. Malignancy was more frequent in older donors, males, and those with postoperative hypertension. Most cases were detected at an early stage, allowing curative treatment. The most common diagnostic category of cancer identified was performed as part of our institution's active surveillance. No notable correlation was observed between albuminuria and cancer incidence. While some LKDs developed post-donation malignancies, appropriate and balanced cancer surveillance is essential in managing LKDs, in whom the principle of "do no harm" must be upheld. Establishing a structured system, including public screening programmes and LKD-specific surveillance, would help ensure donor safety and long-term health.

BackgroundGastrointestinal neuroendocrine tumors (GI-NETs) are slow-growing tumors with the potential for malignancy that originate from neuroendocrine cells. Therefore, early diagnosis and treatment of GI-NETs are necessary to prevent metastasis. The widespread use of colonoscopy, which allows early detection of rectal neuroendocrine tumors (rNETs) that are small enough to be treated endoscopically, has resulted in an increasing rate of endoscopic resection of rNETs. However, whether the long-term prognosis of endoscopically resected rNETs is favorable has not yet been determined. This study aimed to assess whether endoscopically resected rNETs affect the long-term prognosis of patients.MethodsWe retrospectively reviewed the medical records of 163 consecutive patients with rNETs who underwent endoscopic resection at 11 hospitals in Japan between 1999 and 2012. The primary analysis focused on 47 patients with 51 rNETs who underwent ≥ 10 years of follow-up. The secondary analysis focused on patients who underwent less than 10 years of follow-up.ResultsThe median follow-up period of patients included in the primary analysis was 12.3 years (range, 10–19.1 years). The median lesion size was 5 mm (range, 2–12). Three lesions were treated using conventional endoscopic mucosal resection (EMR). Twenty-nine lesions were treated using modified EMR. Nineteen lesions were treated using endoscopic submucosal dissection. The R1 resection rate and lymphovascular invasion rate were 15.7% and 25.5%, respectively. The curative resection (CR) rate and non-CR rate were 66.7% and 33.3%, respectively. Two patients with lesions treated with non-CR underwent radical surgery. None of the 47 patients experienced lesion recurrence during the 10-year follow-up period. Two patients whose lesions were treated with CR died of other diseases.ConclusionsDeath attributable to rNETs did not occur among patients who underwent at least 10 years of follow-up after endoscopic resection.

Dietary habits may impact the prevention and management of schizophrenia (SCZ) and bipolar disorder (BD), and genetic and environmental factors can influence both these habits and these disorders. This study investigated the effects of genetic predispositions to SCZ and BD on current dietary habits among older adults with lifestyle-related diseases, potentially offering insights for preventive mental health strategies. A cohort of 730 older patients who were diagnosed with or suspected of having lifestyle-related diseases was assessed for eight current dietary categories: miso soup, Japanese tea, green and yellow vegetables, light-colored vegetables, fruits, pickles, meats, and soybeans. Polygenic risk scores (PRSs) for the risk of SCZ and BD, including BD types I and II, the shared risk of SCZ and BD, and the differentiation of SCZ from BD, were calculated utilizing data from large-scale genome-wide association studies (GWASs). Our findings revealed that PRSs for SCZ and BD risk significantly influenced specific dietary habits, particularly decreased consumption of nutrient-rich foods such as light-colored vegetables (SCZ, R2 = 0.0096, p = 3.54 × 10−3; BD, R2 = 0.0074, p = 9.09 × 10−3) and soybeans (SCZ, R2 = 0.0061, p = 0.019; BD, R2 = 0.014, p = 8.38 × 10−4). Notable differences in dietary effects were observed between PRSs for BD I and BD II, with a more pronounced impact associated with BD I (e.g., light-colored vegetables, BD I, R2 = 0.015, p = 3.11 × 10−4; BD II, p > 0.05). Moreover, shared genetic factors for SCZ and BD were correlated with lower intakes of miso soup (R2 = 0.013, p = 1.21 × 10−3), Japanese tea (R2 = 0.0092, p = 5.59 × 10−3), light-colored vegetables (R2 = 0.010, p = 2.92 × 10−3), and soybeans (R2 = 0.014, p = 3.13 × 10−4). No significant correlations were found between PRSs for differentiating SCZ from BD and any dietary patterns (p > 6.25 × 10−3). Genetic risks shared by individuals with SCZ and BD may influence dietary choices in older adults, emphasizing the potential for dietary modifications as part of comprehensive strategies for the prevention of the SCZ and BD onset, as well as for the treatment of individuals at risk of or diagnosed with SCZ and BD.

The International Commission on Radiological Protection (ICRP) started to prepare the new general recommendations. The Fukushima Daiichi Nuclear Power Plant accident in March 2011 which followed the Great East Japan Earthquake and a gigantic Tsunami was the first large nuclear accident since ICRP 2007 Recommendations became effective. The experiences and notions of the accidents, countermeasures, and restorations are expected to contribute to the production of the new general recommendations. The author served as a member of the main commission (MC) of ICRP from July 2001 to June 2009 and participated in nearly the whole process of producing ICRP 2007 Recommendations. This article reminisces about the works in which the MC had engaged during that period. The author expects the story which includes personal impressions may serve as useful information for those who are involved in preparation of the new recommendations, from Japan in particular. This article is based on an invited lecture which was presented at the 56th Congress of the Japan Health Physics Society held jointly with the 7th International Symposium on the System of Radiological Protection (ICRP 2023) in Tokyo.