The prevalence of osteoporosis has increased in super-aging societies. To prevent subsequent fractures from occurring after initial osteoporotic fracture, coordinator-based systems called fracture liaison service (FLS) have been implemented worldwide. In Japan, the osteoporosis liaison service (OLS) including FLS was launched in 2011 in order to reduce the incidence of both primary and secondary fractures in osteoporosis patients. Multidisciplinary management by an OLS coordinator aims to support patient care, monitor medicine adherence, and improve quality of life of the elderly. A framework such as OLS-7 has been proposed to provide comprehensive support regardless of the expertise of each medical staff.

Decidualization is a process of differentiation of human endometrial stromal cells (hESCs) accompanied by dramatic changes in cellular functions. This process is critical for embryo implantation and the establishment of pregnancy. Impairment of decidualization of hESCs leads to implantation failure, miscarriage, and unexplained infertility. The present review focuses on the metabolic changes in hESCs during decidualization. One of the changes taking place is in the glucose metabolism. Glucose uptake increases during decidualization because glucose is essential for the decidualization of hESCs. In hESCs, GLUT1 is highly expressed and involved in the increase of glucose uptake during decidualization. The up-regulation of GLUT1 is mediated by an epigenetic mechanism, which is regulated by CCAAT enhancer-binding protein β (C/EBPβ) and Wilms tumor 1 (WT1). Another metabolic change is in the lipid metabolism. Lipid accumulation in hESCs increases during decidualization. This increase is mediated by very low-density lipoprotein receptor (VLDLR). The up-regulation of VLDLR is regulated by WT1. In contrast to glucose, lipid is not essential for decidualization of hESCs. Endometrial cells have been implicated as important sources of nutrition for the embryo. hESCs may increase glucose and lipid storage so that they can supply them to the embryo during the implantation process. Taken together, decidualization is the process accompanied by metabolic changes, which may be associated with successful implantation.

Few studies have considered the effect of statins on bone turnover biomarker levels and the results of these studies are inconsistent. Here we performed a meta-analysis of the effect of statins on bone turnover biomarker levels. We used keywords, free words, and related words that included the terms “hydroxymethylglutaryl-CoA reductase inhibitors,” “statin,” and “bone turnover biomarkers” to search PubMed, Cochrane Library, and Embase. The Cochrane Risk Bias Evaluation Tool was used to evaluate the risk of bias, and Review Manager 5.3 and Stata 13.0 were used for statistical analyses. Six randomized controlled trials involving a total of 382 subjects were included in the meta-analysis. The results showed that statins increased the osteocalcin (OC) [mean difference (MD) = 0.73 ng/mL, 95% CI: 0.12, 1.35, I² = 23% and p = 0.26], and decreased cross-linked N-telopeptide (NTX) (MD = –1.14 nM BCE, 95% CI: –2.21, –0.07, I² = 0%, p = 0.53) and C-terminal peptide of type I collagen (CTX) (MD = –0.03 ng/mL, 95% CI: –0.05, –0.01, I² = 0% and p = 0.56). There was no effect on bone-specific alkaline phosphatase (MD = –1.37 U/L, 95% CI: –3.09, 0.34, I² = 0% and p = 0.94) and intact parathyroid hormone (MD = –1.73 pg/mL, 95% CI: –4.35, 0.89, I² = 0% and p = 0.77). Statins increase bone formation biomarker OC and decrease bone resorption biomarker NTX and CTX levels.

To establish a nomogram for predicting large-number cervical lymph node metastases (LNMs) of primary papillary thyroid carcinoma (PTC) based on ultrasound characteristics. This retrospective study included patients with PTC diagnosed by pathological examination and who underwent surgery between August 2015 and May 2021 at Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo, China). Large-number LNM was defined as >5 lymph nodes with metastases. The patients were propensity score-matched (PSM) for age and sex. A multivariable analysis was used to determine the risk factors for massive LNM. After PSM, the 78 patients with large-number LNM were matched with 312 patients with small-number LNM. Compared with the patients with small-number LNM, those with large-number LNM had larger tumors (13.0 ± 7.7 vs. 6.8 ± 3.8 mm, p < 0.001), and higher frequencies of multifocal nodules (42.3% vs. 22.4%, p < 0.001), taller-than-wide shape (82.1% vs. 56.7%, p < 0.001), calcifications (76.9% vs. 47.4%, p < 0.001), microcalcifications (68.0% vs. 36.5%, p < 0.001), capsule invasion (32.1% vs. 17.6%, p = 0.005), and ultrasound diagnosis of LNM (44.9% vs. 9.3%, p < 0.001). The multivariable analysis showed that nodule size (OR = 1.19, 95%CI: 1.11–1.27, p < 0.001), multifocal disease (OR = 2.50, 95%CI: 1.30–4.80, p = 0.006), taller-than-wide shape (OR = 0.45, 95%CI: 0.22–0.93, p = 0.032), and ultrasound diagnosis of LNM (OR = 5.57, 95%CI: 2.73–11.37, p < 0.001) were independently associated with large-number LNM. A nomogram was built, and the area under the receiver operating characteristics curve was 0.86 (95%CI: 0.81–0.90). A nomogram was successfully built to predict large-number LNM in patients with PTC, based on nodule size, multifocality, taller-than-wide shape, and ultrasound diagnosis of LNM.

In Japan, the standard method for measuring plasma aldosterone concentration (PAC) for primary aldosteronism (PA) diagnosis was changed from radioimmunoassay (RIA) to a novel chemiluminescent enzyme immunoassay (CLEIA). The purpose of this study is to simulate the possible impact of the change on PA diagnosis. This retrospective study assessed 2,289 PA patients. PACs measured by conventional RIA were transformed to estimated PACs (CLEIA) as follows: RIA (pg/mL) = 1.174 × CLEIA (pg/mL) + 42.3. We applied the estimated PAC (CLEIA) to the conventional cut-off of aldosterone-to-renin activity ratio ≥200 for screening and captopril challenge test (CCT) and PAC ≥60 pg/mL for saline infusion test (SIT). Application of the estimated PAC to screening and confirmatory tests decreased the number of PA diagnoses by 36% (743/2,065) on CCT and 52% (578/1,104) on SIT (discrepant cases). Among the discrepant cases, 87% (548/628) of CCT and 87% (452/522) of SIT were bilateral on adrenal venous sampling (AVS). Surgically treatable aldosterone-producing adenomas (APAs) were observed in 6% (36/579) and 5% (23/472) of discrepant cases on CCT and SIT, respectively; most were characterized by hypokalemia and/or adrenal nodule on CT imaging. Application of the PAC measured by the novel CLEIA to conventional cut-offs decreases the number of PA diagnoses. Although most discrepant cases were bilateral on AVS, there are some APA cases that were characterized by hypokalemia and/or adrenal tumor on CT. Further studies which evaluate PACs measured by both RIA and CLEIA for each patient are needed to identify new cut-offs for PAC measured by CLEIA.

The earlier initiation of growth hormone (GH) treatment for patients with Prader-Willi syndrome (PWS) who are younger than 2 years has become more prevalent. Because free thyroxine (FT4) levels are low during this period, GH may induce further reductions; however, limited information is currently available on this issue. Therefore, we herein performed age-dependent and time-course analyses of thyroid hormone levels in GH-treated PWS children. This retrospective analysis included genetically diagnosed PWS patients (N = 37, median age of 26 months). An age-dependent analysis was performed by subdividing subjects based on age [a younger group aged between 1 and 24 months (N = 16) and an older group between 25 and 84 months (N = 21)] and was followed by a multiple regression analysis with adjustments for sex and the cumulative GH dose per bodyweight. A time-course analysis of subjects who had not received levothyroxine during the first 18 months of GH treatment (N = 28) was conducted. A one-month treatment with GH decreased FT4 levels in the older group, but not in the younger group, and this was associated with increases in thyroid-stimulating hormone levels. A positive correlation was noted between age and decreases in FT4 levels independent of the cumulative GH dose per bodyweight. The time-course analysis revealed no changes in FT4 levels in the younger group, while transient decreases were observed in the older group. In conclusion, GH treatment causes age-dependent changes in FT4 levels. This result will help clinicians establish a therapeutic strategy to decide the necessity of levothyroxine supplementation in GH-treated children with PWS.

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.

Prader-Willi syndrome (PWS) is a multisystem disorder with increased mortality predominantly due to obesity-associated complications; therefore, the management of obesity has been centric to therapeutic strategies for PWS. Although a multidisciplinary team approach has been successful for this purpose during childhood, it is generally difficult to implement during adulthood because of the lack of a structured transitional care program. A more detailed understanding of the current medical conditions of adults with PWS is needed to establish this program; however, limited information is currently available on this issue in Japan. Accordingly, we performed a questionnaire-based survey on 425 patients with PWS. There were 162 adult patients aged 18 years or older with median body mass indexes (kg/m²) of 29.4 and 30.4 in males and females, respectively. The frequencies of type 2 diabetes mellitus (T2DM) and hypertension in adults with PWS were 40.4 and 19.4%, respectively. Growth hormone (GH) therapy during childhood correlated with lower rates of T2DM and hypertension during adulthood. Among adult patients, 54% were treated by pediatricians, whereas 44% were seen by internists with an endocrinologist/diabetologist being the most prevalent. Adult patients treated with GH during childhood showed a higher rate of being seen by pediatricians than those without, demonstrating that the multidisciplinary team approach, typically applied with GH therapy, may be continuously provided even after they reach adulthood. These results emphasize the importance of the seamless provision of the multidisciplinary team approach, which is of clinical importance for establishing an optimal transitional care program for PWS.

The NOD-like receptor protein 3 (NLRP3) inflammasome plays a key role in lipid metabolism. We used an oral fat tolerance test (OFTT) to detect whether serum NLRP3 levels differed in people with different fat tolerances and evaluate whether NLRP3 was associated with impaired fat tolerance (IFT) and hypertriglyceridemia (HTG). We performed the OFTT using 176 volunteers. The groups were divided according to fasting and postprandial triglyceride (TG) levels: 1) normal fat tolerance (NFT) group (TG at 0 h <1.7 mmol/L and TG at any time point <2.5 mmol/L); 2) IFT group (TG at 0 h <1.7 mmol/L and TG at any time point >2.5 mmol/L); and 3) HTG group (TG at 0 h ≥1.7 mmol/L). With decreased lipid tolerance, the TG and NLRP3 levels increased gradually before a high-fat meal and at any time point after 0 h. NLRP3 levels reached a peak 2 h after meal consumption in all three groups. After adjustment for confounding indicators, logistic regression analysis revealed that fasting serum NLRP3 levels were positively associated with both IFT and HTG (for IFT, odds ratio [OR]: 1.079 [1.037–1.123], p < 0.001; for HTG, OR: 1.085 [1.049–1.123], p < 0.001). According to the receiver operating characteristic curve, fasting serum NLRP3 levels were an effective biomarker for IFT and HTG diagnosis. These results indicate that the fasting serum NLRP3 is an independent risk factor for IFT and HTG, and is a valuable indicator for the early diagnosis of IFT and HTG.

The effect of potassium iodide (KI) on radioiodine uptake (RAIU) before radioisotope therapy in Graves’ disease (GD) patients was investigated. A total of 82 patients who had been treated with KI monotherapy before 24-hour RAIU (24 h RAIU) were evaluated and 354 of those who had been treated with thiamazole (MMI) monotherapy were extracted from the 1,130 GD patients who were identified as having had appropriate iodine restriction based on urinary iodine excretion. Urinary iodine excretion (UIE) <200 μg/day was confirmed in all subjects. Propensity score-matching was performed to identify the difference in 24 h RAIU between the KI group and the MMI group. In addition, multiple regression analysis was performed to evaluate related to 24 h RAIU. Propensity score-matching resulted in 57 matched patients in each group. After matching, 24 h RAIU was still significantly lower in the KI group than in the MMI group (median 53% (interquartile range 47–61%) vs. 63% (56–66%); p = 0.001). In addition, KI monotherapy was weakly negatively correlated with 24 h RAIU, whereas the female sex and FT3 were very weakly positively correlated on multiple regression analysis. The results suggest that KI monotherapy likely suppressed 24 h RAIU more than MMI monotherapy in GD patients with appropriate iodine restriction, given the difference in the mechanism of hormone suppression.