Targeted metabolomic analysis of early-trimester serum identifies potential mechanisms for late-onset preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder. Late-onset (Lo)-PE can cause serious complications in both the mother and child. This study aimed to explore biomarkers for elucidating the mechanisms underlying Lo-PE, via a metabolomic analysis of first-trimester maternal serum. METHODS: This study was conducted at Fukushima Regional Center as an adjunct to Japan Environment and Children Study and included 12 patients with Lo-PE matched to 12 women with healthy pregnancies. Capillary electrophoresis-mass spectrometry-based quantitative analyses of charged metabolites were performed on first-trimester maternal serum samples. RESULTS: Overall, 183 charged metabolites were identified. The peak area of glucosamine was significantly higher for the first-trimester sera of patients with Lo-PE than that for controls. Conversely, the peak area of serotonin was significantly decreased in the sera of patients with Lo-PE. CONCLUSIONS: During early pregnancy, glucosamine and serotonin levels in maternal serum may serve as early biomarkers for Lo-PE. As part of preconception care, pre-pregnancy dietary habits and mental health could potentially prevent Lo-PE onset.

Lepidic Pulmonary Metastasis from Pancreatic Carcinoma Mimicking Organizing Pneumonia, Diagnosed by a Transbronchial Cryobiopsy.

A 78-year-old man with a history of pancreatic carcinoma underwent chest computed tomography (CT), which revealed a slowly enlarging consolidation in the right lower lobe. Forceps and percutaneous CT-guided lung biopsies showed no evidence of malignancy; therefore, organizing pneumonia was suspected. However, the patient's serum carbohydrate antigen 19-9 levels increased monthly, raising concerns about malignant lesions. A transbronchial cryobiopsy (TBCB) was performed to confirm the diagnosis of pulmonary metastasis of the pancreatic carcinoma. Pulmonary metastasis is an important differential diagnosis when chest CT shows consolidation, mimicking organized pneumonia. In addition, a TBCB can be a useful diagnostic tool for detecting lepidic growth patterns.

Improvement of social frailty is associated with stability of nonparametric characteristics of the rest-activity rhythm and improvement of the usual walking ability in the elderly.

Our study, conducted between April 2022 and January 2024, was aimed at clarifying components of the rest-activity rhythm (RAR) involved in improvement of social frailty state before or after a 3-month multi-component exercise intervention in the elderly. Participants were recruited from the general population in Akita prefecture, Japan. We administered a four-item social frailty screening questionnaire to classify the severity of social frailty in each participant before and after the 3-month intervention. The RAR parameters were measured on an Actiwatch Spectrum Plus device worn by the subjects for 7 continuous days. As the final sample, 65 participants classified into the improved/maintained group (n = 36) or the deteriorated group (n = 29) according to the change in the social frailty classification after the intervention were included in the analysis. The results of a binomial logistic regression analysis showed significantly higher values of interdaily stability (IS) and usual walking speed at the post-test after the intervention. Based on our findings, we propose that stability of the rest-activity rhythm related to synchronization with external stimuli (such as social effect and physical activity) might have clinical impact on improvement of social frailty state in elderly community-dwellers.

Successful treatment of type B2 thymoma with steroid and radiotherapy.

An 86-year-old woman with leg edema and dyspnea on exertion was admitted to our hospital. Chest computed tomography (CT) revealed a mass in the anterior mediastinum with pericardial invasion. Histological examination with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) led to the diagnosis of Masaoka stage IVa type B2 thymoma. For palliation, radiotherapy (32 Gy/16 fractions) and prednisolone (30 mg/day) were administered and tapered. After treatment, both the pericardial effusion and tumour size decreased. Combination therapy with steroids and radiotherapy may be effective for treating thymomas.

An academic cooperation between the Japan Sports Nutrition Association (JSNA) and the Korean Society for Exercise Nutrition (KSEN).

PURPOSE: The Japan Sports Nutrition Association (JSNA) is an academic society that aims to contribute to people's health and the development of sports in Japan. METHODS: After numerous communication and academic events, the JSNA and the Korean Society for Exercise Nutrition (KSEN) exchanged a Memorandum of Understanding (MoU) in 2018. RESULTS: Based on the MoU, the JSNA and KSEN organized academic exchange events until the Coronavirus Disease 2019 pandemic and subsequent travel restrictions and lockdowns. CONCLUSION: After four years of the pandemic and the downgrading of Coronavirus Disease 2019 infection risk, it is hoped that academic exchanges between the societies will resume gradually and enhance members' recognition of the cooperation between the JSNA and KSEN for active collaborations in the future.

Relationship between sleep position and otitis media in infants: The Japan environment and children's study.

OBJECTIVE: Otitis media is a disease that commonly occurs in infants. Various risk factors have been reported. Sleep position has been reported to be associated with various diseases. There is no report on the relationship between otitis media and sleep position. We examined the incidence of otitis media and sleep position in infants. METHODS: We used data from the Japan Environment Children's Study. We used multivariate logistic analysis to examine the relationship between sleep position and the incidence of otitis media in infants aged up to 6 months. In addition, we conducted a stratified analysis based on whether the child was able to turn over in bed at 6 months of age. RESULTS: The study population comprised 85,731 participants. The incidence of otitis media by sleep position was significantly higher when the infant was in the prone position compared to any other position (adjusted odds ratio, 1.206; 95 %CI, 1.038-1.401). Stratified analysis of turning showed that otitis media was more common in the prone position in all groups. CONCLUSION: In the current study, infants aged 6 months or younger who slept in the prone position were more likely to have otitis media. Sleep position interview and guidance on changing sleep position may be useful for the prevention of otitis media.

Association Between Atopic Dermatitis in Pregnant Women and Preterm Births: The Japan Environment and Children's Study.

OBJECTIVES: This study aimed to evaluate the association between atopic dermatitis in pregnant women and preterm births, accounting for maternal ritodrine hydrochloride administration status. METHODS: Data of 83,796 women with singleton pregnancies at and after 22 weeks of gestation (enrolled between 2011 and 2014) were analyzed. These data were obtained from the Japan Environment and Children's Study. Atopic dermatitis was defined based on self-reported questionnaire responses obtained during the first trimester. The primary outcome measures were preterm births before 37, 32, and 28 weeks of gestation. Using a multivariable logistic regression model, odds ratios for preterm births in pregnant women with atopic dermatitis were calculated, with women without atopic dermatitis included in the reference group. This analysis considered confounding factors and maternal ritodrine hydrochloride administration. RESULTS: Among pregnant women with atopic dermatitis, the adjusted odds ratios (95% confidence intervals) for preterm births before 37, 32, and 28 weeks of gestation were 0.89 (0.81-0.98), 0.98 (0.74-1.30), and 0.88 (0.50-1.55), respectively. This trend remained consistent after excluding participants who received ritodrine hydrochloride. CONCLUSIONS FOR PRACTICE: Atopic dermatitis in pregnant women was significantly associated with a decreased incidence of preterm births before 37 weeks of gestation, even after accounting for the effects of maternal ritodrine hydrochloride administration.

Association between preconception dietary fiber intake and hypertensive disorders of pregnancy: The Japan Environment and Children's Study.

OBJECTIVES: Hypertensive disorders of pregnancy (HDP) are a significant cause of morbidity and mortality. This study aimed to investigate whether preconception dietary fiber intake is associated with new-onset HDP. STUDY DESIGN: We identified 84,873 (primipara, 33,712; multipara, 51,161) normotensive participants from the Japan Environmental Children's Study database who delivered between 2011 and 2014. The participants were subsequently categorized into five groups based on their preconception dietary fiber intake quintiles (Q1-Q5). MAIN OUTCOME MEASURES: The main obstetric outcome was HDP, and the secondary obstetric outcomes included early-onset (Eo, <34 weeks)-HDP, late-onset (Lo, ≥34 weeks)-HDP, small for gestational age (SGA) births, and HDP with/without SGA. RESULTS: Multiple logistic regression analysis showed that in primiparas, the risks of HDP, Lo-HDP, and HDP without SGA were lower in the Q5 group compared with the Q3 group (HDP: adjusted odds ratio [aOR] = 0.73, 95 % confidence intervals [95 % CI] = 0.58-0.93; Lo-HDP: aOR = 0.72, 95 % CI = 0.55-0.94; and HDP without SGA: aOR = 0.68, 95 % CI = 0.53-0.88). However, the risks of Eo-HDP and HDP with SGA were higher in the Q1 group compared with the Q3 group (Eo-HDP: aOR = 1.66, 95 % CI = 1.02-2.70; and HDP with SGA: aOR = 1.81, 95 % CI = 1.04-3.17). In multiparas, the risks of Lo-HDP and SGA were higher in the Q1 group compared with the Q3 group (Lo-HDP: aOR = 1.47, 95 % CI = 1.10-1.97; SGA: aOR = 1.17, 95 % CI = 1.02-1.35). CONCLUSIONS: Preconception dietary fiber intake is beneficial in preventing HDP onset. Therefore, new recommendations should be considered to encourage higher dietary fiber intake as part of preconception care.

Efficacy of Lasmiditan as a Secondary Treatment for Migraine Attacks after Unsuccessful Treatment with a Triptan.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 h, patients took 50 mg of lasmiditan within 2 h of migraine onset. Patients recorded headache intensity and adverse events (AEs) caused by lasmiditan at 1, 2, and 4 h after the intake of an additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p < 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 h after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 h after lasmiditan intake. Our study revealed the significant headache relief provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short time. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

CONTEXT: Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). OBJECTIVE: To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. DESIGN: Prospective observational study using data from the Japan Environment and Children's Study (JECS). PARTICIPANTS: Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. MAIN OUTCOME MEASURES: Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. RESULTS: We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). CONCLUSIONS: The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Safety and efficacy of airway stent placement following bronchial artery embolization: A retrospective study at a single institute.

BACKGROUND: Airway stenting is an established procedure for treating oncological emergencies in patients with airway disorders. In patients with airway hemorrhage, respiratory conditions may worsen during stenting. Bronchial artery embolization (BAE) is useful to prevent bleeding from the bronchus. We aimed to evaluate the efficacy and safety of airway stenting after BAE in patients with malignant airway disorders. METHODS: The medical records of all patients who underwent airway stenting following BAE at the National Hospital Organization Okayama Medical Center between 2016 and 2023 were retrospectively reviewed. RESULTS: Thirteen procedures (11 silicone Y stents, one hybrid stent, and one self-expandable metallic stent) were performed. The median duration from BAE to airway stenting was one day (range: 1-5 days). Nine patients experienced tumor shrinkage, and none experienced severe bleeding after BAE during the stent procedure. No other major complications were associated with the stent placement. The median survival time after stenting was 169 days (range; 24-1086). No serious complications caused by BAE, such as spinal cord infarction, were observed. CONCLUSIONS: Airway stent placement was safely performed after BAE without severe bleeding or acute respiratory failure. BAE, followed by airway stenting, is useful.

Granular Cell Tumor Mimicking Breast Carcinoma: A Report of Two Cases.

Granular cell tumor (GCT) of the breast is a rare neoplasm that can mimic the clinical and radiological features of breast carcinoma. This paper presents two case reports - a rare male case and a more common female case - to underline the diagnostic challenges posed by GCT in the breast. The male patient was initially suspected of having a breast tumor based on mammography and ultrasound findings. The female patient also exhibited radiological signs suggestive of breast cancer. In both cases, the mammograms showed irregular lesions, while ultrasounds revealed solid masses with posterior shadowing and echogenic halos, mimicking carcinoma. Dynamic contrast-enhanced magnetic resonance imaging (MRI) suggested benign patterns in both cases, but only histopathologic examination post-core needle biopsy confirmed the diagnosis of GCT. These cases highlight the variability of GCT imaging presentations and the potential for misdiagnosis as breast carcinoma. The tumors exhibited distinct histopathological features, such as large polygonal cells with granular eosinophilic cytoplasm and S100 protein, differentiating them from breast carcinoma. However, imaging alone proved insufficient for diagnosis, emphasizing the need for histopathologic confirmation. The report discusses the importance of including GCT in differential diagnoses and utilizing core needle biopsy for accurate evaluation. Both cases had no recurrence during follow-up after wide resection, indicating a favorable prognosis for GCT when properly managed.

Airway stenosis secondary to mediastinal lymph node metastasis of lung adenocarcinoma treated with AERO stent and osimertinib: A case report.

A woman in her mid-50s was admitted to our hospital with airway stenosis secondary to mediastinal lymph node enlargement. An AERO stent was placed under rigid bronchoscopy. Immediately after stent placement, tissue sampling was performed on the lymph nodes. Metastatic lesions were found to have an EGFR mutation (exon 19 deletion). Consequently, osimertinib treatment was initiated 15 days after stent placement. The tumour partially responded to osimertinib, and the airway stenosis improved. The patient underwent stent removal 66 days after stent placement. Our findings indicate that temporary oncological emergencies due to airway stenosis may be bridged by airway stenting.

Autopsy case of meningoencephalitis induced by nivolumab and ipilimumab in a patient being treated for non-small cell lung cancer.

A 75-year-old woman with stage IVB (cT2bN3M1b) lung adenocarcinoma was administered nivolumab, ipilimumab, carboplatin, and paclitaxel. Fourteen days after receiving chemotherapy, she experienced an impaired consciousness and a cerebrospinal fluid analysis revealed high protein levels and pleocytosis. She was diagnosed with nivolumab- and ipilimumab-induced encephalitis and was treated with corticosteroids which were tapered to 10 mg/day, with no symptom recurrence. She died 18 weeks after the initial presentation, as the cancer worsened. An autopsy showed encephalitis and CD8+ lymphocyte infiltration around the blood vessels. Thus, immune-related adverse events should be suspected and treatment should be initiated for patients presenting with an impaired consciousness when concurrently being treated with nivolumab and ipilimumab.

Successful ultrathin bronchoscopy with cryobiopsy for diagnosing and removing mucus plugs in allergic bronchopulmonary mycosis mimicking lung cancer.

In patients presenting with abnormal pulmonary nodules, especially those with a history of asthma, allergic bronchopulmonary mycosis should be considered. Eosinophil counts and IgE levels should be checked in such patients.

Real-world retrospective study of repetitive transcranial magnetic stimulation (TMS) treatment for bipolar and unipolar depression using TMS registry data in Tokyo.

Despite the prevalence of empirical practice, evidence supporting the use of repetitive transcranial magnetic stimulation (rTMS) in treating bipolar depression (BD) is sparse compared to that for unipolar depression. Therefore, this study aimed to conduct a retrospective observational analysis using TMS registry data to compare the efficacy of rTMS treatment for BD and unipolar depression. Data from 20 patients diagnosed with unipolar and BD were retrospectively extracted from the TMS registry to ensure age and sex matching. The primary outcomes of this registry study were measured using the 21-item Hamilton Depression Rating Scale (HAM-D21) and Montgomery-Åsberg Depression Rating Scale (MADRS). Analysis did not reveal significant differences between the two groups in terms of depression severity, motor threshold, or stimulus intensity at baseline. Similarly, no significant differences were observed in absolute or relative changes in the total HAM-D21 and MADRS scores. Furthermore, the response and remission rates following rTMS treatment did not differ significantly between groups. The only adverse event reported in this study was scalp pain at the stimulation site; however, the incidence and severity were not significantly different between the groups. In conclusion, this retrospective study, using real-world TMS registry data, suggests that rTMS treatment for BD could be as effective as that for unipolar depression. These findings underscore the need for further validation in prospective randomized controlled trials with larger sample sizes.

Granulocyte-Colony Stimulating Factor (G-CSF)-Induced Aortitis: A Case Report.

Pegylated granulocyte colony-stimulating factor (G-CSF), commonly used in chemotherapy-induced neutropenia, has been associated with rare instances of aortitis. This study describes a 67-year-old female patient with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2-positive breast cancer, undergoing chemotherapy with an epirubicin/cyclophosphamide (EC) regimen (epirubicin, cyclophosphamide) and pegylated G-CSF for neutropenia prophylaxis. Post-treatment, she developed symptoms including intermittent fever and severe arthralgia. Laboratory tests revealed an elevated white blood cell count, C-reactive protein levels, and erythrocyte sedimentation rate, while a computed tomography scan showed thickening in the aortic arch and descending aorta. Given the clinical presentation and exclusion of other potential causes, pegylated G-CSF-induced aortitis was suspected. The patient's symptoms improved significantly following the cessation of pegylated G-CSF, aiding in the differentiation from other types of aortitis. This study highlights the importance of considering pegylated G-CSF as a potential cause of aortitis in patients presenting with unexplained symptoms of fever and inflammation after chemotherapy. The rapid improvement upon discontinuation of the drug is a key feature distinguishing it from other aortitis causes. In conclusion, while rare, aortitis should be considered in the differential diagnosis of patients treated with pegylated G-CSF who exhibit relevant clinical symptoms. Early detection and management, including the discontinuation of the causative agent, are crucial for patient recovery and prognosis.

Secondary Pulmonary Alveolar Proteinosis Development during the Treatment for Anti-aminoacyl-tRNA Synthetase Antibody-positive Interstitial Lung Disease.

A 70-year-old woman with anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease (ARS-ILD) received daily medications and regular cyclophosphamide cycles for recurring exacerbations. Approximately four years after immunosuppression initiation, the patient was admitted for progressive dyspnea on exertion. Chest computed tomography (CT) findings were suggestive of acute exacerbation. Despite intensified immunosuppressive treatment, the radiographic findings worsened, and serum Krebs von den Lungen-6 (KL-6) levels increased. A bronchoalveolar lavage fluid (BALF) examination revealed amorphous globules and alveolar macrophages with eosinophilic granules. Owing to negative anti-GM-CSF antibody tests, a diagnosis of secondary pulmonary alveolar proteinosis (PAP) was established.

Association between daily breakfast habit during pregnancy and neurodevelopment in 3-year-old offspring: The Japan Environment and Children's Study.

The association between daily breakfast habits during pregnancy and offspring neurodevelopment remains unknown. We evaluated the association between breakfast habits during pregnancy and offspring neurodevelopment. Data of 72,260 women with singleton deliveries at and after 37 weeks of gestation enrolled during 2011-2014 in the Japan Environment and Children's Study were analysed. Offspring neurodevelopmental delays at 3 years of age were evaluated using the Ages and Stages Questionnaire, Third Edition (ASQ-3). Participants were stratified by tertiles of maternal daily energy intake (DEI) (Groups 1, 2, and 3:< 1400, 1400-1799, and ≥ 1800 kcal, respectively) during pregnancy and by offspring sex. The adjusted odds ratio (aOR) for abnormality in communication among participants with daily breakfast consumption habit was 0.87 (95% confidence interval, 0.80-0.96). A stratified analysis based on total DEI showed no significant differences in the neurodevelopment of Group 1 offspring. The aOR for abnormality in communication was 0.80 (95% confidence interval, 0.68-0.94) in Group 2. The aOR for abnormality in personal-social characteristics was 0.84 (95% confidence interval, 0.71-0.99) in Group 3. Maternal daily breakfast habits are associated with offspring neurodevelopment at 3 years of age, with the association influenced by maternal DEI and offspring sex.

Gestational Age and Neurodevelopmental Delay in Term Births at 6 and 12 Months: The Japan Environment and Children's Study (JECS).

BACKGROUND: In the recent years, a high risk of developmental delay not only in very low birth weight infants and late preterm infants but also in early term infants (37-38 weeks) have increasingly been reported. However, in Japan, there are virtually no studies regarding the development delays in early term infants. METHODS: This study used the data from the Japan Environment and Children's Study (JECS), a birth cohort study conducted in Japan. Data were selected for analysis from the records of 104,065 fetal records. The risk of neurodevelopmental delays at 6 months and 12 months after birth was evaluated using multivariate analysis for infants of various gestational ages, using the 40th week of pregnancy as a reference value. Neurodevelopment was evaluated at 6 months and 12 months after birth using the Ages and Stages Questionnaires, Japanese translation (J-ASQ-3). RESULTS: The proportion of infants born at a gestational age of 37 to 38 weeks who did not reach the J-ASQ-3 score cutoff value was significantly higher in all areas at both 6 months and 12 months after birth, when compared to that of infants born at 40 weeks. The odds ratio decreased at 12 months after birth compared to that at 6 months after birth. CONCLUSION: Early term infants in Japan are at an increased risk of neurodevelopmental delay at 12 months after birth.