The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children’s Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.

Granulomatosis with polyangiitis (GPA) is a rare disorder of unknown etiology, which is characterized by necrotizing granulomatous inflammation of the upper respiratory system and kidneys. Immunosuppressive treatment (cyclophosphamide or azathioprine with glucocorticoids) improved the outcome of GPA, however, latent comorbidity (cancers and hematologic malignancies) has become more prevalent in recent years. Here, we present a first case of the patient with GPA complicated by acute promyelocytic leukemia (APL) successfully treated with molecular-targeted therapy. A 77-year-old female was referred to our hospital for nasal obstruction, hearing loss, and fever. Otorhinolaryngological investigation revealed otitis media, and head computed tomography (CT) showed paranasal mucosal thickening with septal perforation. Chest CT showed cavitary granulomatous lesions in both lungs. Biopsy of the nasal mucosa revealed granulomatous lesions, and the patient was finally diagnosed with GPA. Oral administration of prednisolone 50 mg/day was initiated, and oral azathioprine (50 mg/day) was added. After 26 months of azathioprine initiation, pancytopenia developed and azathioprine was stopped. Then sudden elevated levels of blasts appeared in the hemogram (blasts 11%). She was diagnosed with APL via bone marrow examination which revealed plenty of faggot cells with Auer rods and chromosomal mutation. The patient was started on all-trans retinoic acid 60 mg/day following arsenic trioxide 7 mg/day in consideration of elderly onset. Complete remission was achieved and oral prednisolone was successfully reduced to 15 mg/day without a major relapse of GPA. Because GPA can be complicated by APL even during maintenance treatment using azathioprine, careful monitoring should be performed in such patients.

Lenalidomide (LEN), one of the key drugs in the treatment of myelodysplastic syndromes (MDS) with 5q deletion, as well as multiple myeloma (MM), has various immunomodulatory effects and has been associated with autoimmune diseases, including immune thrombocytopenic purpura (ITP). A 78-year-old man presented with pancytopenia and was diagnosed with MDS with 5q deletion and other chromosomal abnormalities. Two cycles of LEN therapy (one cycle: 10 mg/day for 21 days) resulted in a transient improvement in anemia, followed by MDS progression with severe thrombocytopenia (4 × 10⁹/L) refractory to platelet transfusions. As other non-immune and alloimmune causes of transfusion-refractory thrombocytopenia were excluded, and the level of platelet-associated immunoglobulin G was extremely high compared with the level before treatment with LEN, the diagnosis of ITP was highly suspected. Despite treatment with prednisolone (PSL), eltrombopag, and repeated platelet transfusions, his platelet count did not increase, and he died of a gastrointestinal hemorrhage. Several cases of ITP induced by LEN used to treat MM had been reported, but the platelet count recovered after administration of PSL in these previous cases. However, we should be mindful of using LEN for patients with MDS because its treatment may become extremely difficult if ITP develops.

Postreperfusion syndrome is one of the responsible mechanisms of portal hypertension in patients undergoing liver transplantation. And post-transplant portal hypertension causes graft dysfunction. Postreperfusion syndrome is characterized by a decrease in arterial pressure and cardiac output, and an increase in central venous pressure, pulmonary artery pressure, and pulmonary vascular resistance that occurs after the release of the portal vein clamp. Although early recovery from postreperfusion syndrome is desired, there is a little medication therapy such as the administration of calcium chloride, sodium bicarbonate, and beta-agonist for postreperfusion syndrome. We present a case of postreperfusion syndrome manifested as post-transplant portal hypertension and reversed after nitroglycerin administration. A 49-year-old Asian woman was scheduled for liver transplantation because of Budd-Chiari syndrome. After portal vein reperfusion, she experienced severe postreperfusion syndrome. Administration of ephedrine and calcium restored arterial pressure; however, pulmonary artery pressure, pulmonary vascular resistance, and central venous pressure elevations were sustained, causing right ventricular overload. This condition did not improve after hepatic artery reperfusion, and caused post-transplant portal hypertension. After nitroglycerin administration, pulmonary vascular resistance and central venous pressure decreased, mean arterial pressure increased, right heart contractility recovered, and portal hypertension disappeared. Hemodynamic improvement by nitroglycerin administration helped in diagnosing postreperfusion syndrome and avoiding unnecessary splenectomy. If portal vein pressure increases after liver transplantation, the change in hemodynamic parameters by nitroglycerin administration should be assessed, which will lead to accurate diagnosis and appropriate treatment. Furthermore, postreperfusion syndrome should be listed as a differential diagnosis of post-transplant portal hypertension.

Laparoscopic adrenalectomy is currently the standard treatment modality for unilateral aldosterone-producing adenoma (APA); however, a less-invasive treatment is needed for its treatment. A new bipolar ablation system that poses a lower risk of complications has been recently developed. This study aimed to evaluate the safety and performance of a novel bipolar radiofrequency ablation (RFA) system for the treatment of APAs. Ablations were performed in an ex vivo study using bovine adrenal glands [group A: n = 6, single-probe; group B: n = 6, two probes, interprobe distance (ID) = 12 mm; group C: n = 6, two probes, ID = 20 mm]. The in vivo study was conducted in groups A and B (n = 2 each) using porcine adrenal glands. For the ex vivo study, the mean vertical diameter (Dv) of the coagulative necrosis area and the mean transverse diameter (Dt) values were 11.99 mm and 10.96 mm for group A, 12.66 mm and 10.0 mm for group B, and 23.37 mm and 22.10 mm for group C, respectively. For the in vivo study, the mean Dv and Dt values were 12.23 mm and 9.03 mm for group A, and 16.38 mm and 9.52 mm for group B, respectively. No heat-induced damage to the adjacent organs was observed. To our best knowledge, this is the first study to evaluate the performance of the bipolar system in RFA of the adrenal gland. RFA using the new bipolar ablation system is safe and produces a sufficient coagulation area to treat APAs.

Endometriosis is a disease that is characterized by the ectopic presence of the endometrium or its similar cells. A high prevalence of patients with autoimmune diseases has been reported among patients with endometriosis although the cause of endometriosis remained unknown. Recently, the anti-lactoferrin antibody is reported to be highly detected in autoimmune diseases. This study focused on lactoferrin and anti-lactoferrin antibodies to explore the pathology of endometriosis. Lactoferrin is a substance that regulates inflammation and is produced by neutrophils. Anti-lactoferrin antibody is a type of perinuclear antineutrophil cytoplasmic antibody. The serum lactoferrin and anti-lactoferrin antibody levels were compared among patients with or without endometriosis, revealing significantly higher levels in patients with endometriosis. Additionally, a decreased serum anti-lactoferrin antibody level was observed after surgical endometriosis resection. The receiver operating characteristic curve analysis determined the reference values for the serum lactoferrin and anti-lactoferrin antibody levels. Patients whose serum level exceeded the reference anti-lactoferrin antibody value were significantly higher in more than 40% of cases in the endometriosis group. The rate is comparable to that of autoimmune diseases. This is the first report that anti-lactoferrin antibody is frequently observed in patients with endometriosis, adding a new perspective to the understanding of the pathology of endometriosis although precisely elucidating the mechanism by which lactoferrin and anti-lactoferrin antibody appear in endometriosis in the future is necessary.

Telemedicine has significant potential for helping workers access medical treatment. To improve workers’ access to telemedicine, it is important to analyze current utilization rates and influencing factors. Therefore, the purpose of this study is to evaluate the associations between occupational factors and telemedicine use. A 1-year follow-up study of 4,882 full-time workers receiving regular treatment in Japan was conducted from December 2020 to December 2021. Occupational factors associated with the use of telemedicine were evaluated by multivariate logistic regression analysis. In total, 191 participants had experience of using telemedicine (3.9%). The most common comorbidity was hypertension (37.0%), followed by back pain and arthritis (19.8%) and depression and psychiatric disorders (14.5%). Managers and executives [adjusted odds ratio (aOR) = 1.92, 95% confidence interval (CI): 1.68-3.43, P < = 0.026], finance industry workers (aOR = 2.61, 95% CI: 1.24-5.49, P = 0.011), and individuals with experience of teleworking (aOR = 2.08, 95% CI: 1.52-2.85, P < 0.001) were more likely to use telemedicine. Telemedicine usage was least common among workers aged 50-59 years (aOR = 0.35, 95% CI: 0.22-0.57, P < 0.001) and those with long working hours (≥ 9.0 hours/day) (aOR = 0.59, 95% CI: 0.38-0.93, P < 0.022). The utilization rate of telemedicine in Japan is still low. This study identified occupational factors related to the use of telemedicine, such as worker’s age, employee status, working hours, and experience of teleworking. Our findings suggest that flexible work arrangements could promote widespread use of telemedicine.

Heart failure is a major disease, and its 30-day readmission (readmission within 30-day after discharge) negatively impacts patients and society. Thus, we need to stratify the risk and prevent readmission. We aimed to investigate risk factors associated with 30-day readmission and examine the impact of length of hospital stay (LOS) on 30-day readmission. Using the Diagnosis-Procedure-Combination database from April 2018 to March 2021, we conducted multiple logistic regression to investigate risk factors with 30-day readmission. Also, we conducted subgroup analysis in the short LOS group. To examine the association between LOS and 30-day readmission, we performed propensity score matching between the short and middle LOS groups. As a result, we categorized 10,283 patients and 169,842 patients into the readmission group and the no-readmission group. We identified the following factors as the risk of readmission: short LOS, female, smoking, older age, lower body mass index, lower barthel index, artificial ventilator, beta-blockers, thiazides, tolvaptan, loop diuretics, carperitides, class Ⅲ antiarrhythmic agents, myocardial infarction, diabetes, renal disease, atrial fibrillation, dilated cardiomyopathy, and discharge to home. As a subgroup analysis in the short LOS group, we revealed that the short LOS group risk factors differed from overall. After propensity score matching in the short LOS group and middle LOS group, 37,199 pairs were matched, and we revealed that shorter LOS increases the risk of readmission. These results demonstrated that shortened LOS increases 30-day readmission, and risk factors are unique to each LOS. We suggest stratifying the readmission risk and being careful with early discharge.

Proinflammatory cytokines, reactive oxygen species and imbalance of neurotransmitters are involved in the pathophysiology of angiotensin II-induced hypertension. The hypothalamic paraventricular nucleus (PVN) plays a vital role in hypertension. Evidences show that microglia are activated and release proinflammatory cytokines in angiocardiopathy. We hypothesized that angiotensin II induces PVN microglial activation, and the activated PVN microglia release proinflammatory cytokines and cause oxidative stress through nuclear factor-kappa B (NF-κB) pathway, which contributes to sympathetic overactivity and hypertension. Male Sprague-Dawley rats (weight 275-300 g) were infused with angiotensin II to induce hypertension. Then, rats were treated with bilateral PVN infusion of microglial activation inhibitor minocycline, NF-κB activation inhibitor pyrrolidine dithiocarbamate or vehicle for 4 weeks. When compared to control groups, angiotensin II-induced hypertensive rats had higher mean arterial pressure, PVN proinflammatory cytokines, and imbalance of neurotransmitters, accompanied with PVN activated microglia. These rats also had more PVN gp91^phox (source of reactive oxygen species production), and NF-κB p65. Bilateral PVN infusion of minocycline or pyrrolidine dithiocarbamate partly or completely ameliorated these changes. This study indicates that angiotensin II-induced hypertensive rats have more activated microglia in PVN, and activated PVN microglia release proinflammatory cytokines and result in oxidative stress, which contributes to sympathoexcitation and hypertensive response. Suppression of activated PVN microglia by minocycline or pyrrolidine dithiocarbamate attenuates inflammation and oxidative stress, and improves angiotensin II-induced hypertension, which indicates that activated microglia promote hypertension through activated NF-κB. The findings may offer hypertension new strategies.