繰り返しイベントデータに対する動的予測 : 動的擬似値を用いたランドマークアプローチ

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 大江 和彦, 東京大学教授 小山 博史, 東京大学准教授 近藤 尚己, 東京大学教授 康永 秀生, 東京大学特任講師 建石 良介University of Tokyo(東京大学

Prospective Study on the Incidence of Bone Metastasis (BM) and Skeletal-Related Events (SREs) in Patients (pts) with Stage IIIB and IV Lung Cancer—CSP-HOR 13

Background:Bone metastasis (BM) is a frequent complication in patients with advanced lung cancer and it causes skeletal-related events (SREs). Our study aim is to prospectively investigate the incidence of BM, incidence and types of SRE, and predictive factors of BM and SREs.Methods:Newly diagnosed, advanced non–small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) patients were enrolled into the study. Patients were followed up every 4 weeks to monitor the development of SREs. Treatment for lung cancer was performed at the discretion of the investigator.Results:Two hundred seventy-four patients were enrolled in this study between April 2007 and December 2009 from 12 institutions. Patients included 77 cases of SCLC and 197 of NSCLC (stage IIIB/IV = 73/124). Median follow-up time was 13.8 months. The incidence of BM at initial diagnosis was 48% in stage IV NSCLC and 40% in extensive stage (ED)-SCLC. Forty-five percent of patients who developed BM had SREs consisting of pathologic fracture (4.7%), radiation to bone (15.3%), spinal cord compression (1.1%), and hypercalcemia (2.2%). Multivariate analysis revealed that factors predicting BM are stage IV, performance status 1 or greater and higher bone alkaline phosphatase in NSCLC patients, higher lactate dehydrogenase, and lower parathyroid hormone–related peptide in SCLC patients. Factors predicting SREs were stage IV, age 64 or younger, and lower albumin in NSCLC patients. Multivariate analysis of SRE was not performed for SCLC because of the small number of events.Conclusion:Predictive factors should be taken into consideration in future randomized studies evaluating BM and SREs

Latent trajectory modelling of pulmonary artery pressure in systemic sclerosis: a retrospective cohort study

OBJECTIVES: To visualise the trajectories of pulmonary arterial pressure (PAP) in systemic sclerosis (SSc) and identify the clinical phenotypes for each trajectory, by applying latent trajectory modelling for PAP repeatedly estimated by echocardiography. METHODS: This was a multicentre, retrospective cohort study conducted at four referral hospitals in Kyoto, Japan. Patients with SSc who were treated at study sites between 2008 and 2021 and who had at least three echocardiographic measurements of systolic PAP (sPAP) were included. A group-based trajectory model was applied to the change in sPAP over time, and patients were classified into distinct subgroups that followed similar trajectories. Pulmonary hypertension (PH)-free survival was compared for each trajectory. Multinomial logistic regression analysis was performed for baseline clinical characteristics associated with trajectory assignment. RESULTS: A total of 236 patients with 1097 sPAP measurements were included. We identified five trajectories: rapid progression (n=9, 3.8%), early elevation (n=30, 12.7%), middle elevation (n=54, 22.9%), late elevation (n=24, 10.2%) and low stable (n=119, 50.4%). The trajectories, in the listed order, showed progressively earlier elevation of sPAP and shorter PH-free survival. In the multinomial logistic regression analysis with the low stable as a reference, cardiac involvement was associated with rapid progression, diffuse cutaneous SSc was associated with early elevation and anti-centromere antibody was associated with middle elevation; older age of onset was associated with all three of these trajectories. CONCLUSION: The pattern of changes in PAP over time in SSc can be classified into five trajectories with distinctly different clinical characteristics and outcomes

Ectopic thyroid in an adrenal mass: a case report

BACKGROUND: It is difficult to explain ectopic thyroid beneath the diaphragm because during the development the thyroid descends from the tongue to the anterior of the trachea. A few cases of ectopic lesions have been reported in the literature for abdominal organs including the adrenal glands, but the mechanism by which the thyroid components migrate into the abdomen has been poorly understood. CASE PRESENTATION: A 54-year-old woman was diagnosed as having an adrenal mass. Laparoscopic adrenalectomy was carried out. Microscopically, the mass was composed of normal adrenal and ectopic thyroid tissues. CONCLUSION: We herein describe the fourth case reported of ectopic thyroid in the adrenal gland

Langerhans cell histiocytosis on the penis: a case report

BACKGROUND: Langerhans cell histiocytosis affects mainly young children and features an accumulation of CD1a+ dendritic Langerhans cells in the bone, skin, and other organs. A few cases of Langerhans cell histiocytosis on the penis have been reported in the literature. We present a case of Langerhans cell histiocytosis on the penis and review the similar cases in the literature. CASE PRESENTATION: The patient was a 13-year-old boy who had a history of lymph node, femur bone, and pituitary-thalmic axis lesions from Langerhans cell histiocytosis who noticed a painful nodule on the prepuce of his penis. The histological and immunohistochemical examination fulfilled the criteria of Langerhans cell histiocytosis. CONCLUSION: We herein describe the case reported of Langerhans cell histiocytosis on the penis

Multiple transcripts of Ca 2ϩ channel ␣ 1 -subunits and a novel spliced variant of the ␣ 1C -subunit in rat ductus arteriosus

3 H]thymidine incorporation, suggesting that L-and T-type Ca 2ϩ channels are involved in smooth muscle cell proliferation in the DA. Third, we found that a novel alternatively spliced variant of the ␣ 1C-isoform was highly expressed in the neointimal cushion of the DA, where proliferating and migrating smooth muscle cells are abundant. The basic channel properties of the spliced variant did not differ from those of the conventional ␣1C-subunit. We conclude that multiple VDCC subunits were identified in the DA, and, in particular, ␣ 1C-and ␣1G-subunits were predominant in the DA. A novel spliced variant of the ␣1C-subunit gene may play a distinct role in neointimal cushion formation in the DA. alternative spliced; development; gene expression; fetal circulation THE DUCTUS ARTERIOSUS (DA) is a fetal arterial connection between the pulmonary artery and the descending aorta. After birth, the DA closes immediately, in accordance with its smooth muscle contraction. An increase in oxygen tension and a dramatic decline in circulating prostaglandins are the most important triggers of DA contraction (5). Generally, vascular smooth muscle contraction is induced by Ca 2ϩ / calmodulin-dependent phosphorylation of the regulatory myosin light chain, which is mediated by an increase in intracellular Ca 2ϩ . Ca 2ϩ influx through voltage-dependent Ca 2ϩ channels (VDCCs) and Ca 2ϩ release from intracellular stores are major sources of this increase (8, 26). Thus VDCCs must play an important role in vascular myogenic reactivity and tone of the DA. VDCCs are classified, according to their distinct electrophysiological and pharmacological properties, into low (Ttype) and high (L-, N-, P-, Q-, and R-type) VDCCs (20, In addition to their role in determining contractile state, a growing body of evidence has demonstrated that VDCCs play an important role in regulating differentiation and remodeling of vascular smooth muscle cells (SMCs) (14, In the present study, we identified multiple VDCC subunits in the DA by semiquantitative and quantitative RT-PCR and immunodetection. In particular, ␣ 1C -and ␣ 1G -subunits were predominant in the DA. Furthermore, we will demonstrate the identification of a novel spliced variant of the ␣ 1C -subunit gene that may play a role in neointimal cushion formation of the DA

Age-Dependent Association Between Modifiable Risk Factors and Incident Cardiovascular Disease

BACKGROUND: There have been limited data examining the age-dependent relationship of wide-range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age-related associations between modifiable risk factors and the incidence of CVD. METHODS AND RESULTS: We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age cat-egory. Over a mean follow-up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years. CONCLUSIONS: The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.</p

Validity of the Short Nutritional Assessment Questionnaire for Japanese Patients with Cancer Undergoing Outpatient Chemotherapy

Purpose : To investigate the utility of the Short Nutritional Assessment Questionnaire (SNAQ) in the nutritional evaluation of patients with cancer undergoing outpatient chemotherapy. Methods :We included 229 patients with cancer who were undergoing outpatient chemotherapy between October 2015 and April 2016. The SNAQ and the revised SNAQ (addition of age and body mass index) were implemented, and their relationships with Controlling Nutritional Status (CONUT), an indicator of bionutritional assessment, were examined. Results : The cutoff value of the SNAQ score corresponding to moderate-to-severe undernourishment in CONUT values was 0.5, with a sensitivity of 87.5% and a specificity of 65.9%, and the corresponding values for the revised SNAQ score were 2.5, 91.7%, and 62.9%, respectively. This cutoff value and the corresponding positive prediction value for the revised SNAQ were superior to those of SNAQ. Binary logistic regression analysis with the revised SNAQ and sex as independent variables and the CONUT value as the dependent variable revealed that the higher the SNAQ score, the more likely it was that CONUT moderate-to-severe undernourishment would be identified (odds ratio, 1.48 ; , 1.34-1.96) . Conclusion : Nutritional evaluation with the revised SNAQ can predict moderateto- severe undernourishment according to CONUT in patients with cancer undergoing outpatient chemotherapy