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"Suzuki, Kazuko"
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Divided fates
This book takes a cross-national and comparative approach, beyond American models, to examine how members of a single ethnic group adapt differently to distinct host societies. In her study of Korean immigrants to Japan and the United States, Suzuki finds that the state's mode of reception and its racialization of migrants determine adaptation patterns.
eBook
Phase Ib study of durvalumab (MEDI4736) in combination with carbon-ion radiotherapy and weekly cisplatin for patients with locally advanced cervical cancer (DECISION study): study protocol for a prospective open-label single-arm study
IntroductionConcurrent chemoradiotherapy is considered the standard treatment strategy for locally advanced cervical cancer. Most recent reports indicate that patients with bulky tumours or adenocarcinoma subtypes have poorer local control. Carbon-ion radiotherapy (CIRT) with the concurrent use of chemotherapy has shown promising results in such cases of difficult-to-treat uterine cervical cancer. Programmed death-ligand 1 (PD-L1) upregulation was observed in tumour tissue samples from patients who had undergone CIRT. Thus, a combination of CIRT and anti-PD-L1 antibody may suppress metastasis by activating antitumour immune response, in addition to exhibiting strong local effects.ObjectiveWe will assess the safety and tolerability (primary endpoint) of the concomitant use of durvalumab, an anti-PD-L1 antibody, with CIRT and weekly cisplatin for locally advanced cervical cancer.Methods and analysisThis study is a non-randomised, open-label, prospective phase 1b study. Up to 10 patients with histologically proven uterine cervical cancer at stage IIB, IIIA, IIIB, IIIC1 or IVA as per International Federation of Gynecology and Obstetrics (2018) staging will be enrolled. All patients will receive CIRT of 74.4 Gy relative biological effectiveness in 20 fractions over 5 weeks (four fractions per week). Weekly cisplatin at a dose of 40 mg/m2 will be administrated up to five times. Durvalumab at a dose of 1500 mg/body will be administrated at weeks 2 and 6. Safety and tolerability will be evaluated based on the frequency of dose-limiting toxicities until 92 days after CIRT starts. Patients will be followed-up strictly as per the scheduled protocol for 1 year after CIRT initiation.Ethics and disseminationThe Human Research Ethics Committees of QST Hospital (#C21-002) and Chiba University (#2021006) have approved this study protocol. The findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberJapan Registry of Clinical Trials (jRCT2031210083), registered on 12 May 2021.
Journal Article
A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results
We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.
Journal Article
Blood Pressure, Proteinuria, and Renal Function Decline: Associations in a Large Community-Based Population
BACKGROUND
Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population.
METHODS
We analyzed data from a nationwide database of 141,514 subjects who participated in the annual “Specific Health Check and Guidance in Japan” checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation.
RESULTS
After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria.
CONCLUSIONS
This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria.
Journal Article
Structural heterogeneity in and around the fold-and-thrust belt of the Hidaka Collision zone, Hokkaido, Japan and its relationship to the aftershock activity of the 2018 Hokkaido Eastern Iburi Earthquake
The Hokkaido Eastern Iburi Earthquake (M = 6.7) occurred on Sep. 6, 2018 in the southern part of Central Hokkaido, Japan. Since Paleogene, this region has experienced the dextral oblique transpression between the Eurasia and North American (Okhotsk) Plates and the subsequent collision between the Northeast Japan Arc and the Kuril Arc due to the oblique subduction of the Pacific Plate. This earthquake occurred beneath the foreland fold-and-thrust belt of the Hidaka Collision zone developed by the collision process, and is characterized by its deep focal depth (~ 37 km) and complicated rupture process. The reanalyses of controlled source seismic data collected in the 1998–2000 Hokkaido Transect Project revealed the detailed structure beneath the fold-and-thrust belt, and its relationship with the aftershock activity of this earthquake. Our reflection processing using the CRS/MDRS stacking method imaged for the first time the lower crust and uppermost mantle structures of the Northeast Japan Arc underthrust beneath a thick (~ 5–10 km) sedimentary package of the fold-and-thrust belt. Based on the analysis of the refraction/wide-angle reflection data, the total thickness of this Northeast Japan Arc crust is only 16–22 km. The Moho is at depths of 26–28 km in the source region of the Hokkaido Eastern Iburi Earthquake. Our hypocenter determination using a 3D structure model shows that most of the aftershocks are distributed in a depth range of 7–45 km with steep geometry facing to the east. The seismic activity is quite low within the thick sediments of the fold–thrust belt, from which we find no indication on the relationship of this event with the shallow (< 10–15 km) and rather flat active faults developed in the fold-and-thrust belt. On the other hand, a number of aftershocks are distributed below the Moho. This high activity may be caused by the cold crust delaminated from the Kuril Arc side by the arc–arc collision, which prevents the thermal circulation and cools the forearc uppermost mantle to generate an environment more favorable for brittle fracture.
Journal Article
Serum uric acid levels and mortality in the Japanese population: the Yamagata (Takahata) study
Background
Serum uric acid level is regulated by gender, dietary habit, genetic predisposition, and renal function, and is associated with the development of renal and cardiovascular diseases. This study prospectively investigated the association between serum uric acid levels and mortality in a community-based population.
Methods
Three thousand four hundred and eighty-seven subjects regardless of the antihyperuricemic medication (45 % male; mean age 62 years old) from the Takahata town in Japan participated in this study and were followed up for 8 years (median 7.5 years). We examined the association between serum uric acid levels at baseline and the all-cause and cardiovascular mortality, respectively, in this population.
Results
One hundred seventy-nine subjects died during the follow-up period, with 49 deaths attributed to cardiovascular causes. Kaplan–Meier analysis revealed that the all-cause mortality was significantly higher along with the increase in serum uric acid levels at baseline among female (Log-rank
P
< 0.01), but not male subjects (
P
= 0.97). Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia (uric acid ≥7.0 mg/dL) was an independent risk factor for all-cause and cardiovascular mortality, respectively, in female [hazard ratio (HR) 5.92, 95 % confidence interval (CI) 2.10–14.6 for all-cause mortality, and HR 10.7, 95 % CI 1.76–50.2 for cardiovascular mortality], but not male subjects.
Conclusion
Hyperuricemia was an independent risk for all-cause and cardiovascular mortality in female, but not among the male subjects in a community-based population.
Journal Article
The association between serum uric acid and renal damage in a community-based population: the Takahata study
Background
Hyperuricemia is a risk factor for end-stage renal disease. This study examined the association between serum uric acid and renal damage in a community-based population.
Methods
In this study 3126 subjects without renal insufficiency were recruited at baseline and were followed for one year. The urinary albumin–creatinine ratio (UACR) and β
2
-microglobulin–creatinine ratio (UBCR) in morning spot urine samples were used as indices of either glomerular (UACR) or tubular (UBCR) damage.
Results
The mean value of serum uric acid (mg/dL) was 5.8 ± 1.3 (SD) in men and 4.5 ± 1.1 in women. In cross-sectional analysis the increased serum uric acid levels were accompanied by higher UACR values in both men and women (
P
< 0.01). In contrast, UBCR values were reduced when uric acid levels increased in both men and women (
P
< 0.01). Multivariate analysis revealed that albuminuria (UACR ≥ 30 mg/g) was significantly associated with increased uric acid (≥7 mg/dL for men, ≥6 mg/dL for women). High UBCR (≥300 μg/g) was negatively associated with uric acid in men, but not in women, after adjustment for possible confounders. In longitudinal analysis in 1388 subjects multiple linear regression analysis showed that uric acid at baseline was an independent factor for one-year increase of UACR [coefficient 4.80 (95 % confidence interval 0.40–9.33) (mg/g) per 1 mg/dL increase in uric acid,
P
= 0.033].
Conclusion
This study showed that serum uric acid concentration was positively associated with UACR, suggesting that uric acid may be related to glomerular damage in a community-based population.
Journal Article
Comparison of the predictive ability of albuminuria and dipstick proteinuria for mortality in the Japanese population: the Yamagata (Takahata) study
Background
Albuminuria and proteinuria are known risk factors for premature death. This study compared the ability of albuminuria and proteinuria to predict mortality in a community-based population.
Methods
We evaluated the urinary albumin creatinine ratio (ACR) and proteinuria by dipstick at a baseline survey and examined the association between the 7-year mortality and three categories (albuminuria [ACR ≥ 30 mg/g], trace proteinuria, and ≥[1+] proteinuria) in 3446 Japanese subjects at a local health check.
Results
Albuminuria, ≥trace proteinuria, and ≥(1+) proteinuria were identified in 514 (14.9 %), 290 (8.4 %), and 151 (4.4 %) subjects, respectively. There were 138 deaths during the follow-up period, including 41 cardiovascular deaths. A Kaplan–Meier analysis showed that all-cause mortality significantly increased along with the increase in ACR and proteinuria levels (log-rank
P
< 0.01). The mortality rate (deaths per 1000 person-year) was higher in subjects with albuminuria (12.8), ≥trace proteinuria (12.6), and ≥(1+) proteinuria (16.2) than in all subjects (6.9). A Cox proportional hazard model analysis showed that all three categories were significant predictors of all-cause mortality in the unadjusted model, although after adjustment for possible confounders, a significant association was observed only with albuminuria. Albuminuria, but not proteinuria, was a significant predictor of cardiovascular mortality in both the unadjusted and adjusted models.
Conclusion
Albuminuria had a high prevalence and was strongly associated with mortality, as compared with proteinuria by dipstick, suggesting that albuminuria might be a superior predictor of poor prognosis in the Japanese population.
Journal Article