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Urayama K.Y.,St Lukes Life Science Institute | Chokkalingam A.P.,University of California at Berkeley | Manabe A.,St. Lukes International Hospital | Mizutani S.,Tokyo Medical and Dental University
International Journal of Hematology

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and efforts to understand its etiology has followed a paradigm that common genetic variation in the presence of modifiable environmental factors contribute to disease risk. To date, there are numerous reports of candidate gene association studies suggesting an involvement of genetic loci in childhood ALL risk, but the general lack of consistency in results has underscored the need for careful interpretation and confirmation in additional well-designed studies. Complementary efforts using the genome-wide association study approach have shown indisputable evidence that common low penetrance genetic polymorphisms contribute to childhood ALL risk. However, current calculations show that these established disease loci only explain a portion of the total estimated contribution of common genetic variation on childhood ALL risk. Certain candidate gene loci previously examined likely contribute to this unexplained variation in risk, but the challenge moving forward will be to establish which ones based on the accumulating evidence. In this review, we describe the results of the most recent gene association studies in childhood ALL and discuss options for future efforts to advance this area of research. © 2012 The Japanese Society of Hematology. Source

Inagaki K.,St. Lukes International Hospital | Ohkoshi K.,St. Lukes International Hospital | Ohde S.,St Lukes Life Science Institute

Purpose: To perform optical coherence tomography imaging of retinal healing after conventional multicolor laser, pattern scanning laser, or micropulse laser treatment and compare the characteristics of each method. Methods: This was a single-center interventional case series study. Twenty-nine patients with macular edema underwent laser photocoagulation. Changes of retinal morphology because of laser-tissue interaction were assessed within 3 months by using a spectral-domain optical coherence tomography. Results: Immediately after conventional multicolor laser or pattern scanning laser treatment, a hyperreflective band appeared at the laser sites. The photoreceptor inner segment-outer segment line disappeared in all the patients treated with a conventional multicolor laser, but was intact in 22.2% (2/9 eyes) after pattern scanning laser. From 1 week to 1 month, the bands resolved. At 3 months, recovery of the inner segment-outer segment line surrounding the laser site was seen in all patients after conventional grid photocoagulation and pattern scanning laser. Retinal morphology did not change at any time during the observation period after subthreshold micropulse diode laser photocoagulation. Conclusion: The characteristic in vivo effects of retinal photocoagulation were monitored over time by spectral-domain optical coherence tomography. Changes of retinal morphology appeared less intense after pattern scanning laser than conventional grid laser treatment. Source

Urayama K.Y.,University of California at Berkeley | Urayama K.Y.,St Lukes Life Science Institute | Thompson P.D.,University of Manchester | Trachtenberg E.A.,Childrens Hospital Oakland Research Institute | Chokkalingam A.P.,University of California at Berkeley
Frontiers in Oncology

The enduring suspicion that infections and immunologic response may play a role in the etiology of childhood leukemia, particularly acute lymphoblastic leukemia (ALL), is now supported, albeit still indirectly, by numerous epidemiological studies. The cumulative evidence includes, for example, descriptive observations of a peculiar peak incidence at age 2-5 years for ALL in economically developed countries, clustering of cases in situations of population mixing associated with unusual patterns of personal contacts, associations with various proxy measures for immune modulatory exposures early in life, and genetic susceptibility conferred by variation in genes involved in the immune system. In this review, our focus is the extended major histocompatibility complex (MHC), an approximately 7.6 Mb region that is well-known for its high-density of expressed genes, extensive polymorphisms exhibiting complex linkage disequilibrium patterns, and its disproportionately large number of immune-related genes, including human leukocyte antigen (HLA). First discovered through the role they play in transplant rejection, the classical HLA class I (HLA-A, -B, and -C) and class II (HLA-DR, HLA-DQ, and HLA-DP) molecules reside at the epicenter of the immune response pathways and are now the targets of many disease susceptibility studies, including those for childhood leukemia. The genes encoding the HLA molecules are only a minority of the over 250 expressed genes in the xMHC, and a growing number of studies are beginning to evaluate other loci through targeted investigations or utilizing a mapping approach with a comprehensive screen of the entire region. Here, we review the current epidemiologic evidence available to date regarding genetic variation contained within this highly unique region of the genome and its relationship with childhood ALL risk. © 2013 Urayama, Thompson, Taylor, Trachtenberg and Chokkalingam. Source

Tsugawa Y.,Harvard Interfaculty Initiative in Health Policy | Tsugawa Y.,St Lukes Life Science Institute | Kumamaru H.,Harvard University | Yasunaga H.,University of Tokyo | And 3 more authors.
Medical Care

BACKGROUND: The association between hospital volume and patient outcomes remains unclear for stroke. Little is known about whether these relationships differ by stroke subtypes. OBJECTIVES: To examine the association of hospital volume with in-hospital mortality and costs of care for stroke. RESEARCH DESIGN: Secondary data analysis of national hospital database. SUBJECTS: A total of 66,406 patients admitted between July 1 and December 31, 2010 with primary diagnosis of stroke at 796 acute care hospitals in Japan were included. MEASURES: We used a locally weighted scatter-plot smoothing method to test the relationship between hospital volume and outcomes. On the basis of these results, we categorized patient volume into 3 groups (10-50, 51-100, and >100 discharges/6 mo). We tested the volume-outcome relationship using multivariable regression models adjusting for patient and hospital characteristics. Subgroup analysis was conducted by stratifying on stroke subtype. RESULTS: Compared with those treated at high-volume hospitals (>100 discharges), patients admitted to low-volume hospitals (10-50 discharges) had higher in-hospital mortality (adjusted odds ratio, 1.45; 95% CI, 1.23-1.71, P<0.0001). In the lowest volume hospitals, adjusted costs of care per discharge were 8.0% lower (95% CI, -14.1% to -1.8%, P=0.01) compared with the highest volume hospitals. The volume-mortality association was significant across all stroke subtypes. Highest volume hospitals had higher costs than lowest volume hospitals for subarachnoid hemorrhage, but this association was nonsignificant for ischemic and hemorrhagic stroke. CONCLUSIONS: Highest volume hospitals had lower mortality than the lowest volume hospitals for stroke in Japan. Highest volume hospitals had higher costs for subarachnoid hemorrhage, but not for ischemic and hemorrhagic stroke. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Okada K.,St. Lukes International Hospital | Ohde S.,St Lukes Life Science Institute | Otani N.,St. Lukes International Hospital | Sera T.,St. Lukes International Hospital | And 3 more authors.

Aim: To identify patients who can obtain the full benefit from targeted temperature management (TTM) after out-of-hospital cardiac arrest. Methods: We performed a retrospective observational study of comatose patients treated with TTM after an out-of-hospital cardiac arrest from January 2006 to February 2011. Neurological outcome was evaluated with the Glasgow-Pittsburgh Cerebral Performance category (CPC) at discharge and predictors were determined. Results: Of 66 patients studied, 40 (60.6%) survived to neurologically intact discharge (CPC 1 or 2). According to multivariate analysis, predictors of good neurological outcome included arrest-to-first cardiopulmonary resuscitation attempt interval ≤5. min, ventricular fibrillation or ventricular tachycardia in the first monitored rhythm, absence of re-arrest before leaving the emergency department, arrest-to-return of spontaneous circulation interval ≤30. min and recovery of pupillary light reflex, which were identifiable in the emergency department. Based on this analysis, we developed a seven-point score (5-R score). If the score was ≥5, it predicted good neurological outcome with a sensitivity of 82.5% (95% confidence interval [CI], 67.2-92.7%) and specificity of 92.3% (95% CI, 74.9-99.1%). The negative predictive value of a score ≥4 was 100% (95% CI, 81.5-100%). Our prediction model was validated internally by a bootstrapping technique. Conclusions: The prediction protocol using the 5-R score was associated with good neurological outcome of patients treated with TTM. Therefore, it could be helpful in clinical decision making on whether to initiate cooling. © 2012 Elsevier Ireland Ltd. Source

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