Tetsuji Kaneko

Inner segment/outer segment junction assessed by spectral-domain optical coherence tomography in patients with idiopathic epiretinal membrane.

PURPOSE To evaluate the anatomic features of the photoreceptor inner/outer segment (IS/OS) junction before and after surgery by spectral-domain optical coherence tomography in patients undergoing idiopathic epiretinal membrane (ERM) surgery and to correlate these features with the functional outcomes. DESIGN Prospective, cohort study. METHODS We prospectively studied 45 eyes of 45 patients with idiopathic epiretinal membrane who had a preoperative visual acuity of 20/32 or less and were scheduled to undergo transconjunctival 25-gauge vitrectomy. The patients were divided into 2 groups based on the preoperative structural integrity of the IS/OS junction: the intact IS/OS junction group and the disrupted IS/OS junction group. Changes in the IS/OS junction and best-corrected visual acuity were compared between 2 groups before and at 3, 6, and 12 months after surgery. RESULTS A total of 45 patients were recruited for this study. There were 34 eyes with an intact IS/OS junction (group 1) and 11 eyes with a disrupted or irregular IS/OS junction (group 2), as determined before surgery. Significantly better postoperative best-corrected visual acuity was seen in group 1 as compared with that in group 2 at 3, 6, and 12 months after the surgery (P < .001). Significant improvement of visual acuity was also seen in group 1 when compared to group 2 (P < .05). Of the 34 eyes in group 1, 17 (50%) showed disruption of the IS/OS junction at 3 months after surgery, although this disruption was only transient and resolved completely by 12 months after the surgery. However, none of the eyes from group 2 showed a normal appearance of the IS/OS junction at any time point during the study period of 1 year. CONCLUSIONS The IS/OS junction can recover in eyes with preoperative intact IS/OS junction as assessed over a follow-up period of 1 year after surgery. Preoperative integrity of the IS/OS junction may be an important prognostic factor for better visual recovery and better improvement of the postoperative best-corrected visual acuity after epiretinal membrane surgery.

Preoperative inner segment/outer segment junction in spectral-domain optical coherence tomography as a prognostic factor in epiretinal membrane surgery.

Purpose: To evaluate the macular structure on spectral-domain optical coherence tomographic (SD-OCT) images to predict the outcome of surgery for idiopathic epiretinal membrane. Methods: Forty-five eyes of 45 consecutive patients with idiopathic epiretinal membrane who had a preoperative visual acuity of ≤20/32 and were scheduled to undergo a transconjunctival 25-gauge vitrectomy were involved in this prospective cohort study. The best-corrected visual acuity (BCVA) and SD-OCT images of the fovea were examined before the surgery and at 3, 6, and 12 months after the surgery. Associations between the visual acuity parameters and the preoperative SD-OCT features, including the morphology of the photoreceptor inner segment/outer segment junction, macular thickness, presence/absence of retinal cysts, and presence/absence of a macular pseudohole, were investigated as predictors of the outcome of the surgery. The main outcome measures were the association between the macular microstructure on preoperative SD-OCT images and the visual acuity parameters, such as the BCVA, at 12 months after the surgery (postoperative BCVA) and the difference between the preoperative visual acuity and the postoperative BCVA. Results: A total of 45 patients were enrolled in this study. The postoperative visual acuity was significantly better for the eyes with an intact inner segment/outer segment junction on the preoperative SD-OCT images than for those with an irregular or a disrupted inner segment/outer segment junction on the images (P < 0.001). Better preoperative visual acuity was associated with better visual acuity at 12 months and a lesser degree of improvement in the visual acuity (P < 0.001, respectively). Conclusion: The presence of an intact inner segment/outer segment junction on the preoperative SD-OCT images was found to be an important predictor of better visual recovery and better postoperative BCVA after epiretinal membrane surgery.

Factors associated with lower Mini Mental State Examination scores in elderly Japanese diabetes mellitus patients

Cognitive impairment in elderly diabetic patients has generated considerable interest recently; however, the mechanism of the impairment remains to be elucidated. In the current study, factors associated with cognitive dysfunction in old diabetic patients were explored. A Mini Mental State Examination (MMSE) was performed on 907 of 1173 registered elderly Japanese diabetic subjects. To characterize the clinical features of diabetes, we examined indices of glycemic control, lipid metabolism, blood pressure and complications. Single regression analysis adjusted for age showed that shorter height, higher GDS 15 scores, lower serum albumin, history of cerebrovascular disease, the existence of diabetic nephropathy, no smoking habit, no drinking habit, and no occupation were associated with lower MMSE scores. Multiple regression analysis demonstrated that age (odds ratio (OR)=1.079; 95% confidence interval (CI)=1.011-1.150), GDS 15 scores (OR=1.139; 95% CI=1.045-1.243), serum albumin (OR=0.336; 95% CI=0.174-0.745), and history of cerebrovascular disease (OR=3.011; 95% CI=1.578-5.748) were the variables significantly associated with having lower MMSE scores.

Pre-dialysis chronic kidney disease in children: results of a nationwide survey in Japan

BACKGROUND Chronic kidney disease (CKD) in children is a progressive and intractable condition that may severely impair the childs growth, development and quality of life. Epidemiological information on pediatric CKD, particularly in Asians, is scant. METHODS We conducted a nationwide, population-based survey of Japanese children aged 3 months to 15 years with pre-dialysis CKD to examine the prevalence of pediatric CKD in Japan. CKD was classified according to newly established criteria derived from reference serum creatinine levels in Japanese children. Surveys were sent to 1190 institutions across Japan to report on cases of pediatric CKD managed as of 1 April 2010. RESULTS A total of 925 institutions (77.7%) responded. Information on 447 children was collected. When subdivided according to our diagnostic criteria, 70.5% of children had stage 3 CKD, 23.9% stage 4 and 5.6% stage 5. The estimated prevalence of Japanese children with CKD was 2.98 cases/100,000 children. Of 407 CKD cases with non-glomerular disease, 278 (68.3%) had congenital anomalies of the kidney and urinary tract (CAKUT). The newly established criteria showed good validity compared with existing criteria, including the abbreviated Schwartz equation. CONCLUSIONS Findings from the first nationwide survey of pre-dialysis CKD in Asian children indicate that the prevalence of stage 3-5 CKD in children in Japan aged 3 months to 15 years is 2.98 cases/100,000 children. Most children with CKD presented with non-glomerular disease, most frequently CAKUT. Improved management of CAKUT, including renoprotective treatment and urological intervention, is required.

Progression to end-stage kidney disease in Japanese children with chronic kidney disease: results of a nationwide prospective cohort study

BACKGROUND The risk of progressing to end-stage kidney disease (ESKD) and factors associated with progression in children with chronic kidney disease (CKD) are unclear, especially in Asian children. METHODS We started a nationwide, prospective cohort study of 447 Japanese children with pre-dialysis CKD in 2010, with follow-up in 2011. Progression to ESKD was analyzed by Kaplan-Meier analysis according to CKD stage. Cox regression analysis was used to identify risk factors for progression. RESULTS Data were analyzed for 429/447 children. Five patients died, of which four died before progression to ESKD. Fifty-two patients progressed to ESKD (median follow-up 1.49 years), including 9/315 patients with stage 3 CKD, 29/107 with Stage 4 CKD and 14/25 with Stage 5 CKD. One-year renal survival rates were 98.3, 80.0 and 40.9%, for Stages 3, 4 and 5 CKD, respectively. Risk factors for progression to ESKD included CKD stage [versus Stage 3; Stage 4: hazard ratio (HR) 11.12, 95% confidence interval (CI) 4.22-29.28, P < 0.001; Stage 5: HR 26.95, 95% CI 7.71-94.17, P < 0.001], heavy proteinuria (>2.0 g/g urine creatinine; HR 7.56, 95% CI 3.22-17.77, P < 0.001) and age ( < 2 years: HR 9.06; 95% CI 2.29-35.84, P = 0.002; after starting puberty: HR 4.88; 95% CI 1.85-12.85, P = 0.001). CONCLUSIONS In this cohort, 12.5% of children with pre-dialysis CKD progressed to ESKD with a median-follow-up of 1.49 years. Children with advanced (Stage 4/5) CKD were particularly likely to progress. To our knowledge, this is the first, nationwide, prospective cohort study of children with pre-dialysis CKD in Asia.

Association of HLA-A * 02:06 and HLA-DRB1 * 04:05 with clinical subtypes of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A*02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value <0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2–43.0). On the other hand, HLA-DRB1*04:05 was associated with polyarticular JIA (corrected P-value <0.001, OR 2.9, 95% CI 1.7–4.8). We found an association of HLA-A*02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1*04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A*02:06 and DRB1*04:05.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial

Background: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous “more versus less statins” trials. However, no clear evidence for more versus less statins has been established in an Asian population. Methods: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. Results: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73–0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. Conclusions: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.

Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features.

Superior mesenteric artery syndrome: risk factor for duodenal involvement in Henoch-Schönlein purpura.

Background:  The anatomical location of the third portion of the duodenum is between the superior mesenteric artery (SMA) and the abdominal aorta (AA). When the aorto‐mesenteric angle (AMA) is small and the aorto‐mesenteric distance (AMD) is short, the duodenum becomes tightly compressed between these two blood vessels. Severe compression can obstruct the duodenum, resulting in vomiting and abdominal pain. This clinical condition is termed superior mesenteric artery syndrome (SMA syndrome). The duodenum is frequently affected in Henoch–Schönlein purpura (HSP). The aim of the present study was to verify that duodenal anatomy mimicking SMA syndrome is a risk factor for duodenal involvement and abdominal pain in HSP.

Validation of RAPID3 using a Japanese version of Multidimensional Health Assessment Questionnaire with Japanese rheumatoid arthritis patients: Characteristics of RAPID3 compared to DAS28 and CDAI

Abstract Objectives. To validate Routine Assessment of Patient Index Data 3 (RAPID3) using a Japanese version of Multidimensional Health Assessment Questionnaire (MDHAQ) with Japanese rheumatoid arthritis (RA) patients and to describe the characteristics of RAPID3 by comparison with Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI). Methods. The original MDHAQ was translated into Japanese with minor cultural modifications and was translated back in English. Test–retest reliability was evaluated in 50 Japanese RA patients and further validation was performed in 350 Japanese RA patients recruited by seven rheumatologists. RAPID3, CDAI, and DAS28 were assessed on two consecutive visits. Results. The test–retest reliability and the internal reliability of RAPID3 were excellent. Spearmans correlation coefficients between RAPID3 score versus CDAI score and DAS28 score were 0.761and 0.555. However, the agreement measured by kappa (weighted) for RAPID3 category versus CDAI category and for RAPID3 category versus DA28 category were 0.225 (0.382) and 0.187 (0.336). The sensitivity and specificity of “RAPID3 ≤ 3 and swollen joint ≤ 1” for predicting Boolean remission were 90.0% and 93.4%, respectively. Conclusions. RAPID3 obtained by Japanese MDHAQ was validated with Japanese RA patients and the remission criteria were found to have excellent clinical utility in usual care.