Clinical Features Of Japanese Patients Research Articles

Genetic and Clinical Features of ABCA4-Associated Retinopathy in a Japanese Nationwide Cohort

PurposeTo clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy. DesignRetrospective, multicenter cohort study MethodsPatients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression. ResultsThis study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including four with missense/missense and two with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks. ConclusionsOur results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials.

Clinical features of Japanese patients with gastrointestinal long-COVID symptoms.

Gastrointestinal (GI) long-COVID symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID. However, the clinical features of patients with GI long-COVID symptoms remain unclear. We conducted a large-scale prospective cohort study focusing on the clinical characteristics of patients with GI long-COVID symptoms in Japan. Among 943 COVID-19 patients, 58 patients (6.2%) had GI long-COVID symptoms. The health-related quality of life (QOL) parameters (the Short Form-8 [SF-8] and Euro Quality of Life 5 Dimensions 5 level [EQ-5D-5L]) at 12 months after diagnosis in patients with GI long-COVID symptoms were significantly lower than in those without GI long-COVID symptoms (P < 0.0001). Moreover, patients with GI long-COVID symptoms had more varied long-COVID symptoms compared to patients without GI long-COVID symptoms.

Analysis of clinical features of Japanese patients with primary ciliary dyskinesia

Analysis of clinical features of Japanese patients with primary ciliary dyskinesia

Effectiveness of Colchicine or Canakinumab in Japanese Patients with Familial Mediterranean Fever: A Single-Center Study.

Background: To investigate the clinical features of Japanese patients with Familial Mediterranean Fever (FMF), we evaluated the frequency of attacks, treatment responses, and adverse effects in 27 patients with FMF treated with colchicine or canakinumab in a real-world clinical setting. Methods: We retrospectively reviewed 27 Japanese patients with FMF treated at our institute between April 2012 and June 2023. All patients were diagnosed with FMF according to the Tel-Hashomer criteria. We performed genetic analyses of the MEFV gene using targeted next-generation sequencing. The clinical response was monitored through the number of attacks, and inflammatory markers were monitored through the C-reactive protein (CRP), and serum amyloid A (SAA) concentrations. Colchicine resistance was defined as the presence of at least one attack/month despite administration of the maximum tolerated dose of colchicine for at least 6 months, and C-reactive protein and serum amyloid A levels above the normal range between attacks. Results: A total of 27 patients diagnosed with FMF were enrolled in this study and the median follow-up period was 36.4 months. The median attack frequency was 1.0 (interquartile range: 0.33-1.0) every 3 months before treatment initiation. All the patients (n = 27) were treated with colchicine. Among the 27 patients, 20 (71.8%) showed a clinical response and 7 (25.9%) showed an incomplete response with sufficient doses of colchicine (n = 5) and non-sufficient doses (n = 2). Two patients on non-sufficient doses were unable to increase colchicine to the maximum dose due to diarrhea and liver dysfunction. All seven patients achieved a reduction in attack frequency after the initiation of canakinumab. No serious adverse events associated with canakinumab treatment were observed. In these seven patients with colchicine-resistant FMF (crFMF), the MEFV exon 10 variant was not detected, and the absence ratio of the MEFV variant was significantly higher compared to those without crFMF. Conclusions: Colchicine was effective in 71.8% (20/27) of Japanese patients with FMF; however, the remaining patients (7/27) had crFMF. Canakinumab effectively controlled febrile attacks in crFMF, even in the absence of pathogenic MEFV exon 10 variants.

Demographics and treatment of patients with primary nephrotic syndrome in Japan using a national registry of clinical personal records

The nationwide clinical features of Japanese patients with primary nephrotic syndrome (NS), including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN), have not yet been reported. We collected the clinical personal records of patients with primary NS between 2015 and 2018 from the national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Overall, the demographics, chronic kidney disease classification based on glomerular filtration rate and albuminuria, and treatment of 6036 patients were collected: 3394 (56.2%) with MCD, 677 (11.2%) with FSGS, 1455 (24.1%) with MN, and 510 (8.5%) with others. MN patients were older than MCD and FSGS patients (67 vs. 42 and 47 years, respectively). Steroid-dependent NS or frequently relapsing NS was found in 70.2%, 40.5%, and 24.6%, whereas steroid-resistant NS was found in 6.4%, 36.0%, and 37.9% of patients in the MCD, FSGS, and MN, respectively. The present oral prednisolone use (mean dose, mg/day) was 87.2% (21.2), 80.9% (20.0), and 77.5% (18.8) of patients in the MCD, FSGS, and MN, respectively. The national registry of clinical personal records of primary NS could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary NS in Japan.

Clinical features of Japanese patients with acute hepatic porphyria.

Acute hepatic porphyria (AHP) is a family of rare genetic diseases of heme biosynthesis characterized by severe neurovisceral attacks. The clinical characteristics of patients with AHP as well as the prevalence of AHP in Japan are not well understood. The objectives of this study were to describe clinical characteristics of AHP at time of diagnosis in Japanese patients and to estimate the prevalence of AHP. Patients with porphyria were selected from Japan's Medical Data Vision health care claims database between April 2008 and June 2020. Patient characteristics before and at time of AHP diagnosis were evaluated. Prevalence per 100 000 was estimated during the study period. A total of 391 cases of AHP were included. At time of AHP diagnosis, mean age was 44 years, and the most common type was acute intermittent porphyria. Median time to diagnosis was 3months, but some patients remained undiagnosed for several years. The most common complications included metabolic disorders (54%) and diabetes mellitus (39%). In addition, the well-known complications of AHP, including hypertension (22%) and malignant neoplasms of digestive organs (22%), were observed. About 10% of patients received medications that may have aggravated porphyria attacks. The estimated prevalence of AHP in Japan during the study period was 1.18 cases per 100 000 population. At time of diagnosis, many patients with AHP in Japan are already experiencing a high burden of disease-related complications. Raising AHP awareness may aid physicians in providing an earlier diagnosis and reducing lifetime disease burden.

Analysis of the clinical features of Japanese patients with primary ciliary dyskinesia

ObjectivePrimary ciliary dyskinesia (PCD) is a rare hereditary disease. Most reports of PCD in Japan are case reports, and clinical analysis has not been performed. Differences in the causative genes might affect the clinical features in different ethnic groups. The purpose of this study was to clarify the clinical features of Japanese patients with PCD. MethodsWe performed a retrospective chart review of PCD patients seen at Mie University Hospital and patients whose blood samples were sent to us for genetic analysis from 2011 to 2020. Data on the following items were collected and analyzed: age at first visit to the hospital, age at diagnosis of PCD, process of referral to our facility, chief complaint, situs status, PrImary CiliARy DyskinesiA Rule (PICADAR) score, nasal nitric oxide concentration, otoscopic findings, rhinoscopic findings, and paranasal computed tomography scan findings. ResultsSixty-seven patients (24 male, 43 female) were diagnosed with PCD during the study period. Age at diagnosis ranged from 2 months to 69 years (median, 17 years). Respiratory symptoms (77%) were the most common complaint, followed by nasal (15%) and aural (8%) symptoms. Situs inversus was present in 17 (25%) cases. Only 2 cases had congenital cardiac anomalies. The mean PICADAR score was 7.3 (range, 3–14) points. Approximately 50% of tympanic membranes showed retraction, suggesting otitis media with effusion. The mean Lund-Mackay score was 12.8 (range, 7–17) points, suggesting that the radiographic findings were not always severe. There was no significant difference in the total Lund-Mackay score between patients with and without situs inversus (12.7 vs. 12.6, respectively). ConclusionSitus inversus was present in 25% of Japanese PCD patients, which is much lower than observed in other countries. This is a result of differences in the major disease-causing genes. The general rule that “situs inversus is observed in approximately 50% of PCD patients” cannot be applied, at least, in Japanese PCD patients.

Narrative review of current COPD status in Japan.

Chronic obstructive pulmonary disease (COPD) causes morbidity and mortality worldwide. Due to the improvement in environmental sanitation and medical care, the general life span has increased in the past decades in Japan. However, many older patients with COPD develop a wide range of comorbidities, and the impairments in the activities of daily living result in frailty and increase social and economic burdens. Population-based studies have shown that the prevalence of COPD is approximately 10% among subjects aged ≥40 years, but more than 80% of COPD patients are underdiagnosed. The Ministry of Health, Labour, and Welfare in Japan proposed the National Health Promotion in the 21st century, termed Health Japan 21 (the second term), in 2013 to prevent the onset and progression of noncommunicable diseases (NCDs), including COPD. The government, medical society, and community have been attempting to increase the recognition of COPD and promote smoking cessation. Additionally, Japanese cohorts have revealed distinct clinical features in Japanese patients with COPD, including lower rates of patient-reported exacerbations, less frequent coexisting cardiovascular disease and metabolic syndrome, and lower use of inhaled corticosteroids in Japan compared to the Western countries. Moreover, the poor adherence to inhaled medications is found in approximately 20% of subjects, and rehabilitation is performed in 26% of hospitalized patients with COPD. Therefore, more efforts should be made to improve adherence and access to pulmonary rehabilitation. Overall, Japanese COPD patients share common clinical and social features with COPD patients in other countries. Further international corroboration may help establish better comprehensive management of the disease.

Clinical features of Japanese patients with exacerbations of chronic obstructive pulmonary disease

BackgroundExacerbations are critical events in chronic pulmonary obstructive disease (COPD). The frequency of COPD exacerbations is associated with the prognosis, including mortality, but no useful biomarker has been established.MethodsThe present retrospective study investigated 481 COPD patients. Clinical features in the stable period were compared between patients who experienced severe exacerbation (n = 88, 18.3%) and those who never experienced severe exacerbation (n = 393, 81.7%). In the patients who experienced exacerbations, clinical features were also compared between frequent exacerbators (exacerbation rate ≥ 2 times/year, n = 27, 30.7%) and infrequent exacerbators (1 time/year, n = 61, 69.3%).ResultsCompared to COPD patients who never experienced exacerbations, body mass index (BMI), serum albumin, and pulmonary functions were significantly lower, and the cardiovascular disease comorbidity rate, COPD assessment test score, modified Medical Research Council dyspnea scale, and use of long-term oxygen therapy, long-acting β2 adrenergic agonist therapy, inhaled corticosteroid therapy, and macrolide therapy were significantly higher in COPD patients with exacerbations (all p < 0.01). In patients who experienced exacerbations, frequent exacerbators had significantly lower % forced expiratory volume in 1.0 s and a higher risk of critical exacerbations, percentage of blood eosinophils, history of mechanical ventilation use, and use of long-term oxygen therapy and of macrolide therapy than infrequent exacerbators (all p < 0.01). On multivariate analysis, the percentage of blood eosinophils was the parameter most correlated with exacerbation frequency (β value [95% confidence interval] 1.45 [1.12–1.88], p < 0.01).ConclusionBlood eosinophil in the stable period is the factor most correlated with the frequency of severe exacerbations.Trial registration: The patients in this study was registered retrospectively

Baseline clinical features in a large-scale registration survey of patient with hypertrophic cardiomyopathy throughout Japan: J-HCM registry study

Abstract Background Hypertrophic cardiomyopathy (HCM) is a most prevalent primary myocardial disorder with heterogeneous clinical features. However, there have been few studies on clinical features of HCM as a prospective cohort. In 2015, we established a large-scale registration survey of patients with HCM throughout Japan, named J-HCM registry study. Purpose The aim of this study was to clarify the clinical features of Japanese patients with HCM. Methods J-HCM registry study is a prospective, multicenter investigation, consisting of 24 hospitals. This time, we present the baseline clinical characteristics in this survey. Results Total 1484 patients were registered. The ages at registration and at diagnosis were 65±15 and 56±17 years, respectively, and 806 patients (54%) were men. Majority of the patients (95%) was NYHA class I or II. With regard to subtypes of HCM, there were 526 patients (36%) in the HCM with left ventricular (LV) outflow tract obstruction, 126 patients (8%) in the mid-ventricular obstruction, 57 patients (4%) in the end-stage phase characterized by LV ejection fraction &amp;lt;50%, and 197 patients (14%) in apical HCM. At registration, 80 patients (6%) had prior successful recovery from sustained ventricular tachycardia or ventricular fibrillation, 162 patients (11%) suffered from heart failure hospitalization, and 64 patients (4%) had history of embolic event. Regarding invasive treatment, 160 patients (10%) had prior septal reduction therapy and 162 patients (11%) had ICD implantation. According to the 2014 European Society of Cardiology Guidelines on sudden cardiac death (SCD) prevention, the study patients were divided into 3 categories by the HCM Risk-SCD calculator: patients distribution, 4% in the high risk group (≥6% calculated HCM Risk-SCD at 5 years), 7% in the intermediate risk group (4% to &amp;lt;6%), 69% in the low risk group (&amp;lt;4%), and 16% in the patients with extreme characteristics (Figure 1). Conclusions In this multicenter registration survey of patients with HCM, the baseline clinical characteristics were almost similar to several retrospective large-scale cohorts in Western countries except older age and less symptomatic state. This study will provide important knowledge regarding management of HCM. Figure 1 Funding Acknowledgement Type of funding source: None

Anti-Zo antibodies in Japanese myositis patients detected by a newly developed ELISA.

The myositis-specific autoantibodies that characterise certain forms of idiopathic inflammatory myopathy (IIM) are useful for diagnosing dermatomyositis (DM) / polymyositis (PM) and predicting its prognosis. The autoantibody to phenylalanyl-tRNA synthetase (anti-Zo) has been identified as a disease marker antibody for anti-synthetase syndrome only in a UK cohort. Here we aim to establish an ELISA for the measurement of anti-Zo and to characterise the clinical features of Japanese patients who have this autoantibody. Anti-Zo was investigated by immunoprecipitation with recombinant phenylalanyl-tRNA synthetase α/β proteins. The results were confirmed by immunoprecipitation-Western blotting with cell extract. Sera from patients with DM/PM (n=224) were screened by an ELISA with the recombinant proteins. Medical records were retrospectively reviewed to obtain detailed information on the clinical phenotypes of the anti-Zo-positive patients. Only two male patients were confirmed to have anti-Zo. Both patients had fever, myopathy, interstitial lung disease, and mechanic's hands, and these clinical features are consistent with those of anti-synthetase syndrome. Another patient's serum showed a higher level than the cut-off value for anti-phenylalanyl-tRNA synthetase α by our in-house ELISA, but was judged to be negative for anti-Zo by immunoprecipitation-Western blotting. This is the first report of anti-Zo-positive IIM patients from Asia. Although Japanese patients with anti-Zo have a clinical phenotype similar to that of Caucasian patients, further large cohort studies are necessary to confirm the frequency of anti-Zo in Japanese IIM patients. Our newly developed ELISA should be validated for sensitivity and specificity in large cohorts.

Elucidation of predictors of disease progression in patients with relapsing polychondritis at the onset: potential impact on patient monitoring

BackgroundIn patients with relapsing polychondritis (RP), organ involvement developed in those with progressive and/or long disease courses. For their management, elucidation of a subgroup suggesting disease progression is awaited.MethodsWe previously conducted a physician’s questionnaire-based retrospective study to elucidate major clinical features of Japanese patients with RP. We here evaluated organ involvement at disease onset and at the last follow-up. We then counted cumulative numbers of involved organs at the last follow-up in 229 RP patients and compared them with involved organ numbers at disease onset, as possible indicators of disease progression. We assigned their prognosis at the last follow-up into “patient prognostic stages” from no medication (stage 1) to death (stage 5). We utilized nonparametric tests for group comparisons.ResultsInvolved organ numbers per-patient were 1.13 ± 0.03 at disease onset and 3.25 ± 0.10 at the last follow-up (disease duration was 4.69 ± 0.33 years), and increased along with the patient prognostic stages.At disease onset, 135 and 48 patients had auricular involvement (59% of 229 patients, defined as auricular-onset subgroup; AO) and respiratory involvement (21%, respiratory-onset subgroup; RO), respectively. 46 patients presented with other conditions (20%, miscellaneous-onset subgroup; MO) including CNS, ocular, and inner ear involvement, among others.RO patients showed worse (poorer) prognostic stages than AO patients. MO patients developed respiratory and/or auricular involvement thereafter and then showed significantly higher mortality rate (15%; 7/46) than AO patients (5.9%; 8/135).In RP patients who did not develop respiratory involvement until the last follow-up (throughout the disease course; 117 patients), mortality rate was 19% in 26 MO patients and 3.3% in 91 AO patients. Accordingly, RO patients and MO patients associated with relatively poor prognosis compared with AO patients.ConclusionsAllocation of patients to RO and MO subgroups was suggested to associate with poorer prognosis of RP than AO subgroups, especially AO subgroups without respiratory involvement throughout. All RP patients deserve careful monitoring but special attention should be paid to MO patients because of their diverse and accelerated disease progression.

&lt;p&gt;Clinical Features of Japanese Patients with Ocular Inflammation and Their Surgical Procedures Over the Course of 20 Years&lt;/p&gt;

PurposeTo review clinical characteristics of ocular inflammation patients in Osaka, Japan, over 20 years and investigate the efficacy of required surgeries.MethodsWe conducted a retrospective study involving 2730 eyes of 1815 patients with ocular inflammation examined at the Osaka Medical College Hospital from April 1999 to March 2019.ResultsPatients comprised 843 males and 972 females, with a mean age of 56.3 ± 18.5 years. Anterior uveitis, such as scleritis, acute anterior uveitis, and herpes iritis, was the most common anatomical classification (51.2%), followed by panuveitis (37.2%), posterior uveitis (9.4%), and intermediate uveitis (2.2%). Sarcoidosis occurred in 153 patients (8.4%), Vogt-Koyanagi-Harada disease (VKH) in 83 (4.6%), and Behçet’s disease in 68 (3.7%). Sarcoidosis peaked in two age groups: 30s and 50–70s. Of the 1815 patients, 389 eyes of 271 patients (14.9%) had cataract surgery, 162 eyes of 133 (7.3%) had vitrectomy, and 124 eyes of 103 (5.7%) had glaucoma surgery. Among cataract surgery patients, 49 (18.1%) had sarcoidosis, 14 (5.2%) had VKH, and seven (2.6%) had Behçet’s disease, and visual acuity (VA) was improved in 321 eyes (82.5%). Among vitrectomy patients, 15 (11.3%) had acute retinal necrosis, 14 (10.5%) had sarcoidosis, 12 (9.0%) had fungal endophthalmitis, and 11 (8.3%) had malignant lymphoma (ML); 83 eyes (51.2%) needed vitrectomy due to vitreous opacity, and VA improved in 88 eyes (54.3%). Among glaucoma surgery patients, 13 (12.6%) had sarcoidosis, and nine (8.7%) had Posner-Schlossman syndrome.ConclusionAnterior uveitis was the commonest form of uveitis and sarcoidosis was the commonest underlying disease. The age distribution of sarcoidosis was older than in previous reports. 10% of patients with sarcoidosis needed glaucoma surgery, and vitrectomy was required in 50% for vitreous opacity caused by ML or sarcoidosis.

P-82 Clinical features of Japanese patients with detailed RAS/BRAF mutant colorectal cancer

Mutated RAS/BRAF oncoproteins have been identified as key oncogenic drivers across the cancer types including colorectal cancer. Metastatic colorectal cancer (mCRC) patients with mutant RAS/BRAF are ineligible for anti-epidermal growth factor receptor (EGFR) therapy, as RAS/BRAF mutations activate downstream pathways independently of EGFR and induce primary resistance. In particular, KRAS mutations in the amino acid at position 12 in the KRAS protein are common. Nevertheless, previous attempts to therapeutically target mutant forms of KRAS have been unsuccessful, largely due to the lack of suitable drug-binding pockets on the protein.

P17 In-hospital mortality and clinical features of Japanese patients with acute myocardial infarction diagnosed by universal definition in real world from kanagawa-acute cardiovascular registry (K-ACTIVE)

Abstract Background Cardiac troponin (cTn) has been used as the preferred biomarker of myocardial injury for diagnosis of acute myocardial infraction (AMI) by universal definition. A large number of patients formerly classified by creatine kinase (CK) as unstable angina with the WHO criteria in Japan are now diagnosed by cTn as non-ST elevation myocardial infarction (NSTEMI). In this report, we aimed to understand its prevalence and clinical features of AMI diagnosed by using universal definition and the WHO criterial in real world. Method This registry is a cross-sectional study of 53 facilities in Kanagawa prefecture of Japan. 4372 AMI patients were enrolled who received primary percutaneous coronary intervention (PCI) between October 1, 2015 and January 29, 2019. Patients were divided into 3 groups, 3268 patients with ST elevation myocardial infarction (STEMI), 628 patients with NSTEMI patients who satisfied the WHO criteria with CK elevation beyond twice upper limit of normal (NSTEMI + CK), and 476 patients with NSTEMI who didn’t satisfy the WHO criteria without CK elevation (NSTEMI-CK). Result Baseline clinical characteristics of the study patients are shown in Table 1. In-hospital mortality was significantly lower in patients with NSTEMI-CK (1.9%) than in STEMI (6.0%, P &amp;lt; 0.001) and NSTEMI + CK (5.3%, P &amp;lt; 0.004) (Figure 1). Kaplan-Meier analyses for 0-30 days of cardiac death are shown in Figure 2. From day 0, the Kaplan-Meier curves began to diverge in favor of NSTEMI-CK for up to 30 days. Conclusion AMI patients showed distinct clinical features depends on the type. We should be aware of the difference for the diagnosis of AMI by using universal definitions. Table 1. STEMI (n = 3268) NSTEMI + CK (n = 628) NSTEMI-CK (n = 476) STEMI vs NSTEMI + CK P value STEMI vs NSTEMI-CK P value NSTEMI + CK vs NSTEMI-CK P value Age(years) 68(59-77) 69(61-78) 70(61-79) Male 76% 77% 75% 0.54 0.74 0.47 Concomitant diseases Hypertention 65.4% 70.5% 69.3% 0.013 0.097 0.65 Diabetes 33.5% 36.5% 37.3% 0.15 0.11 0.78 Dyslipidemia 56.1% 61.2% 61.3% 0.018 0.03 0.96 Hemodialysis 2.3% 2.1% 6.8% 0.86 &amp;lt;0.001 0.01 Smoking 66.3% 63.1% 64.6% 0.13 0.48 0.62 Atrial fibrillation 9.6% 10.7% 14.4% 0.57 0.04 0.23 Previous MI 8.3% 17.3% 15.7% &amp;lt;0.001 &amp;lt;0.001 0.47 In-hospital mortality 6.0% 5.3% 1.9% 0.49 &amp;lt;0.001 0.004 Abstract P17 Figure 1. 2.

PRRT2 mutations in Japanese patients with benign infantile epilepsy and paroxysmal kinesigenic dyskinesia

PurposeThis study was performed to clarify the clinical features of Japanese patients with PRRT2 mutations. MethodsThe PRRT2 gene was analyzed in 135 patients with benign infantile epilepsy (BIE) or paroxysmal kinesigenic dyskinesia (PKD) using a direct sequencing method: 92 patients had BIE alone, 25 had both BIE and PKD, and 18 had PKD alone. Of the cases, 105 were familial, and 30 were sporadic. Clinical information was collected using a structured questionnaire. ResultsPRRT2 mutations were identified in 104 patients. Among the familial cases, PRRT2 mutations were found in at least one individual in 21 of 28 families with BIE alone, in 26 of 27 families with infantile convulsions and choreoathetosis, and in 2 of 3 families with PKD alone. Among the sporadic cases, PRRT2 mutations were observed in 7 of 25 patients with BIE alone, in 1 of 1 patient with BIE and PKD, and in 3 of 4 patients with PKD alone. The c.649dupC mutation was the most frequent, followed by the c.981C > G mutation. Among the patients with epilepsy, the median age at BIE onset was 5 months, the median age at the last seizure was 6 months, and the median number of seizures was 5. ConclusionPRRT2 mutations were found in 68% of Japanese probands with BIE or PKD. The phenotypes of BIE associated with PRRT2 mutations were consistent with those of BIE diagnosed clinically.

Comparisons of Clinical Features in Japanese Patients with Behçet’s Uveitis Treated in the 1990s and the 2000s

ABSTRACTPurpose: We investigated clinical characteristics of ocular Behçet’s disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24–6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.

Clinical Features of Japanese Patients With Anti-α-enolase Antibody–Positive Autoimmune Retinopathy: Novel Subtype of Multiple Drusen

To evaluate clinical features of Japanese patients with anti-α-enolase antibody-positive autoimmune retinopathy (anti-enolase AIR). Multicenter retrospective observational case series. Forty-nine eyes of 25 Japanese anti-enolase AIR patients (16 female and 9 male; mean age at first visit, 60.8 years) were included. Fundus characteristics, perimetry, spectral-domain optical coherence tomography (SD-OCT), electroretinography (ERG), best-corrected visual acuity (BCVA), and complicating systemic tumors were assessed. Protein localization of α-enolase was examined by immunohistochemistry in an enucleated eye of 1 patient. Patients were classified into 3 groups: multiple drusen (48%), retinal degeneration (36%), and normal fundus (16%). Drusen varied in size from small deposits to vitelliform-like lesions. Images on SD-OCT revealed dome-shaped hyperreflectivity beneath the retinal pigment epithelium (RPE), corresponding to drusen. Perimetry showed that ring scotoma was the most frequent (39%). Rod-system and/or single-flash cone responses revealed decreased responses in 81% of the eyes. Combined rod and cone system responses demonstrated significantly lower a-wave amplitudes inthe degeneration group than in the drusen group (P= .005). BCVA was improved or maintained in 80% of the eyes during follow-up. Malignant or benign tumors were detected in 30% of patients. The RPE and photoreceptor layers were immunopositive for α-enolase. The drusen subtype, scarcely described in the literature, is suggested to characterize Japanese patients with anti-enolase AIR. The different funduscopic features with different functional severities may have resulted from antibody-mediated damage to RPE as well as photoreceptor cells.

Mutational subtypes of JAK2 and CALR correlate with different clinical features in Japanese patients with myeloproliferative neoplasms.

The majority of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) harbor JAK2, CALR, or MPL mutations. We compared clinical manifestations of different subtypes of JAK2 and CALR mutations in Japanese patients with MPNs. Within our cohort, we diagnosed 166 patients as polycythemia vera (PV), 212 patients as essential thrombocythemia (ET), 23 patients as pre-primary myelofibrosis (PMF), 65 patients as overt PMF, and 27 patients as secondary myelofibrosis following the 2016 WHO criteria. Compared to patients with JAK2V617F-mutated PV, JAK2 exon 12-mutated PV patients were younger, showed lower white blood cell (WBC) counts, lower platelet counts, higher red blood cell counts, and higher frequency of thrombotic events. Compared to JAK2-mutated ET patients, CALR-mutated ET patients were younger, showed lower WBC counts, lower hemoglobin levels, higher platelet counts, and fewer thrombotic events. CALR type 1-like mutation was the dominant subtype in CALR-mutated overt PMF patients. Compared with JAK2V617F-mutated ET patients, JAK2V617F-mutated pre-PMF patients showed higher LDH levels, lower hemoglobin levels, higher JAK2V617F allele burden, and higher frequency of splenomegaly. In conclusion, Japanese patients with MPNs grouped by different mutation subtypes exhibit characteristics similar to those of their Western counterparts. In addition, ET and pre-PMF patients show different characteristics, even when restricted to JAK2V617F-mutated patients.

Nationwide Survey of 741 Patients with Systemic Amyloid Light-chain Amyloidosis in Japan.

Objective To retrospectively investigate the clinical manifestations of systemic amyloid light-chain (AL) amyloidosis in Japanese patients and the treatment strategy for the condition. Methods We conducted a survey of Japanese AL amyloidosis patients, who were treated between January 1, 2012, and December 31, 2014. Results A total of 741 AL amyloidosis patients were included in this study (436 men and 305 women; median age: 65 years old, range: 31-93). The most frequently affected organ was the kidneys (n=542), followed by the heart (n=252), gastrointestinal (GI) tract (n=164), autonomic nervous system (n=131), liver (n=71), and peripheral nervous system (n=71). Diagnostic findings were most commonly detected in the GI tract (upper GI tract: 350 cases, lower GI tract: 167 cases), followed by the bone marrow and kidneys. An abdominal fat-pad biopsy was only conducted in 128 patients. Autologous stem cell transplants (ASCTs) and bortezomib were used to treat 126 and 276 patients, respectively. Conclusion The clinical features of Japanese patients with systemic AL amyloidosis are similar to those reported previously for cases in the US and Europe. Regarding treatment, a significant number of ASCTs were performed in Japan as well as in Western countries. Surprisingly, a marked number of patients received bortezomib as a treatment for AL amyloidosis.