The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease.

Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect. Using whole-exome sequencing, the c.1617del variant was identified in two siblings with PTA in a Japanese family and in three of the 26 DNAs obtained from Japanese individuals with PTA. The c.1617del of TMEM260 has been found only in East Asians, especially Japanese and Korean populations, and the frequency of this variant in PTA is estimated to be next to that of the 22q11.2 deletion, the most well-known genetic cause of PTA. Phenotype of patients with c.1617del appears to be predominantly in the heart, although TMEM260 is responsible for structural heart defects and renal anomalies syndrome (SHDRA). The mouse TMEM260 variant (p.W535Cfs*56), synonymous with the human variant (p.W539Cfs*9), exhibited truncation and downregulation by western blotting, and aggregation by immunocytochemistry. In situ hybridization demonstrated that Tmem260 is expressed ubiquitously during embryogenesis, including in the development of cardiac OFT implicated in PTA. This expression may be regulated by a ~ 0.8 kb genomic region in intron 3 of Tmem260 that includes multiple highly conserved binding sites for essential cardiac transcription factors, thus revealing that the c.1617del variant of TMEM260 is the major single-gene variant responsible for PTA in the Japanese population.

The relationship between equol production status and normal tension glaucoma.

PURPOSE: Equol is metabolized by intestinal bacteria from soy isoflavones and is chemically similar to estrogen. Dietary habits, such as consumption of soy products, influence equol production. A relationship between glaucoma and estrogen has been identified; here, we investigated the relationship between equol production status and glaucoma in Japan. METHODS: We recruited 68 normal-tension glaucoma (NTG) patients (male to female ratio 26:42, average age 63.0 ± 7.6 years) and 31 controls (male to female ratio 13:18, average age 66.0 ± 6.3 years) from our hospital. All women included were postmenopausal. Urinary equol concentration was quantified with the ELISA method. MD was calculated based on the Humphrey visual field. The association between MD and equol was analyzed with Spearman's rank correlation coefficient. The Mann-Whitney U test was used to compare the equol-producing (> 1 µM) and non-producing (< 1 µM) subjects. We also investigated the association between equol and glaucoma with a logistic regression analysis. RESULTS: There was a significant association between equol and MD (r = 0.36, P < 0.01) in the NTG patients. Glaucoma, represented by MD, was significantly milder in the equol-producing subjects than the non-equol producing subjects (P = 0.03). A multivariate analysis revealed the independent contributions of equol, cpRNFLT, and IOP to MD (P = 0.03, P = 0.04, and P < 0.01, respectively). CONCLUSION: Our results suggest that equol, acting through estrogen receptor-mediated neuroprotective effects, might be involved in suppressing the progression of NTG. This result also adds to evidence that glaucoma may be influenced by lifestyle.

Changes in glial cells and neurotrophic factors due to rotenone-induced oxidative stress in Nrf2 knockout mice.

Glaucoma is one of the most common causes of blindness worldwide. It is thought to be a multifactorial disease with underlying mechanisms that include mitochondrial dysfunction and oxidative stress. Here, we used NF-E2 related factor 2 (Nrf2) knockout (KO) mice, which are vulnerable to oxidative stress, to examine a neuroprotective effect against oxidative stress due to rotenone, a mitochondrial complex I inhibitor. Wild-type (WT) and Nrf2 KO mice received an oral solution of rotenone for 30 days. We then extracted the retinas and performed immunohistochemistry and quantitative RT-PCR. We also prepared a primary Müller cell culture of samples from each mouse, added 30 µM rotenone, and then measured cell viability, cytotoxicity and CellRox absorbance. We also examined gene expression. We found a significant increase in the number of 8-OHdG-positive retinal ganglion cells (RGCs) after rotenone administration in both the WT and Nrf2 KO mice. There was no difference in the number of RNA-binding protein with multiple splicing (RBPMS)-positive RGCs in the WT and Nrf2 KO mice, but Nrf2 KO mice that were given rotenone had significantly less retinal gene expression of RBPMS than Nrf2 KO mice given a control. Moreover, there was significantly higher mRNA gene expression of vimentin and glial fibrillary acidic protein (GFAP) in Nrf2 KO mice that received rotenone than WT mice that received rotenone. A statistical analysis of the in vitro experiment showed that cell viability was lower, cytotoxicity was higher, and oxidative stress was higher in the Müller cells of the Nrf2 KO mice than the WT mice. Finally, brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) were significantly higher in the Müller cells of the Nrf2 KO mice than the WT mice. These findings suggest that in Nrf2 KO mice under oxidative stress caused by rotenone, temporary neurotrophic factors are secreted from the Müller cells, conferring neuroprotection in these cells.

Pediatric blood pressure category predicts longitudinal blood pressure change in adolescence and early adulthood.

BACKGROUND: Patterns of blood pressure (BP) change from early adolescence to young adulthood have not been well-described. The objective of this study was to examine the predictive value of pediatric BP classification on BP change and identify subpopulations with large BP increases during adolescence and early adulthood. METHODS: Baseline data were obtained from medical checkups of Japanese adolescents aged 12-13 years in 2009 or 2010 and subsequent BP values were followed for a 9-year period. Mixed-effects models were used to estimate the effects of baseline factors on subsequent BP changes. RESULTS: Hypertensive and elevated BP group consistently had higher BP values than normal BP group throughout the observation period. Multivariate mixed-effects model analyses revealed group-by-time interactions between systolic BP change and BP category in males and uric acid category in females, and between diastolic BP change and white blood cell count in males and obesity and high-density lipoprotein cholesterol in females; however, these factors had limited effects on the rate of BP increase, indicating that they are not suitable as clinical predictors of BP increase. CONCLUSIONS: Pediatric BP category predicted BP values, but there was no factor that identified subpopulations with large BP increases in adolescence and early adulthood. IMPACT: Blood pressure category in the American Academy of Pediatrics clinical practice guideline at age 12-13 years predicted subsequent blood pressure values during adolescence and early adulthood. No baseline factor that identified a subpopulation with large increase in blood pressure during adolescence and early adulthood in clinical practice was found. Our study contributes to the existing literature by demonstrating the usefulness of the American Academy of Pediatrics clinical practice guideline for blood pressure classification in a Japanese population.

Genetic and functional analyses of TBX4 reveal novel mechanisms underlying pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease, with approximately 10% of cases associated with genetic variants. Recent genetic studies have reported pathogenic variants in the TBX4 gene in patients with PAH, especially in patients with childhood-onset of the disease, but the pathogenesis of PAH caused by TBX4 variant has not been fully uncovered. METHODS: We analysed the TBX4 gene in 75 Japanese patients with sporadic or familial PAH using a PCR-based bidirectional sequencing method. Detected variants were evaluated using in silico analyses as well as in vitro analyses including luciferase assay, immunocytochemistry and chromatin immunoprecipitation (ChIP) whether they have altered function. We also analysed the function of TBX4 using mouse embryonic lung explants with inhibition of Tbx4 expression. RESULTS: Putative pathogenic variants were detected in three cases (4.0%). Our in vitro functional analyses revealed that TBX4 directly regulates the transcriptional activity of fibroblast growth factor 10 (FGF10), whereas the identified TBX4 variant proteins failed to activate the FGF10 gene because of disruption of nuclear localisation signal or poor DNA-binding affinity. Furthermore, ex vivo inhibition of Tbx4 resulted in insufficiency of lung morphogenesis along with specific downregulation of Tie2 and Kruppel-like factor 4 expression. CONCLUSION: Our results implicate variants in TBX4 as a genetic cause of PAH in a subset of the Japanese population. Variants in TBX4 may lead to PAH through insufficient lung morphogenesis by disrupting the TBX4-mediated direct regulation of FGF10 signalling and pulmonary vascular endothelial dysfunction involving PAH-related molecules.

A nationwide analysis of renal and patient outcomes for adults with lupus nephritis in Japan.

BACKGROUND: The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan. METHODS: We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study. RESULTS: The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death. CONCLUSION: Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death.

Successful Treatment with Belimumab in a Patient with Refractory Systemic Lupus Erythematosus after Initiation of Hemodialysis: Considering the Synergistic Effect of Belimumab and Immunological Burn-Out Phenomenon in End-Stage Renal Disease Patients on Hemodialysis.

BACKGROUND: In patients with systemic lupus erythematosus (SLE), disease activity can persist even after initiating dialysis. However, guidelines for the treatment of patients with SLE after dialysis is initiated have not yet been established. CASE PRESENTATION: We describe the case of a 54-year-old Japanese woman who was diagnosed with SLE at age 12, progressed to end-stage renal disease (ESRD), and initiated hemodialysis for lupus nephritis. However, SLE activity persisted after hemodialysis. Cyclophosphamide and mycophenolate mofetil were administered in addition to prednisolone and immunoadsorption, but this treatment strategy was limited by side effects. The patient was subsequently treated with belimumab, and the activity of SLE decreased rapidly. CONCLUSIONS: ESRD patients with SLE show no significant decrease in transitional B cells and have elevated levels of B-cell activating factor (BAFF). Both transitional B cells and BAFF are important therapeutic targets for belimumab, indicating that patients with ESRD may benefit from belimumab therapy. However, the effects of belimumab may be potentiated in patients with uremia, who may be more susceptible to adverse events such as infections. Patients with SLE who receive belimumab after initiation of hemodialysis therefore require careful follow-up. Here, we report the first case of belimumab administration in a patient with SLE after initiation of hemodialysis.

First case of a renal cyst infection caused by Desulfovibrio: a case report and literature review.

BACKGROUND: Genus Desulfovibrio species is a sulphate-reducing anaerobic gram-negative rod that resides in the human oral cavity and intestinal tract. It was reported as the causative pathogen of bacteraemia and abdominal infections, but not renal cyst infection, and Desulfovibrio fairfieldensis has higher pathogenicity than other Desulfovibrio species. CASE PRESENTATION: A 63-year-old man was on haemodialysis for end-stage renal failure due to autosomal dominant polycystic kidney disease. On admission, he had a persistent high-grade fever, right lumbar back pain, and elevated C-reactive protein levels. His blood and urine cultures were negative. He received ciprofloxacin and meropenem; however, there was no clinical improvement. Contrast-enhanced computed tomography and plain magnetic resonance imaging revealed a haemorrhagic cyst at the upper pole of the right kidney. The lesion was drained. Although the drainage fluid culture was negative, D. fairfieldensis was detected in a renal cyst using a polymerase chain reaction. After the renal cyst drainage, he was treated with oral metronidazole and improved without any relapse. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a renal cyst infection with Desulfovibrio species. D. fairfieldensis is difficult to detect, and polymerase chain reaction tests can detect this bacterium and ensure better management for a successful recovery.

Impact of school closure due to the coronavirus disease 2019 pandemic on body mass index in Japanese children: Retrospective longitudinal study.

AIM: During the coronavirus disease 2019 pandemic, the governments of many countries responded to high levels of infection with lockdowns. As a result, some children were reported to experience weight gain. The aim of the present study was to examine the impact of school closures on body mass index (BMI) in Japanese children. METHODS: This was a retrospective study of students enrolled in the participating schools (6- to 11-year-old elementary school students and 12- to 14-year-old junior high school students) between 2015 and 2020. Using school health check-up data, annual changes in the BMI standard deviation score (ΔBMI-SDS) were calculated. We compared ΔBMI-SDS in 2019-2020 with the corresponding control years. RESULTS: 19 565 children with complete data were included in the analysis. Median ΔBMI-SDS in 2019-2020 were 0.24-0.35 in elementary school boys, 0.10-0.13 in junior high school boys, -0.02 to 0.15 in elementary school girls and -0.14 to -0.10 in junior high school girls. In comparison with every control year, ΔBMI-SDS in 2019-2020 were significantly higher in elementary school boys (control years: -0.07 to 0.14) and junior high school boys (control years: -0.04 to 0.06), and significantly lower in junior high school girls (control years: -0.06 to 0.09). CONCLUSION: BMI-SDS increased significantly in elementary and junior high school boys, but decreased significantly in junior high school girls. The pandemic appears to have had an impact on Japanese children that was different from other countries.

Inositol 1,4,5-trisphosphate receptor 2 as a novel marker of vasculature to delineate processes of cardiopulmonary development.

Congenital heart diseases (CHDs) involving the outflow tract (OFT), such as persistent truncus arteriosus (PTA), lead to mortality and morbidity with implications not only in the heart, but also in the pulmonary vasculature. The mechanisms of pulmonary artery (PA) development and the etiologies underlying PA disorders associated with CHD remain poorly understood partly because of a specific marker for PA development is nonexistent. The three subtypes of inositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) are intracellular Ca2+ channels that are essential for many tissues and organs. We discovered that IP3R2 was expressed in the vasculature and heart during development using transgenic mice, in which a LacZ marker gene was knocked into the IP3R2 locus. Whole-mount and section LacZ staining showed that IP3R2-LacZ-positive cells were detectable exclusively in the smooth muscle cells, or tunica media, of PA, merging into αSMA-positive cells during development. Furthermore, our analyses suggested that IP3R2-LacZ positive PA smooth muscle layers gradually elongate from the central PA to the peripheral PAs from E13.5 to E18.5, supporting the distal angiogenesis theory for the development of PA, whereas IP3R2-LacZ was rarely expressed in smooth muscle cells in the pulmonary trunk. Crossing IP3R-LacZ mice with mice hypomorphic for Tbx1 alleles revealed that PTA of Tbx1 mutants may result from agenesis or hypoplasia of the pulmonary trunk; thus, the left and right central to peripheral PAs connect directly to the dorsal side of the truncus arteriosus in these mutants. Additionally, we found hypercellular interstitial mesenchyme and delayed maturation of the lung endoderm in the Tbx1 mutant lungs. Our study identifies IP3R2 as a novel marker for clear visualization of PA during development and can be utilized for studying cardiopulmonary development and disease.

Intracellular trafficking pathway of albumin in glomerular epithelial cells.

The intracellular trafficking pathway of albumin in podocytes remains controversial. We therefore analysed albumin endocytosis through caveolae, subsequent transcytosis, and exocytosis. In Western blot and immunofluorescence analysis in vitro, methyl-beta-cyclodextrin (MBCD) treatment significantly decreased the expression of caveolin-1 and albumin in cultured human podocytes after incubation with albumin; additionally, MBCD interfered with albumin endocytosis through caveolae in the experiment using Transwell plates. In the immunofluorescence analysis, albumin was incubated with cultured human podocytes, and colocalisation analysis with organelles and cytoskeletons in the podocytes showed that albumin particles colocalised with caveolin-1 and Fc-receptor but not clathrin in endocytosis, colocalised with actin cytoskeleton but not microtubules in transcytosis, and colocalised with early endosomes and lysosomes but not proteasome, endoplasmic reticulum, or Golgi apparatus. In the electron microscopic analysis of podocytes in nephrotic syndrome model mice, gold-labelled albumin was shown as endocytosis, transcytosis, and exocytosis with caveolae. These results indicate the intracellular trafficking of albumin through podocytes. Albumin enters through caveolae with the Fc-receptor, moves along actin, and reaches the early endosome, where some of them are sorted for lysosomal degradation, and others are directly transported outside the cells through exocytosis. This intracellular pathway may be a new aetiological hypothesis for albuminuria.

Long-term follow-up characteristics of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) receiving chronic hemodialysis at a single center.

BACKGROUND: The clinical characteristics and treatment of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after initiating chronic hemodialysis remain unknown. METHODS: We retrospectively enrolled 11 adult patients with AAV receiving chronic hemodialysis in our hospital from 2000-2016. We collected data describing each patient's clinical findings and treatment before and after initiating hemodialysis. Patients with AAV with and without post-hemodialysis AAV relapse were compared statistically. RESULTS: The average observation period was 6.8 ± 4.1 years, and the interval between diagnosis and initiating chronic hemodialysis was 1.9 ± 2.6 years. Before initiating chronic hemodialysis, five patients (45%) experienced 12 AAV relapses, with diagnoses made serologically or symptomatically. After initiating chronic hemodialysis, four patients experienced nine relapses, with no significant difference between the number of relapses and the number of patients experiencing relapse (p = 0.067 and 0.083, respectively). For patients' entire clinical courses before initiating chronic hemodialysis, the average steroid dose was 11.6 ± 6.9 g/y. Comparing before and after initiating chronic hemodialysis, the steroid dose decreased significantly to 3.3 ± 1.4 g/y after initiating chronic hemodialysis (p = 0.0012). Two of 11 patients died of serious infections after initiating chronic hemodialysis. CONCLUSIONS: Our results showed that the number of relapses tended to be lower despite a significantly different lower amount of steroid after initiating hemodialysis compared with before initiating hemodialysis, and the burn-out phenomenon specific to uremic patients was inferred. We believe that early tapering of steroids should be considered to avoid death rather than focusing only on relapse.

Sertraline Reduces Albuminuria by Interfering with Caveolae-Mediated Endocytosis through Glomerular Endothelial and Epithelial Cells.

INTRODUCTION: Previously, we reported the caveolae-mediated intracellular trafficking pathway of albumin through glomerular endothelial cells (GEnCs) as a new etiological hypothesis of urinary albumin excretion. The selective serotonin reuptake inhibitor, sertraline (Ser), inhibits dynamin, which plays a pivotal role in the fission of caveolae from the cell membrane during caveolae endocytosis. OBJECTIVE: In this study, we evaluated whether Ser reduces albuminuria levels by interfering with albumin endocytosis through caveolae into GEnCs and podocytes as a novel treatment for glomerulonephritis. METHODS: After treating the cells with Ser, albumin and caveolin-1 (Cav-1) expression levels were evaluated by immunofluorescence (IF) and western blot (WB) analyses. The albuminuria level was determined by histology in a puromycin aminonucleoside (PAN)-induced nephrotic syndrome mouse model (PAN mice) treated with or without Ser. RESULTS: IF and WB analyses showed that the albumin expression level was significantly decreased by Ser treatment; however, Cav-1 expression was not decreased in GEnCs or podocytes based on the IF results. In PAN mice treated with or without Ser, Cav-1 expression increased, and the foot process effacement of podocytes and swelling of GEnCs were observed. However, proteinuria levels were not increased in PAN mice treated with Ser relative to that in normal control mice (p = 0.17), and a significant increase was observed in PAN mice without Ser treatment (p = 0.0027). CONCLUSIONS: Ser interfered with albumin internalization through the caveolae into GEnCs and podocytes and reduced albuminuria. Dynamin inhibitors may serve as a novel therapeutic option for reducing albuminuria in glomerulonephritis.

Fate of full-house immunofluorescence staining in renal allograft: A case report.

Here, we report the case of a patient with renal allograft with full-house immunofluorescence staining in the zero-hour biopsy. Full-house immunofluorescence staining is a well-known characteristic of lupus nephritis. Previous studies have reported patients with full-house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full-house nephropathy. We identified only one case out of 2203 zero-hour biopsies over 13 years. Zero-hour biopsy presented no glomerular changes but showed full-house immunofluorescence staining. Electron microscopy revealed a nonorganized electron-dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)-associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1-3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.

Type 2 inositol 1,4,5-trisphosphate receptor inhibits the progression of pulmonary arterial hypertension via calcium signaling and apoptosis.

Pulmonary arterial hypertension (PAH) is a progressive disease associated with vasoconstriction and remodeling. Intracellular Ca2+ signaling regulates the contraction of pulmonary arteries and the proliferation of pulmonary arterial smooth muscle cells (PASMCs); however, it is not clear which molecules related to Ca2+ signaling contribute to the progression of PAH. In this study, we found the specific expression of type 2 inositol 1,4,5-trisphosphate receptor (IP3R2), which is an intracellular Ca2+ release channel, on the sarco/endoplasmic reticulum in mouse PASMCs, and demonstrated its inhibitory role in the progression of PAH using a chronic hypoxia-induced PAH mouse model. After chronic hypoxia exposure, IP3R2-/- mice exhibited the significant aggravation of PAH, as determined by echocardiography and right ventricular hypertrophy, with significantly greater medial wall thickness by immunohistochemistry than that of wild-type mice. In IP3R2-/- murine PASMCs with chronic hypoxia, a TUNEL assay revealed the significant suppression of apoptosis, whereas there was no significant change in proliferation. Thapsigargin-induced store-operated Ca2+ entry (SOCE) was significantly enhanced in IP3R2-/- PASMCs in both normoxia and hypoxia based on in vitro fluorescent Ca2+ imaging. Furthermore, the enhancement of SOCE in IP3R2-/- PASMCs was remarkably suppressed by the addition of DPB162-AE, an inhibitor of the stromal-interacting molecule (STIM)-Orai complex which is about 100 times more potent than 2-APB. Our results indicate that IP3R2 may inhibit the progression of PAH by promoting apoptosis and inhibiting SOCE via the STIM-Orai pathway in PASMCs. These findings suggest a previously undetermined role of IP3R in the development of PAH and may contribute to the development of targeted therapies.

Association of aortic root dilatation with left ventricular function in patients with postoperative ventricular septal defect.

Proximal aortic enlargement is associated with an increased risk of heart failure and all-cause mortality. Recently, aortic root dilatation (ARD) was reported in postoperative patients with ventricular septal defects (VSDs). However, the impact of ARD on left ventricular (LV) function in postoperative VSD patients remains unclear. Thus, the aim of this study was to investigate the effect of ARD on LV function in patients with postoperative VSD. One hundred and thirty-five patients (> 15 years of age) with surgically repaired isolated ventricular defects and who underwent transthoracic echocardiography in our institution between 2009 and 2013 were identified. ARD was defined as an observed aortic root diameter/body surface area > 2.1 cm/m2. The propensity score estimating the probability of having ARD adjusted for anatomical and clinical characteristics was calculated. Forty-four patients (32.6%) had ARD. In unadjusted analyses, right ventricular systolic pressure, Tei index, and E/e' were significantly (p < 0.05) higher in patients with ARD than in those without ARD (31.3 ± 7.5 vs. 35.4 ± 13.7 mmHg, 0.32 ± 0.10 vs. 0.44 ± 0.15, and 7.1 ± 1.7 vs. 9.5 ± 2.9, respectively). In the propensity score-adjusted analysis, significant differences in the Tei index and E/e' were confirmed between the two groups (Tei index difference: 0.11, 95% confidence interval 0.05-0.17; E/e' difference: 2.4, 95% confidence interval 1.3-3.5). However, there were no differences in the other echocardiographic measurements. The presence of ARD in patients with postoperative VSD was significantly associated with LV diastolic dysfunction. Thus, surgically repaired VSD patients require careful screening for aortic enlargement and LV function.

Correction to: Characteristics of membranoproliferative glomerulonephritis based on a new classification at a single center.

In the Original publication, the authors found few errors in the text.

Characteristics of membranoproliferative glomerulonephritis based on a new classification at a single center.

BACKGROUND: Recently, a new classification has been established for membranoproliferative glomerulonephritis (MPGN). However, the effect of the new classification on MPGN treatment is not fully understood. METHODS: We conducted a retrospective study of 87 patients with biopsies diagnosed as MPGN. We reclassified 87 MPGN patients diagnosed between 1977 and 2014 at our hospital, according to the new classification, and analyzed both primary immune complex (IC)- and Alternative pathway (AP)-mediated MPGN [corrected] in terms of clinicopathological features, treatment, and renal prognosis. RESULTS: Proteinuria was abundant in the IC-mediated MPGN group (p = 0.0063), and the serum albumin level was significantly lower in the IC-mediated MPGN group (p = 0.0186). The serum C3 value was significantly lower in the CP-mediated MPGN group (p = 0.0317). Serum CH50 values were also lower in the CP-mediated MPGN group (p = 0.0404). However, glomerular deposition of C3 showed no significant differences in immunofluorescence findings. The 148.6-month renal survival rate was similar in both groups (p = 0.445). CONCLUSION: These results suggested no significant differences in complement activation of the solid phase in local glomeruli and therefore equivalent in renal prognosis [corrected].

Successful treatment with rituximab of immunotactoid glomerulopathy exhibiting nephrotic syndrome
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As immunotactoid glomerulopathy (ITG) is a very rare primary glomerular disease, no standard treatment has been established. It has been reported that ITG progresses to end-stage renal disease at a high rate. Here, we report a case of ITG exhibiting nephrotic syndrome treated by administration of a single dose of rituximab every 6 months for 4 years. In this case, complete remission (CR) was not achieved with steroids alone, but was achieved through long-term depletion of B cells by administration of rituximab. This is the first report that single-dose rituximab every 6 months for 4 years not only achieved CR of ITG, but also allowed steroid tapering.
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