Recurrent acute kidney injury with Fanconi syndrome related to red yeast rice supplement.

A 51-year-old woman was admitted to our hospital for acute kidney injury (AKI) with an elevated serum creatinine level of 5.07 mg/dL and Fanconi syndrome. The patient was discharged after partial recovery of kidney dysfunction with conservative treatment but was readmitted approximately three months later due to a recurrence of AKI with Fanconi syndrome. A kidney biopsy revealed findings consistent with acute tubular necrosis and localized tubulointerstitial nephritis, with no specific vascular or glomerular lesions. The patient's medical history revealed that prior to both AKI episodes, the patient had been taking "Red Yeast Cholestehelp", a lipid-lowering supplement for a period of time. Her kidney dysfunction and Fanconi syndrome improved with the discontinuation of the supplement and correction with oral medications. In Japan, a series of similar health hazards related to the red yeast rice supplement has been reported, but the causative toxin and its causal relationship with AKI have not been established. The present case provides firm evidence that clinically supports this relationship.

Acute kidney tubular injury after ingestion of red yeast rice supplement.

A 47-year-old woman developed severe kidney dysfunction after taking a lipid-lowering supplement, Red Yeast Rice Cholestehelp, for approximately 7 months. The patient developed sudden nausea and had an elevated serum creatinine level of 4.26 mg/dL. A kidney biopsy showed findings consistent with acute tubular necrosis. Kidney dysfunction improved with discontinuation of supplementation, and corticosteroid therapy. Similar kidney involvement has been reported, raising concerns regarding supplements in Japan. An investigation of the nephrotoxic ingredients in the same product batches is currently underway. This report underscores the need for public awareness and warnings of health risk concerns associated with unregulated supplements.

A retrospective cohort study evaluating the incidence of herpes zoster and postherpetic neuralgia after a live attenuated Oka-strain herpes zoster vaccine in a real-world setting in Japan.

BACKGROUND: In Japan, freeze-dried live attenuated Oka-strain varicella-zoster virus vaccine, VVL (BIKEN), is available for adults aged ≥50 years to prevent herpes zoster (HZ). Although an increase in the antibody titer and cellular immune response has been demonstrated following vaccination with VVL (BIKEN), to date, no clinical studies have shown that the vaccine decreases the incidence of HZ and postherpetic neuralgia (PHN). This study investigated the incidence of HZ and PHN among adults aged ≥50 years who received a single dose of VVL (BIKEN) to prevent HZ. METHODS: This retrospective cohort study investigated the incidence of HZ and PHN among adults aged ≥50 years who received a single dose of VVL (BIKEN) at a large hospital and affiliated clinics in Japan. A dispensing database and electronic medical records were used to identify vaccine recipients and cases of HZ and PHN. The end date of the follow-up period and the reason to end the follow-up were defined to avoid underestimating the incidence. The analysis was stratified according to age, sex, immunocompromising conditions, and use of immunosuppressant therapy. Vaccine effectiveness was estimated using published estimates of the incidence of HZ and PHN in the unvaccinated population in Japan. RESULTS: A total of 1175 patients were enrolled in the study. During a median follow-up period of 3.36 years, HZ was diagnosed in 27 participants (15 men [2.8%] and 12 women [1.9%]). The incidence of HZ among VVL (BIKEN) recipients was 7.67/1000 person-years. The incidence of PHN was 0.82/1000 person-years. The vaccine effectiveness was estimated as 27.8% [95% confidence interval (CI), -29.8 to 63.9%] and 73.8% [95% CI, 38.6-100%] against HZ and PHN, respectively. CONCLUSIONS: The VVL (BIKEN) had limited effectiveness at preventing HZ, but relatively good effectiveness at preventing PHN. VVL (BIKEN) might have a role as an affordable alternative.

Neural epidermal growth factor-like 1 protein (NELL1)-associated membranous nephropathy with heterogeneous underlying diseases: a case report.

Neural epidermal growth factor-like 1 protein (NELL1) is a target antigen of membranous nephropathy (MN). NELL1-associated MN (NELL1-MN) was originally described as a primary form but has subsequently been associated with other diseases, including malignancies, pre-exposure to certain drugs, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and rheumatoid arthritis (RA). We present a case of a 78-year-old woman with long-standing RA who developed persistent proteinuria and was diagnosed with MN. Evaluation of the underlying cause revealed chronic active HCV infection and past HBV infection. The underlying cause was less likely to be drug-related; however, there was no evidence of malignancy. The patient was diagnosed with HCV-associated MN. At 4 years after the diagnosis of MN, the patient died of breast cancer with multiple metastases. Subsequent immunohistological analysis revealed that she had NELL1-MN, and her breast cancer tissue stained positive for NELL1. Our case illustrates the difficulty in establishing the underlying cause of NELL1-MN, even after diagnosis. However, the incidence of malignancies, particularly breast and prostate cancers, is higher in NELL1-MN than in MN with other target antigens. Therefore, malignancies are considered a priority for investigation because of their frequency and prognosis among patients with NELL1-MN.

Blechschmidt Collection: Revisiting specimens from a historical collection of serially sectioned human embryos and fetuses using modern imaging techniques.

Along with the Carnegie Collection in the United States and the Kyoto Collection in Japan, the Blechschmidt Collection (Georg-August-University of Göttingen, Germany) is a major historical human embryo and fetus collection. These collections are of enormous value to human embryology; however, due to the nature of the historical histological specimens, some stains are fading in color, and some glass slides are deteriorating over time. To protect these specimens against such degradation and ensure their future usefulness, we tried to apply modern image scanning and computational reconstruction. Samples of histological specimens of the Blechschmidt Collection were digitized into images using commercial flatbed scanners with a resolution of 4800 pixels per inch. Two specimens were reconstructed into three-dimensional (3D) images by using modern techniques to vertically stack two-dimensional images of the slices into 3D blocks. The larger specimen of crown-rump length (CRL) 64.0 mm, a series of very large histological sections in human embryology, was reconstructed clearly, with its central nervous system segmented before stacking. The smaller specimen of CRL 17.5 mm was also reconstructed into 3D images. The outer surface of the embryo was intact, and its development was classified according to the widely used Carnegie stages (CSs). The CS of the specimen was identified as the later half of CS 20. The invaluable Blechschmidt Collection can be revisited for further research with modern techniques such as digital image scanning and computational 3D reconstruction.

Three-dimensional models of the segmented human fetal brain generated by magnetic resonance imaging.

Recent advances in imaging technology have enabled us to obtain more detailed images of the human fetus in a nondestructive and noninvasive manner. Through detailed images, elaborate three-dimensional (3D) models of the developing brain can be reconstructed. The segmentation of the developing brain has been determined by serial sections. Therefore, in this study, we attempted to develop a 3D model of the fetal brain using magnetic resonance image (MRI). MR images from 19 specimens (11 embryonic specimens and eight fetal specimens from 5.2 to 225 mm in crown rump length) were used to reconstruct 3D models of regionalized developing brains. From this analysis, we succeeded in registering a maximum of nine landmarks on MR images and reconstructing 19 sequential models of the regionalized developing brain. To confirm the validity of the landmarks, we also compared our results with three serial sections from the Kyoto Collection; the same morphological characteristics were observed on both serial sections and MRI. The morphological minutiae could be found on MR images, and regionalized models of the developing brain could be reconstructed. These results will be useful for clinical diagnosis of living fetuses in utero.

Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype.

OBJECTIVES: Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period. METHODS: Magnetic resonance images were obtained from 56 specimens. Mid-sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum. RESULTS: Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively. CONCLUSION: The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype. © 2017 John Wiley & Sons, Ltd.