Chronic kidney disease and clinical outcomes in patients with COVID-19 in Japan

Clinical and Experimental Nephrology - Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to...     

The essence of the Japan Radiological Society/Japanese College of Radiology Imaging Guideline

Diagnostic imaging is undoubtedly important in modern medicine, and final clinical decisions are often made based on it. Fortunately, Japan has the highest numbers of diagnostic imaging instruments, such as CT and MRI devices, and boasts easy access to them as well as a high level of diagnostic accuracy. In consequence, a very large number of imaging examinations are performed, but diagnostic instruments are installed in so many medical facilities that expert management of these examinations tends to be insufficient. Particularly, in order to avoid risks, clinicians have recently become indifferent to indications of imaging modalities and tend to rely on CT or MRI resulting in increasing the number of imaging examinations in Japan. This is a serious problem from the viewpoints of avoidance of unnecessary exposure and medical economy. Under these circumstances, the Japan Radiological Society and Japanese College of Radiology jointly initiated the preparation of new guidelines for diagnostic imaging. However, the field of diagnostic imaging is extremely wide, and it is impossible to cover all diseases. Therefore, in drafting the guidelines, we selected important diseases and focused on “showing evidence and suggestions in the form of clinical questions (CQs)” concerning clinically encountered questions and “describing routine imaging techniques presently considered to be standards to guarantee the quality of imaging examinations”. In so doing, we adhered to the basic principles of assuming the readers to be “radiologists specializing in diagnostic imaging”, “simultaneously respecting the global standards and attending to the situation in Japan”, and “making the guidelines consistent with those of other scientific societies related to imaging”. As a result, the guidelines became the largest ever, consisting of 152 CQs, nine areas of imaging techniques, and seven reviews, but no other guidelines in the world summarize problems concerning diagnostic imaging in the form of CQs. In this sense, the guidelines are considered to reflect the abilities of diagnostic radiologists in Japan. The contents of the guidelines are essential knowledge for radiologists, but we believe that they are also of use to general clinicians and clinical radiological technicians. While the number and contents of CQs are still insufficient, and while chapters such as those on imaging in children and emergency imaging need to be supplemented, the guidelines will be serially improved through future revisions. Lastly, we would like to extend our sincere thanks to the 153 members of the drafting committee who authored the guidelines, 12 committee chairpersons who coordinated their efforts, six members of the secretariat, and affiliates of related scientific societies who performed external evaluation.     

Differences in vertebral,tibial, and iliac cancellous bone metabolism in ovariectomized rats

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3–0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.     

The effect of <Emphasis Type="Italic">Clostridium butyricum</Emphasis> MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis

Purpose

Ulcerative colitis (UC) is a chronic, relapsing, and refractory disorder of the intestine. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the preferred and standard surgical procedure for patients’ refractory to medical therapy. Pouchitis is one of the most common long-term complications after IPAA. In the present study, the safety and efficacy of Clostridium butyricum MIYAIRI (CBM) as a probiotic were examined.

Methods

A randomized and placebo-controlled study was performed. Seventeen patients were recruited from 2007 to 2013. Nine tablets of MIYA-BM^® or placebo were orally administered once daily. The cumulative pouchitis-free survival, pouch condition (using the modified pouch disease activity index), and blood parameters were evaluated. A fecal sample analysis was also performed.

Results

Subjects were randomly allocated to receive MIYA-BM or placebo (9 and 8 subjects, respectively). One subject in the MIYA-BM group and four subjects in the placebo group developed pouchitis. No side effects occurred in either group. Characteristic intestinal flora was observed in each group.

Conclusions

Our results suggest that probiotic therapy with CBM achieved favorable results with minimal side effects and might be a useful complementary therapy for the prevention of pouchitis in patients with UC who have undergone IPAA.

     

Clinical features of patients with pars defects identified in adulthood

Purpose

Lumbar spondylolysis is considered a stress fracture of the pars interarticularis that occurs during growth. However, it is sometimes insidious and identified in adults as pseudoarthrosis, the terminal-stage of spondylolysis. The purpose of this study was to identify the clinical features of patients with terminal-stage spondylolysis that first manifested during adulthood.

Patients and methods

Thirty-six patients (21 men, 15 women; mean age 55.8 years; age range 25–77 years) with low back pain (LBP) were studied. In all patients, lumbar spondylolysis had not been diagnosed until the first visit to our hospital. Patient data collected were history of athletic activity and LBP during their growth period and radiological findings, such as spinal level, displacement, and spina bifida occulta (SBO).

Results

Among the 36 patients, including a patient with multi-level spondylolysis (L4 and L5), a total of 37 vertebrae with terminal-stage spondylolysis were identified. Twenty-three (89.2 %) of the 37 vertebrae had L5 spondylolysis. Sixteen patients (44.4 %) had no history of athletic activity, 26 (72.2 %) had no experience of LBP during their growth period, and 14 (38.9 %) had neither. Twenty of the 37 vertebrae (70.4 %) involved displacement (grade 1 = 14; grade 2 = 6). In nine patients (25.0 %; eight men, one woman), SBO of the sacrum was accompanied by L5 spondylolysis.

Conclusions

Approximately 90 % of patients with terminal-stage spondylolysis that was first diagnosed in adulthood involved the L5. Also, about 40 % had no history of athletic activity or experience of LBP during their growth period. In addition, only some patients with L5 spondylolysis had SBO, and all but one of these patients was male. This suggests that male patients with L5 spondylolysis may have some congenital predisposition.

     

Hypoxia augments MHC class I antigen presentation via facilitation of ERO1‐α‐mediated oxidative folding in murine tumor cells

To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer‐specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here, we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen‐specific CTLs by tumor cells that had been pre‐incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre‐incubated under a condition of normoxia. Cell surface expression of MHC class I‐peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs. We show that the hypoxia‐inducible ER‐resident oxidase ERO1‐α plays an important role in the hypoxia‐induced augmentation of MHC class I‐peptide complex expression. ERO1‐α facilitated oxidative folding of MHC class I heavy chains, thereby resulting in the augmentation of cell surface expression of MHC class I‐peptide complex under hypoxic conditions. These results suggest that since the expression of MHC class I‐peptide complex is augmented in a hypoxic tumor microenvironment, strategies for inhibiting the function of regulatory T cells and myeloid‐derived suppressor cells and/or immunotherapy with immune checkpoint inhibitors are promising for improving cancer immunotherapy.     

Simple and rapid detection of the porcine reproductive and respiratory syndrome virus from pig whole blood using filter paper

The combination of Flinders Technology Associates filter papers (FTA cards) and real-time PCR was examined to establish a simple and rapid technique for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) from whole pig blood. A modified live PRRS vaccine was diluted with either sterilised saline or pig whole blood, and the suspensions were applied onto the FTA cards. The real-time RT-PCR detection of PRRSV was performed directly with the samples applied to the FTA card without the RNA extraction step. Six whole blood samples from at random selected piglets in the PRRSV infected farm were also assayed in this study. The expected PCR product was successfully amplified from either saline diluted or pig whole blood diluted vaccine. The same PCR ampliocon was detected from all blood samples assayed in this study. This study suggested that the combination of an FTA card and real-time PCR is a rapid and easy technique for the detection of PRRSV. This technique can remarkably shorten the time required for PRRSV detection from whole blood and makes the procedure much easier.     

Independent evolution of pyrimethamine resistance in Plasmodium falciparum isolates in Melanesia

Pyrimethamine resistance in Plasmodium falciparum has previously been shown to have emerged once in Southeast Asia, from where it spread to Africa. Pyrimethamine resistance in this parasite is known to be conferred by mutations in the gene encoding dihydrofolate reductase (dhfr). We have analyzed polymorphisms in dhfr as well as microsatellite haplotypes flanking this gene in a total of 285 isolates from different regions of Melanesia (Papua New Guinea, Vanuatu, and the Solomon Islands) and Southeast Asia (Thailand and Cambodia). Nearly all isolates (92%) in Melanesia were shown to carry a dhfr double mutation (CNRNI [underlining indicates the mutation]) at positions 50, 51, 59, 108, and 164, whereas 98% of Southeast Asian isolates were either triple (CIRNI) or quadruple (CIRNL) mutants. Microsatellite analysis revealed two distinct lineages of dhfr double mutants in Melanesia. One lineage had the same microsatellite haplotype as that previously reported for Southeast Asia and Africa, suggesting the spread of this allele to Melanesia from Southeast Asia. The other lineage had a unique, previously undescribed microsatellite haplotype, indicative of the de novo emergence of pyrimethamine resistance in Melanesia.     

Salivary duct carcinoma in the mandible: a case report

Salivary duct carcinoma (SDC) is a distinctive and aggressive neoplasm. The most frequent site of origin is the parotid gland, followed by the submandibular gland. SDC originating in the minor salivary glands, particularly in the ectopic glands within the mandible, is extremely rare. We describe a 62-year-old man with SDC in the mandible, who presented with a painless lump in the right submandibular region (later identified as lymph node metastasis) and ipsilateral mental nerve palsy. Histologic examination after ablative surgery revealed SDC originating in the mandible and cervical nodal metastases spreading to levels I-III. The patient remains alive 59 months after presentation as a result of postoperative full-dose irradiation and regular intensive chemotherapy using TXT, 5-FU, and CDDP. However, the patient has local recurrence and distant metastases to the lung and brain. In this report, we also discuss the specific diagnostic criteria and developmental theories of intraosseous salivary gland tumors.     

Changing Blue Fluorescent Protein to Green Fluorescent Protein Using Chemical RNA Editing as a Novel Strategy in Genetic Restoration

Using the transition from cytosine of BFP (blue fluorescent protein) gene to uridine of GFP (green fluorescent protein) gene at position 199 as a model, we successfully controlled photochemical RNA editing to effect site‐directed deamination of cytidine (C) to uridine (U). Oligodeoxynucleotides (ODNs) containing 5′‐carboxyvinyl‐2′‐deoxyuridine (^CVU) were used for reversible photoligation, and single‐stranded 100‐nt BFP DNA and in vitro‐transcribed full‐length BFP mRNA were the targets. Photo‐cross‐linking with the responsive ODNs was performed using UV (366 nm) irradiation, which was followed by heat treatment, and the cross‐linked nucleotide was cleaved through photosplitting (UV, 312 nm). The products were analyzed using restriction fragment length polymorphism (RFLP) and fluorescence measurements. Western blotting and fluorescence‐analysis results revealed that in vitro‐translated proteins were synthesized from mRNAs after site‐directed RNA editing. We detected substantial amounts of the target‐base‐substituted fragment using RFLP and observed highly reproducible spectra of the transition‐GFP signal using fluorescence spectroscopy, which indicated protein stability. ODNc restored approximately 10% of the C‐to‐U transition. Thus, we successfully used non‐enzymatic site‐directed deamination for genetic restoration in vitro. In the near future, in vivo studies that include cultured cells and model animals will be conducted to treat genetic disorders.