During this half a century since immunoglobulin A (IgA) nephropathy was firstly reported in 1968, several clinical and histological grading systems to predict the prognosis have been reported. In Japan, since the first version of clinical guideline for IgA nephropathy was established in 1995, it was revised in 2014 to the third version which was the grading system based on both clinical and histological risk factors. In this report, we have shown the details and evaluation of clinical grading system of that Japanese guideline, and also shown the previous reported clinical grading system.

This report is secondary publication of previous our review report "Nippon Rinsho 77: 643-650, 2019".

Background: Evidence-based return-to-work (RTW) guidelines are lacking in Japan. Here, we investigated whether workplace interventions would shorten the sick-leave period.

Methods: A literature search using six occupational health review questions (OHRQs) was conducted in January 2016, and randomized controlled trials were selected. A meta-analysis was conducted for OHRQs 1 and 2 and a qualitative systematic review for OHRQs 3 and 4. Recommendations were subsequently made after thoroughly considering their feasibility in Japan.

Results: A committee formed by the Kanto Branch of the Japan Society for Occupational Health agreed on four recommendations for employees concerning sick-leave due to musculoskeletal and mental health disorders.

Conclusion: Conditional recommendations included that RTW programs (OHRQ1) and collaboration between occupational health and clinical staff (OHRQ2) shorten the length of sick-leave due to musculoskeletal and mental health disorders. Work accommodation (OHRQ4) was also conditionally recommended for musculoskeletal disorders. Social support was also a good practice approach despite insufficient evidence.

Background: Hand tremors during surgery requiring precise techniques increase procedure durations and adversely affect outcomes. Most of the currently available devices used to reduce tremors during surgery are large, heavy, and expensive. This study aimed to develop and evaluate an easily movable hand support device to improve surgical outcomes.

Methods: We designed and developed a new device comprising a hand support bar and foot switch. The utility of the device was experimentally evaluated by 11 neurosurgeons with a mean experience of 6.7 (range: 0-13) years. A patient model simulating puncture techniques of suture needles in superficial and deep cerebral vessels during brain surgery was created, and the accuracy of targeting puncture sites and the time required for puncture were measured.

Results: The use of the newly developed hand support device resulted in a significant improvement in the accuracy of targeting puncture site in both, superficial (p < 0.0001) and deep (p = 0.0041) surgery conditions and reduced the time required to puncture both, superficial (p=0.0006) and deep (p=0.0527) targets compared to non-use of the hand support device.

Conclusion: The newly developed hand support device has the potential to improve microsurgery outcomes by stabilizing hand tremors and reducing procedure duration.

Background: Dysphagia is the important complication related to cerebral small vessel disease (CSVD) including lacunar infarcts (LIs), white matter hyperintensity (WMH), cerebral microbleeds (CMBs) and perivascular spaces (PVS). The aim of this study was to investigate the relationship between swallowing function and CSVD.

Methods: This study is based on the authors' prospective registry between 2015 and 2017. We enrolled 352 patients and signs of CSVD on magnetic resonance imaging (MRI). Swallowing function was evaluated using the Repetitive Saliva Swallowing Test and the Modified Water Swallow Test. On MRI, the severity of WMH including deep WMH (DWMH), the number of LIs, CMBs and PVS were assessed.

Results: Seventy-nine out of 352 (24.4%) patients exhibited swallowing impairment. Mean age was 70.4±10.6 years and 218 were male (63.4%). Those with dysphagia had higher WMH scores and a greater number of LIs than those without. The severity of whole WMH, frontal and parietal DWMH were associated with dysphagia. After adjustment for age, sex, vascular risk factors, and Mini Mental State Examination, whole WMH severity still associated with dysphagia.

Conclusions: WMH, particularly frontal and parietal DWMH, was associated with swallowing impairment.

Background: Childhood obesity has been suggested as a risk factor for bronchial asthma. The aim of this study was to clarify the relationship between clinical factors related to obesity, including adipocytokines and eosinophilic inflammation, as candidate pathogenesis mechanisms of bronchial asthma in Japanese children and adolescents.

Methods: Forty-one children and adolescents visiting our outpatient clinic were enrolled. The relationship between participants' clinical and demographic characteristics and fraction of exhaled nitric oxide (FENO) or blood eosinophil (B-Eos) count values were analyzed.

Results: No significant correlation was observed between either FENO or B-Eos count values and the body mass index z-score. FENO was high (≥35 ppb) in 8 cases and normal (<35 ppb) in 33 cases. Adiponectin was significantly lower in the high FENO group than in the normal FENO group (6.5 vs. 8.1 μg/mL, p<0.02). A negative correlation between B-Eos count values and adiponectin levels (r=−0.34, p<0.05) and a positive correlation between B-Eos count values and plasminogen activator inhibitor-1 levels were noted (r=0.42, p<0.01). The univariable odds ratio of adiponectin for high FENO was 0.62 (0.41-0.95) and the association was borderline after adjusting for B-Eos.

Conclusions: Eosinophilic inflammation was associated with a decrease in serum adiponectin levels which may be induced by visceral fat accumulation.

Background: In neurovascular therapy, normally surgeons directly instruct a radiologist to operate a computer on their behalf to maintain sterility in the operative field when reconfirming medical images. This process, however, takes time and causes psychological burden.

Methods: A touchless interface operated by hand-gestures and voice named "Opect3D" was developed to resolve the above issues. Initially, the Opect3D and conventional verbal communication were compared preclinically. The operation time for deciding the rotation angle and the angular difference against the targeted position were measured and calculated, respectively. Afterwards, Opect3D was utilized in unruptured cerebral aneurysms and the usefulness and psychological burden were surveyed.

Results: The mean time using the verbal communication was 24.1 ± 7.9 sec, while using Opect3D was 12.8 ± 5.3 sec per single interaction (p < 0.01). The angular difference using the verbal communication was 9.0 ± 8.4 degrees and 9.4 ± 6.1 degrees using Opect3D (p = 0.87). The survey of usefulness and psychological burden of using Opect3D yielded 4.03 ± 0.73 (p < 0.02) and 4.67 ± 0.54 (p < 0.01), respectively, as a mean value. Scores ranged from 1 (worst) to 5 (best), with 3 corresponding to the verbal communication. Significance was evaluated from the score of 3.

Conclusions: Usage of Opect3D was effective in reducing operation time and stress, thus enhancing efficiency and ease of operation.

Background: Colorectal cancer (CRC) sidedness is predictive of anti-epidermal growth factor receptor (anti-EGFR) antibody therapy effectiveness; however, the mechanism linking them is unclear. Long interspersed nuclear element-1 (LINE-1) methylation has been associated with sidedness. Here, we evaluated whether LINE-1 expression in CRC cell lines influenced the efficacy of EGFR inhibitors.

Methods: We analyzed LINE-1 methylation in 98 clinical CRC samples. We also treated RAS-wild type SW48 and Caco-2 and RAS-mutant SW480, HCT116, and DLD-1 CRC cell lines with EGFR inhibitors gefitinib or RG14620, and performed growth assays in LINE-1-suppressed Caco-2, SW480, and DLD-1 cells.

Results: Clinical CRC findings confirmed the association between LINE-1 methylation and sidedness. LINE-1 mRNA expression was high in SW480 and Caco-2 cells and low in HCT116 and SW48 cells. The half maximal inhibitory concentrations (IC₅₀) of gefitinib were lower for LINE-1-expressing Caco-2 cells than for non-LINE-1-expressing SW48 cells, revealing an association between LINE-1 expression and the efficacy of gefitinib in RAS-wild type cells. LINE-1 knockdown increased the IC₅₀ of gefitinib in Caco-2 cells. There was trend of increase in RG14620 IC₅₀ upon LINE-1 knockdown even in RAS-mutant SW480 and DLD-1 cells, suggesting other mechanisms of RG14620 than EGFR signal inhibition.

Conclusion: EGFR inhibitor gefitinib requires LINE-1 expression, and interventions targeting LINE-1 may increase its efficacy.

Gestational diabetes mellitus (GDM) is associated with an increased long-term risk of developing diabetes. We investigated the risk factors for early postpartum glucose intolerance in patients with GDM.

A total of 148 patients with GDM were included in this study. Among them, 30 and 118 were diagnosed with GDM before (B20w group) and after (A20w group) 20 weeks of gestation, respectively. Oral glucose tolerance test (OGTT) was performed in all patients 58 days after delivery. In each group, the association between the postpartum OGTT results and the following parameters were analyzed: age, BMI, family history of diabetes, plasma glucose levels in diagnostic prenatal OGTT, number of abnormal OGTT values, glycated hemoglobin and glycated albumin (GA) levels at diagnosis of GDM, serum C-peptide levels, frequency of insulin therapy, and pregnancy outcomes.

Postpartum OGTT revealed glucose intolerance in 9 and 35 patients in the B20w and A20w groups, respectively. In the B20w group, placental weight was an independent predictor for glucose intolerance. In the A20w group, GA level and family history were independent predictors for glucose intolerance.

Elevated GA levels may be associated with a higher risk of postpartum glucose intolerance in patients with GDM diagnosed after 20 weeks of gestation.

Background: Glioblastoma is a highly aggressive primary malignant brain tumor. New treatments, especially ones that can eradicate subpopulations with stem-cell-like properties, are currently being explored. In vitro, epirubicin has demonstrated toxicity towards such populations. However, epirubicin fails to readily cross the blood-brain barrier. Furthermore, its efficacy against stem-like tumor cells growing within the neural tissue has not been fully addressed. Polymeric micelles are an advanced system developed to enhance drug delivery into tumors.

Methods: We have investigated the effect of epirubicin micelles against murine glioma initiating cells (GICs) in vitro and ex vivo.

Results: In vitro, epirubicin micelles inhibited the sphere growth of GICs in a dose-dependent manner. Furthermore, they also inhibited the growth of GIC-based tumors in ex vivo cultured brain slices from the tumor-bearing mice. This effect was inversely proportional to the tumor size at the beginning of the treatment.

Conclusions: Our results suggest that epirubicin micelles are effective against murine glioma cells with stem cell properties and their use should be initiated at an early stage.

In recent years, salmon roe allergies have become common among young children. Conventionally, the diagnosis of a salmon roe allergy has been confirmed by a positive specific immunoglobulin E (IgE) antibody test. We encountered a case of anaphylaxis caused by salmon roe in a child aged 2 years and 10 months. The total amount of IgE antibody was low, thus, the salmon roe-specific IgE antibody test was negative. However, the skin prick test showed positive results, and thus, the diagnosis was confirmed. The skin prick test was found to be useful for confirming an anaphylaxis due to salmon roe in young children with low specific IgE antibody levels.

It is well known that sedation during mechanical ventilation should not be performed beyond the level necessary while being monitoring sedation status. However, some patients only complain of insomnia, even though the patient's degree of sedation has been assessed to be adequate. A woman aged 50 years with a history of systemic lupus erythematosus was transferred into our ICU with a diagnosis of respiratory infection. In 10 days treatment with antibacterial drug and mechanical ventilation improved her respiratory condition well enough to prepare for weaning from mechanical ventilation support. Her sedation was well managed such that a Richmond Agitation-Sedation Scale (RASS) score of −2 to −4 was achieved during treatment. In the process of ventilator weaning involved reducing her sedation gradually, targeting a RASS score of 0 to −1, she then began to complain of severe sleep disturbance. Neither ramelteon nor mianserin administration could improve her insomnia. Multidisciplinary discussion decided a trial of foot-bathing therapy for her sleep disorder. After starting warm footbath care during a daytime, her insomnia improved dramatically in a short time without additional medication or increasing the drug dosage. As the result, her extubation succeeded smoothly without delay.

Lissencephaly is a severe brain malformation associated with abnormal formation of cerebral sulci. Until now, many genes related to lissencephaly have been identified. Among them, classical lissencephaly has been often related to the platelet activating factor acetylhydrolase 1B regulatory subunit 1 gene (PAFAH1B1). We identified a novel PAFAH1B1 splicing variant (NM_000430.3:c.118-2A>G) in a female patient with classical lissencephaly manifesting as developmental delay, growth failure, and epilepsy. This variant was not detected in her parents, indicating de novo occurrence of the variant in the patient. To confirm whether this variant is in fact related to splicing error, RNA expression was analyzed. As suspected, an abnormal short band excluding exon 4 was additionally detected. This evidence confirmed that the novel variant is definitely pathogenic to cause lissencephaly in the patient.

We reported a rare case of low-grade mucoepidermoid carcinoma of the hard palate with bone changes. Preoperative coronal computed tomography was useful to reveal thinning of the palatine bone. We performed the total resection of the tumor including palatine bone with a safety margin of 5 mm or more in monobloc fashion and reconstructed with a palatal mucoperiosteal flap. There is no recurrence and complications for five years after surgery.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC; MIM#604004) is a rare congenital disorder of the cerebral white matter. Most MLC patients have MLC1 mutations which are inherited in an autosomal recessive manner. Since there is no established biomarker for MLC, genetic testing is necessary for a final diagnosis. We identified compound heterozygous mutations in two different Japanese patients having MLC. Both patients showed a common mutation of c.278C>T (p.Ser93Leu) in a heterozygous status. In addition, two different mutations (c.337_353delinsG and c.423+1G>A) were identified in the homologous alleles of the patients, respectively. Although these two variants were first identified in the Japanese population, they have since been reported in other Asian countries and might be founder mutations of the gene in Asian population.

Cancer of an unknown primary site (CUP) accounts for approximately 3% of all cancer cases. Among these cases, mediastinal lymph node cancer is comparatively rare, and there are no established treatment methods or approaches. Excision of CUP is feasible with the best methods. We herein report a case of mediastinal lymph node CUP resection by robot-assisted thoracoscopic surgery (RATS). The patient was a 60-year-old man. A chest computed tomography (CT) scan identified swelling in the mediastinal lymph node (right tracheobronchial lymph node; #4R) with another organ suspected as the site of the primary lesion, but it was not detected through positron emission tomography (PET). The patient was diagnosed with CUP with lymph node metastasis and mediastinal lymph node dissection was performed via RATS. Histopathological examination revealed desmoplasia in the lymph nodes. Immunohistochemically, the tumor was positive for CK7, TTF1, and napsin A, but negative for CK20, CK5/6, CDX2, p40, and AFP, indicating lung-derived adenocarcinoma. In the narrow space such as the mediastinum, RATS is a useful procedure for resectable mediastinal tumors.

Non-invasive ventilation (NIV) is occasionally used for management of acute respiratory failure in a do-not-intubate (DNI) patient, when conventional oxygen administration or high-flow nasal cannula fail to improve respiratory distress. In such situations, the duration of NIV may be prolonged and cause complications due to the oro-nasal mask. The helmet can be an alternative interface to the oro-nasal mask for improving tolerability and reducing complications. Although the efficacy of helmet NIV has been demonstrated in patients with acute respiratory distress syndrome, the utility of helmet NIV in DNI patients has not been discussed. We present the case of a DNI patient with acute respiratory failure, in which helmet NIV was used instead of the conventional oro-nasal mask. Helmet NIV proved effective in preventing pressure -induced skin complications associated with oro-nasal mask NIV and relieved discomfort in this patient. Furthermore, the patient's communication ability was retained, thereby respecting the wish of the patient and his family.