Repetitive pulsed-wave ultrasound stimulation suppresses neural activity by modulating ambient GABA levels via effects on astrocytes.

Ultrasound is highly biopermeable and can non-invasively penetrate deep into the brain. Stimulation with patterned low-intensity ultrasound can induce sustained inhibition of neural activity in humans and animals, with potential implications for research and therapeutics. Although mechanosensitive channels are involved, the cellular and molecular mechanisms underlying neuromodulation by ultrasound remain unknown. To investigate the mechanism of action of ultrasound stimulation, we studied the effects of two types of patterned ultrasound on synaptic transmission and neural network activity using whole-cell recordings in primary cultured hippocampal cells. Single-shot pulsed-wave (PW) or continuous-wave (CW) ultrasound had no effect on neural activity. By contrast, although repetitive CW stimulation also had no effect, repetitive PW stimulation persistently reduced spontaneous recurrent burst firing. This inhibitory effect was dependent on extrasynaptic-but not synaptic-GABAA receptors, and the effect was abolished under astrocyte-free conditions. Pharmacological activation of astrocytic TRPA1 channels mimicked the effects of ultrasound by increasing the tonic GABAA current induced by ambient GABA. Pharmacological blockade of TRPA1 channels abolished the inhibitory effect of ultrasound. These findings suggest that the repetitive PW low-intensity ultrasound used in our study does not have a direct effect on neural function but instead exerts its sustained neuromodulatory effect through modulation of ambient GABA levels via channels with characteristics of TRPA1, which is expressed in astrocytes.

Associations of self-efficacy and outcome expectancy with adherence to continuous positive airway pressure therapy in Japanese patients with obstructive sleep apnea.

Objective: To examine the associations of self-efficacy and outcome expectancy with adherence to continuous positive airway pressure (CPAP) therapy among Japanese men with obstructive sleep apnea (OSA) using objective adherence data for CPAP therapy. Methods: We conducted a retrospective study of 497 Japanese men with OSA who were receiving CPAP therapy. Good adherence was defined as CPAP use of ≥4 hours per night for ≥70% of nights. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of good adherence to CPAP therapy with self-efficacy and outcome expectancy (measured with the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese). The models were adjusted for age, duration of CPAP therapy, body mass index, apnea-hypopnea index, Epworth Sleepiness Scale score, and comorbidities (diabetes mellitus and hypertension). Results: In total, 53.5% of participants had good adherence to CPAP therapy. The mean CPAP use was 5.18±1.53 hours/night. After adjusting for related factors, we found significant associations of good adherence to CPAP therapy with self-efficacy scores (OR, 1.10; 95% CI, 1.05-1.13; p<0.001) and outcome expectancy scores (OR, 1.10; 95% CI, 1.02-1.15; p=0.007). Conclusions: Our results indicate that self-efficacy and outcome expectancy are associated with good adherence to CPAP therapy among Japanese men with OSA.

Associations of diabetes mellitus and hypertension with adherence to continuous positive airway pressure therapy in male patients with obstructive sleep apnea.

Methods: We conducted a retrospective study among 497 male patients with OSA on CPAP therapy. Participants with pretreatment Apnea-Hypopnea Index (AHI) data based on overnight polysomnographic recordings completed a questionnaire. Adherence data for CPAP therapy were collected using a smart card system. We classified CPAP use of ≥4 hours per night and ≥70% of nights as good adherence; other CPAP use was categorized as poor adherence. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for poor adherence to CPAP therapy in the hypertension and diabetes mellitus groups, compared with the no comorbidity group, adjusting for body mass index, duration of CPAP therapy, AHI, and Epworth Sleepiness Scale score. Results: In the no comorbidity, hypertension, and diabetes mellitus groups, 43.4%, 44.7%, and 56.0%, respectively, had poor adherence to CPAP therapy. Being in the diabetes mellitus group was significantly associated with poor adherence to CPAP therapy (OR=1.86, 95% CI: 1.18-2.92, p=0.007); there was no association for the hypertension group. Conclusion: Our results indicate that comorbidity of diabetes mellitus is associated with poor adherence to CPAP therapy in male patients with OSA.

Ultrasound-guided lung biopsy with coaxial technique: pleural contact length affects the occurrence of pneumothorax after first puncture.

PURPOSE: To assess prebiopsy characteristics influencing the occurrence of pneumothorax after first puncture of ultrasound (US)-guided lung biopsy with coaxial technique. MATERIALS AND METHODS: From January 2007 to September 2018, 180 peripheral lung lesions in 174 patients who underwent B-mode US-guided lung biopsy with coaxial technique at single institution were included in this study. Technical success was defined as the ability to make a diagnosis using the acquired sample with/without an adverse event of pneumothorax. Statistical analyses of prebiopsy characteristics were performed to identify the most important cutpoint and to evaluate the effect on diagnostic accuracy. RESULTS: Of the 180 lesions (mean size, 37 mm ± 26.2; mean pleural contact length, 38.2 mm ± 34.4), technical success rate was 97.2% (175/180 lesions) and diagnostic accuracy rate was 91.6% (165/180 lesions). Pneumothorax occurred immediately after first puncture for seven of 180 lesions. Classification and regression tree analysis and Fisher's exact test showed the proportion of the pneumothorax immediately after first puncture was higher in lesions with pleural contact length less than 9.78 mm (p = 0.002). No significant difference was shown between the pneumothorax and non-pneumothorax after first puncture in technical success and final diagnosis success rate. CONCLUSION: Pleural contact length affects the occurrence of pneumothorax after first puncture of US-guided lung biopsy with coaxial technique.

Syntaxin 1B regulates synaptic GABA release and extracellular GABA concentration, and is associated with temperature-dependent seizures.

De novo heterozygous mutations in the STX1B gene, encoding syntaxin 1B, cause a familial, fever-associated epilepsy syndrome. Syntaxin 1B is an essential component of the pre-synaptic neurotransmitter release machinery as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein that regulates the exocytosis of synaptic vesicles. It is also involved in regulating the functions of the SLC6 family of neurotransmitter transporters that reuptake neurotransmitters, including inhibitory neurotransmitters, such as γ-aminobutyric acid (GABA) and glycine. The purpose of the present study was to elucidate the molecular mechanisms underlying the development of febrile seizures by examining the effects of syntaxin 1B haploinsufficiency on inhibitory synaptic transmission during hyperthermia in a mouse model. Stx1b gene heterozygous knockout (Stx1b+/- ) mice showed increased susceptibility to febrile seizures and drug-induced seizures. In cultured hippocampal neurons, we examined the temperature-dependent properties of neurotransmitter release and reuptake by GABA transporter-1 (GAT-1) at GABAergic neurons using whole-cell patch-clamp recordings. The rate of spontaneous quantal GABA release was reduced in Stx1b+/- mice. The hyperthermic temperature increased the tonic GABAA current in wild-type (WT) synapses, but not in Stx1b+/- synapses. In WT neurons, recurrent bursting activities were reduced in a GABA-dependent manner at hyperthermic temperature; however, this was abolished in Stx1b+/- neurons. The blockade of GAT-1 increased the tonic GABAA current and suppressed recurrent bursting activities in Stx1b+/- neurons at the hyperthermic temperature. These data suggest that functional abnormalities associated with GABA release and reuptake in the pre-synaptic terminals of GABAergic neurons may increase the excitability of the neural circuit with hyperthermia.

Establishment of immunity against Epstein-Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion.

CHARGE syndrome is a rare congenital malformation syndrome which may share symptoms with DiGeorge syndrome. Complete DiGeorge syndrome (cDGS) is a severe form of DiGeorge syndrome, characterized by a CD3+ T-cell count of <50/mm3 due to athymia, and is fatal without immunologic intervention. We performed peripheral blood lymphocyte transfusion (PBLT) from an HLA-identical sibling without pretransplant conditioning in a CHARGE/cDGS patient with a novel CHD7 splice site mutation. Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis, and neither acute nor chronic GVHD was observed. After PBLT, T-cell proliferative response to phytohemagglutinin and concanavalin A recovered, and intractable diarrhea improved. EBV infection, evidenced by a gradual increase in the viral genome copy number to a maximum of 2861 copies/µgDNA on day 42 after PBLT, resolved spontaneously. HLA A2402 restricted, EBV-specific CTLs were detected from peripheral blood on day 148, and EBV seroconversion was observed on day 181. Thus, EBV-specific immunity was successfully established by PBLT. Our results indicate that PBLT is a simple and effective therapy to reconstitute immune systems in CHARGE/DiGeorge syndrome.

Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019.

In January 2019, two influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic subunit (PA), which confers reduced susceptibility to baloxavir, were detected from epidemiologically unrelated hospitalised children in Japan. The viruses exhibited reduced susceptibility to baloxavir but were susceptible to neuraminidase inhibitors. Only one of the two children had been treated with baloxavir. An epidemiological analysis suggests possible transmission of the PA I38T mutant A(H3N2) virus among humans.

[A Case of Extrahepatic Bile Duct Carcinoid Tumor Involving Diagnostic Difficulties].

A patient in his 60s had undergone laparoscopic anterior resection for the treatment of carcinoma of the rectum in February 2016. Histopathologic examination revealed the lesion as a pT2(MP)n(-)M0, fStage Ⅰrectal cancer. One year post-surgery, contrast-enhanced computed tomography(CT)revealed enhancement of parts of the intrapancreatic distal bile ducts. Magnetic resonance cholangiopancreatography(MRCP)showed filling defects at the same site. Magnetic resonance imaging( MRI)with an endorectal coil(ERC)was then performed to identify reproducible bile duct filling defects. Neither cytology nor biopsy yielded any findings that definitely indicated malignancy. Intraductal ultrasonography(IDUS)led to the suspicion of a nonepithelial tumor or an enlarged lymph node. Repeated biopsies via ERC were performed based on the absence of evidence of malignancy and revealed the presence of some atypical cells within the lesions. Although no definitive diagnosis could be made, the patient was scheduled for surgery in June 2017 after obtaining his consent. Upon taping of the common bile duct during surgery, a tumor was palpable on the dorsal aspect of the pancreas. The bile duct tumor was completely excised and submitted for intraoperative diagnosis; the pancreatic dorsal aspect appeared to be totally split. There was no evidence of atypia in the neoplasm, which was therefore considered to be benign; however, malignancy could not be completely ruled out because the patient had presented with elevated serum levels of carbohydrate antigen(CA)19-9 once before the operation. After intraoperative consultation with the patient's family members, who were reluctant to provide consent for pancreaticoduodenectomy, we completed the operation with resection of the bile duct tumor, followed by choledochojejunostomy. The tumor was found to be chromogranin A(+), cluster of differentiation(CD)56(+/-), CA19-9(+, solely ductal structure), carcinoembryonic antigen(CEA)(+, solely ductal structure), and intranuclear p53(-), with an MIB- 1 index of<2%. With regard to neuroendocrine markers, a region that could potentially have been a carcinoid tumor, based on the findings on hematoxylin and eosin(HE)staining, and a lumenized superficial region showed positivity in toto. Therefore, the lesion as a whole was diagnosed as a G1 carcinoid neuroendocrine tumor(NET). However, the superficial lumenized layer was positive for both CA19-9 and CEA; therefore, the tumor was thought to concurrently have epithelial characteristics. The lateral stumpwas negative, while the status of the ablated region remained unclear. After discussing the histopathologic examination results with the patient and his family members, the patient's follow-upwas decided to consist of periodic checkups without any further surgical intervention. The patient has since remained free of recurrence. Carcinoid tumor of the bile duct is extremely rare but should be considered in cases involving bile duct tumors that show enhancement on imaging prior to surgery and for which no definitive diagnosis can be established despite repeated biopsy explorations.

Rapidly progressive renal failure due to tubulointerstitial infiltration of peripheral T-cell lymphoma, not otherwise specified accompanied by uveitis: a case report.

BACKGROUND: Rapid decline in renal dysfunction due to primary renal lymphoma, or secondary renal lymphoma by infiltration from a primary origin, is extremely rare. There are notably few reports indicating infiltration of T-cell lymphoma into the kidney. CASE PRESENTATION: A 61-year-old woman with a sudden body rash and liver dysfunction was brought to our hospital presenting with a dull headache and blurred vision. Laboratory tests revealed rapidly progressive renal failure. Histological examination of the kidney and skin indicated infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Infiltration of PTCL-NOS to the liver and spleen, and presence of Uveitis masquerade syndrome were suspected. Imaging showed that the lesion was limited to extralymphatic organs. Renal function was improved with administration of steroids, including pulse steroid therapy, before administering cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. CONCLUSIONS: This is the first reported case of rapidly progressive renal failure caused by perivascular tubulointerstitial nephritis with the direct invasion of PTCL-NOS. In our case, a single steroid dose showed dramatic results with respect to renal symptoms.

Risk of cardiovascular mortality predicted by the serum calcium level and calcification score at the initiation of dialysis.

BACKGROUND: The relationship between serum corrected calcium (CCa) level and vessel calcification at dialysis initiation and survival has seldom been evaluated. Therefore, we evaluated the efficacy of CCa levels and the calcification score at the initiation of dialysis for predicting all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). METHODS: The study group included 407 patients with ESRD, who started hemodialysis between January 2009 and December 2016 at the Red Cross Ishinomaki Hospital. The primary outcomes were the 1- and 3-year all-cause and CV mortality rate, with the association between CCa level and CVD-specific mortality evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. RESULTS: Patients with a high initial CCa level were at higher risk for CVD-related, but not all-cause, mortality than patients with a low initial CCa level [hazard ratio (HR) 2.81; 95% confidence interval 1.05-7.55]. The HR for CVD-related mortality was also higher for patients with an Agatston vessel calcification score > 2000 (HR 13.9; 95% CI 1.63-118.2). Overall, the 3-year CVD-free rate was 88.2% (range 76.4-94.3%). Higher CCa level was associated with a higher Agatston score and cardiac valve calcification. CONCLUSION: High serum CCa levels and an Agatston score > 2000 are independent risk factors of CVD mortality due to advanced vessel calcification.

[A Case of Complete Response to Computed Tomography-Guided Celiac Plexus Neurolysis of Pain Associated with Postoperative Recurrence of Colon Cancer].

The patient was a man in his 40s, who had undergone laparoscopic ileocecal resection with lymph node dissection(D3)for cecal cancer in January 2012. Histopathological examination of the resected specimens had revealed StageⅡ primary tumor with subserosal invasion and positive metastasis in 1-3 regional lymph nodes(pT2[SS]n1[+]). The pathological stage was Ⅲa(fStage Ⅲa), and the tumor showed RAS gene mutation. The patient was administered 5 cycles of postoperative adjuvant chemotherapy with oral tegafur/uracil(UFT)in combination with calcium folinate(UZEL). Abdominal computed tomography( CT)performed 1.5 years postoperatively revealed liver metastasis, and a laparoscopic partial hepatectomy was performed in August 2015. In addition, a node in the greater omentum, located in the inferior surface of the liver, was also resected. Histopathological examination of the resected specimens revealed peritoneal metastasis, based on the identification of the same type of adenocarcinoma as the colon cancer. The patient was given 8 cycles of adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Then, he presented with colonic ileus, caused by recurrent dissemination, and underwent a laparoscopic transverse colectomy in October 2015. Multiple perineal disseminations were found intraoperatively, and chemotherapy was initiated with irinotecan plus tegafur/gimeracil/oteracil(S-1)plus bevacizumab(IRIS/BV)for the recurrent and unresectable disease. After 27 cycles of this regimen, lung metastasis was detected; in addition, progression of the para-aortic node metastasis around the celiac plexus was also observed, and the patient was considered as having pro- gressive disease(PD). Treatment with trifluridine/tipiracil(TAS102)was started in September 2017. Prior to the initiation of this regimen, the dose of opioid rescue medication previously started for back and abdominal pain was rapidly increased. Accordingly, the base dose was increased, but the pain could not be controlled, and the major pain was consistently located along the area of innervation in the celiac plexus. Therefore, celiac plexus neurolysis(CPN)was performed as a local therapy. A CT-guided injection technique was used to administer urografin, bupivacaine, and absolute ethanol to complete the procedure. The patient was discharged without major complications, and the base opioid dose was gradually reduced. Since the patient did not require any rescue medication during daytime on some days, the reduction of the base opioid dose was significantly effective in improving the patient's quality of life(QOL). In patients with pain possibly caused by metastasis to the para-aortic nodes, this local therapy technique may be considered.

Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis (AAV) Restricted to the Limbs.

A previously healthy 58-year-old man was admitted for muscle pain and weakness [manual muscle testing (MMT) of 4/4 for upper and lower limbs]. We detected elevated levels of inflammatory makers and PR3-anti-neutrophil cytoplasmic antibody (ANCA). Subsequently, the muscle weakness rapidly progressed to an MMT of 2 for all limbs. Magnetic resonance imaging indicated muscle edema, and the creatine kinase (CK) level increased to 29,998 U/L. Methylprednisolone (mPSL) and cyclophosphamide pulse therapy improved the patient symptoms. MMT recovered to 4 for all limbs. A muscle biopsy showed degenerated muscle fibers surrounded by neutrophil-predominant infiltration. In addition, lamina elastic breakdown and fibrinoid necrosis of arterioles were observed. A final diagnosis of microscopic polyangiitis (MPA) limited to the muscles was made.

Pre-Dialysis Neutrophil-Lymphocyte Ratio, a Novel and Strong Short-Term Predictor of All-Cause Mortality in Patients With Diabetic Nephropathy: Results From a Single-Center Study.

Neutrophil-lymphocyte ratio (NLR) is an inflammatory marker affecting the prognosis of end-stage renal disease (ESRD) patients. This study aimed to evaluate NLR levels predicting all-cause mortality in ESRD patients with diabetic nephropathy (DN), which have not been evaluated. We recruited 151 isolated DN patients who started hemodialysis between January 2009 and December 2014 at the Japanese Red Cross Ishinomaki Hospital. The primary outcomes were 1- and 3-year survival rates. The association between NLR and survival rate was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. Patients with an NLR ≥ 3.5 had a significantly higher mortality rate than did those with an NLR < 3.5 (log rank P = 0.02). The area under the curve (AUC) of 1-year survival for NLR was significantly larger than that for other commonly used nutritional and inflammatory variables. NLR was a more accurate predictor than other well-known markers.

Quantification of bleeding volume using computed tomography and clinical complications after percutaneous renal biopsy.

Background: The aim of this study was to investigate specific bleeding volume after percutaneous renal biopsy (PRB) and the correlation between bleeding volume and clinical parameters. Methods: A retrospective study of 252 consecutive patients (153 male patients and 99 female patients) who underwent PRB at the Department of Nephrology, Japanese Red Cross Ishinomaki Hospital, between July 2013 and January 2016 was conducted. PRB was performed under ultrasound guidance using an automated spring-loaded biopsy device and a 16-cm, 16-gauge needle. Patients underwent computed tomography (CT) the day after PRB. Bleeding volume after PRB was evaluated using reconstructed CT data. Results: The median bleeding volume after PRB was 38 mL (25th-75th percentile, 18-85 mL), with ≥4 punctures identified as a risk factor for massive bleeding. The incidence rates of macrohematuria, transient hypotension and bladder obstruction were 14.3, 8.7 and 4.7%, respectively. Post-PRB blood transfusion and intervention were required in 4.7 and 0.8% of patients, respectively. Conclusion: Although it is difficult to assess the risk for massive bleeding prior to PRB, we do provide evidence of a specific increased risk with ≥4 puncture attempts, and recommend careful follow-up of these patients.

Perirenal fat stranding is not a powerful diagnostic tool for acute pyelonephritis.

PURPOSE: Pyelonephritis, an upper urinary tract infection, is a serious infection that often requires hospitalization. However, the accurate diagnosis of acute pyelonephritis can be difficult, especially among older individuals who can present with unusual symptoms. Imaging with computed tomography (CT) is not unusual in the diagnosis of pyelonephritis, with some clinicians regarding perirenal fat stranding (PFS) as a characteristic finding. However, the sensitivity and specificity of PFS in diagnosing pyelonephritis are currently unknown. We therefore sought to clarify the relevance of PFS in diagnosing acute pyelonephritis. PATIENTS AND METHODS: We conducted a case-controlled retrospective analysis of medical records. The pyelonephritis group included 89 patients who had been diagnosed with acute pyelonephritis, while the control group included 319 patients who had undergone percutaneous renal biopsy. CT findings were available for both groups. The frequency of PFS and its sensitivity and specificity for the diagnosis of acute pyelonephritis were investigated. RESULTS: The mean ages of the pyelonephritis and control groups were 74±15 years and 63±16 years, respectively. A total of 28% of men were in the pyelonephritis group vs 61% of men in the control group. The frequency of PFS was 72% in the pyelonephritis group vs 39% in the control group. Age and renal dysfunction were associated with an increased frequency of PFS. After adjusting for age, sex, and renal function using a propensity score analysis, the sensitivity, specificity, and positive likelihood ratio of PFS for diagnosing acute pyelonephritis were 72%, 58%, and 1.7, respectively. CONCLUSION: The presence of PFS was not useful in diagnosing acute pyelonephritis.

IgG4-Related Disease Manifesting as Interstitial Nephritis Accompanied by Hypophysitis.

BACKGROUND IgG4-related disease is a systemic disease with marked infiltration of IgG4-positive plasma cells into affected organs and elevated serum IgG4. On clinical examination, swelling, nodules, and hypertrophic lesions might appear simultaneously or metachronously in different organs. CASE REPORT An 85-year-old man with sudden-onset polydipsia and polyuria insipidus was transported to our hospital because of hypothermia and general malaise. Laboratory tests revealed renal failure and central diabetes insipidus. According to his serum IgG4 level, the patient was diagnosed with possible IgG4-related kidney disease accompanied by IgG4-related hypophysitis. Abdominal contrast-enhanced computed tomography, hypophysis magnetic resonance imaging, and histological examination of the kidney were performed. Glucocorticoid therapy was administered and his renal function improved gradually. However, his central diabetes insipidus did not improve. CONCLUSIONS Glucocorticoid therapy showed different therapeutic effects on the kidney and posterior lobe of the hypophysis. It is possible that glucocorticoid therapy needs to be supported by other immunomodulatory therapies to have an effect on all affected organs.

Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m2/week for 4 weeks (i.e., the conventional lymphoma dosing schedule) is used, but the optimal dosing schedule is controversial. Indeed, a single-dose of RTX successfully controlled nephrotic syndrome. However, to date, the effectiveness of a single RTX dose in treating MPA has not been fully investigated in Japan. This was a retrospective observational study. Six newly diagnosed patients with MPA were initially treated with methylprednisolone and a single dose of RTX (375 mg/m2). We investigated the patients' clinical features, as well as the efficacy and safety of RTX treatment. All patients attained remission on a tapered prednisolone dose of < 10 mg/day during the first 12 months. One patient relapsed after 12 months whereas another required hospitalization owing to infective spondyloarthritis. Adverse reactions to RTX infusion and late-onset neutropenia were not observed. Therefore, a single-dose treatment with RTX induced remission with few complications, and allowed tapering the prednisolone treatment. We conclude that a single dose of RTX is a promising induction therapy for MPA, reducing the cost associated with multiple doses.

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors.

BACKGROUND: Reactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and ß-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays. METHODS: Ten healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg ß-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points. RESULTS: The levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus ß-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC. CONCLUSION: Tomato juice consumption may suppress human lymphocyte DNA damage caused by radiation, but further examination is required. TRIAL REGISTRATION: 2014-001 and 2014-R06.

The influence of the Great East Japan earthquake on microscopic polyangiitis: A retrospective observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis is triggered by environmental factors, including silica dust exposure. Repeated tsunami waves brought a large volume of silica-containing sludge inland after the Great East Japan earthquake in 2011. We aimed to determine if the serious disaster influenced the clinical features of the microscopic polyangiitis. METHODS: This is an observational retrospective study conducted in a single institute. A total of 43 patients were included based on the CHCC2012 criteria for microscopic polyangiitis from 2007 to 2015. We used the Poisson regression model to determine the incidence of microscopic polyangiitis within the annual population of the medical district. The participants were selected during a 3-year period from before (N = 13) to after the disaster (N = 20). The differences of parameters and the overall survival between the groups were analyzed. RESULTS: The incidence of microscopic polyangiitis increased after the disaster (λ = 17.4/million/year [95%CI: 7.66-39.6] before the disaster and λ = 33.1/million/year [17.7-61.7] after the disaster, P = 0.044). A high Birmingham Activity Score was associated with a high incidence of microscopic polyangiitis after the disaster. The overall survival of the patients with microscopic polyangiitis declined significantly after the disaster. CONCLUSIONS: The Great East Japan earthquake influenced the development of the microscopic polyangiitis in our restricted area. The patients who developed after the disaster had severe symptoms and a high mortality rate.

Renal infarct volume and renal function decline in acute and chronic phases.

BACKGROUND: Acute renal infarction (ARI) is a rare disease. ARI causes decline in renal function in both the acute and chronic phases. However, the correlation between the volume of the infarction and degree of renal function decline has not been fully investigated. Therefore, we aimed to examine the relationship between the volume of the infarction and degree of renal function decline. METHODS: We performed a single-center, retrospective, observational study investigating clinical parameters and the volume of the infarction. The volume of the infarction was measured using reconstructed computed tomography data. RESULTS: A total of 39 patients (mean age, 72.6 ± 13.2 years; men, 59%) were enrolled. The median infarction volume was 45 mL (interquartile range, 14-91 mL). The volume of the infarction was significantly associated with the peak lactate dehydrogenase (LDH) level (median, 728 IU/L; interquartile range, 491-1227 U/L) (r = 0.58, p < 0.01) and the degree of renal function decline in both acute and chronic phases (r = -0.44, -0.38, respectively, p < 0.05). The peak LDH level was significantly correlated with the degree of renal function decline in the acute phase but not in the chronic phase (r = -0.35, -0.21; p < 0.05, N.S., respectively). CONCLUSIONS: The volume of the infarction may be a factor in the degree of renal function decline in ARI. Therefore, assessment of infarct volume in ARI is important.