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An inevitable feature of ultrasound-based diagnoses is that the quality of the ultrasound images produced depends directly on the skill of the physician operating the probe. This is because physicians have to constantly adjust the probe position to obtain a cross section of the target organ, which is constantly shifting due to patient respiratory motions. Therefore, we developed an ultrasound diagnostic robot that works in cooperation with a visual servo system based on deep learning that will help alleviate the burdens imposed on physicians.Our newly developed robotic ultrasound diagnostic system consists of three robots: an organ tracking robot (OTR), a robotic bed, and a robotic supporting arm. Additionally, we used different image processing methods (YOLOv5s and BiSeNet V2) to detect the target kidney location, as well as to evaluate the appropriateness of the obtained ultrasound images (ResNet 50). Ultimately, the image processing results are transmitted to the OTR for use as motion commands.In our experiments, the highest effective tracking rate (0.749) was obtained by YOLOv5s with Kalman filtering, while the effective tracking rate was improved by about 37% in comparison with cases without such filtering. Additionally, the appropriateness probability of the ultrasound images obtained during the tracking process was also the highest and most stable. The second highest tracking efficiency value (0.694) was obtained by BiSeNet V2 with Kalman filtering and was a 75% improvement over the case without such filtering.While the most efficient tracking achieved is based on the combination of YOLOv5s and Kalman filtering, the combination of BiSeNet V2 and Kalman filtering was capable of detecting the kidney center of gravity closer to the kidney's actual motion state. Furthermore, this model could also measure the cross-sectional area, maximum diameter, and other detailed information of the target kidney, which meant it is more practical for use in actual diagnoses.

Tomato brown rugose fruit virus (ToBRFV) is an emerging virus of the genus Tobamovirus. ToBRFV overcomes the tobamovirus resistance gene Tm-22 and is rapidly spreading worldwide. Genetic resources for ToBRFV resistance are urgently needed. Here, we show that clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated targeted mutagenesis of four tomato (Solanum lycopersicum) homologs of TOBAMOVIRUS MULTIPLICATION1 (TOM1), an Arabidopsis (Arabidopsis thaliana) gene essential for tobamovirus multiplication, confers resistance to ToBRFV in tomato plants. Quadruple-mutant plants did not show detectable ToBRFV coat protein (CP) accumulation or obvious defects in growth or fruit production. When any three of the four TOM1 homologs were disrupted, ToBRFV CP accumulation was detectable but greatly reduced. In the triple mutant, in which ToBRFV CP accumulation was most strongly suppressed, mutant viruses capable of more efficient multiplication in the mutant plants emerged. However, these mutant viruses did not infect the quadruple-mutant plants, suggesting that the resistance of the quadruple-mutant plants is highly durable. The quadruple-mutant plants also showed resistance to three other tobamovirus species. Therefore, tomato plants with strong resistance to tobamoviruses, including ToBRFV, can be generated by CRISPR/Cas9-mediated multiplexed genome editing. The genome-edited plants could facilitate ToBRFV-resistant tomato breeding.

Background: Few studies have investigated the relationship between serum total carbon dioxide (CO2) concentration and bicarbonate ion (HCO3 -) concentration in patients undergoing hemodialysis. We determined the agreement and discrepancy between serum total CO2 and HCO3 - concentrations and the diagnostic accuracy of serum total CO2 for the prediction of low (HCO3 - < 24 mEq/L) and high (HCO3 - ≥ 24 mEq/L) bicarbonate concentrations in hemodialysis patients. Methods: One hundred forty-nine arteriovenous blood samples from 84 hemodialysis patients were studied. Multiple linear regression analysis was used to determine factors correlated with HCO3 - concentration. Diagnostic accuracy of serum total CO2 was evaluated using receiver operating characteristic curve analysis and a 2 × 2 table. Agreement between serum total CO2 and HCO3 - concentrations was assessed using Bland-Altman analysis. Results: Serum total CO2 concentration was closely correlated with HCO3 - concentration (β = 0.858, P < 0.001). Area under the curve of serum total CO2 for the identification of low and high bicarbonate concentrations was 0.989. Use of serum total CO2 to predict low and high bicarbonate concentrations had a sensitivity of 100%, specificity of 50.0%, positive predictive value of 96.5%, negative predictive value of 100%, and accuracy of 96.6%. Bland-Altman analysis showed moderate agreement between serum total CO2 and HCO3 - concentrations. Discrepancies between HCO3 - and serum total CO2 concentrations (serum total CO2 - HCO3 - ≤ -1) were observed in 89 samples. Conclusion: Serum total CO2 concentration is closely correlated with HCO3 - concentration in hemodialysis patients. However, there is a non-negligible discrepancy between serum total CO2 and HCO3 - concentrations.

Purpose The objective of this study was to determine factors associated with the change in carotid maximum intima-media thickness (IMT), an established surrogate marker of atherosclerosis, in moderate-to-advanced stage chronic kidney disease (CKD) patients. Methods In total, 130 moderate-to-advanced stage CKD patients (mean age: 67.6 ± 11.0 years old; 91 men and 39 women) were included in this retrospective, single-center, observational study. Relationships between the change in carotid maximum IMT and clinical and laboratory data were analyzed by using multivariate linear regression analyses. Results Mean observation period was 2.9 ± 1.6 years. Mean carotid maximum IMT at baseline was 2.2 ± 1.0 mm, and the annual change in carotid maximum IMT was 0.06 ± 0.22 mm/year. Low-density lipoprotein (LDL)-cholesterol (β = 0.173, p < 0.05) and annual change in triglyceride (β = 0.175, p < 0.05) independently correlated with the annual change in carotid maximum IMT. Conclusion Increases in LDL-cholesterol and triglyceride were associated with the rate of progression of carotid maximum IMT in moderate-to-advanced stage CKD patients.

Introduction: Near-infrared spectroscopy has been used to measure the regional oxygen saturation (rSO2) of the brain, and decreases in cerebral rSO2 have been reported to lead to cognitive impairment in patients undergoing hemodialysis. However, reports about the association between changes in cerebral oxygenation and clinical parameters at hemodialysis initiation, including hemoglobin level, are lacking. Methods: This study included 33 patients at the hemodialysis initiation phase. Cerebral rSO2 was monitored using an INVOS 5100C. Included patients were assessed twice (at hemodialysis initiation and 42.7 ± 20.8 days after the first measurement), and changes in cerebral rSO2 were compared with changes in clinical parameters. Results: Cerebral rSO2 at the second measurement significantly increased compared with that at hemodialysis initiation (57.2 ± 6.8% vs 54.4 ± 8.8%, p Conclusion: Cerebral rSO2 was low in the presence of low hemoglobin levels at hemodialysis initiation and improved in response to hemoglobin increase in addition to changes in serum albumin levels. Attention should be paid to changes in hemoglobin levels even at hemodialysis initiation to prevent the deterioration of cerebral oxygenation, and this might contribute to the maintenance of cognitive function in patients undergoing hemodialysis.

Background: We report a unique case of renal cholesterol crystal embolism (CCE) induced by carotid artery stenting that was successfully treated with evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9). Case presentation: A 77-year-old man with hypertension, hyperlipidemia, and chronic kidney disease was referred to our department for decreased estimated glomerular filtration rate (eGFR)—from 32.0 to 13.9 mL/min/1.73 m2—5 weeks after carotid artery stenting. Further examination revealed livedo reticularis in the bilateral toes and eosinophilia (723/μL). Skin biopsy from livedo reticularis tissue in the bilateral toes showed cholesterol clefts in the small arteries. The patient was therefore diagnosed with CCE. After 25 weeks’ administration of evolocumab at a dose of 140 mg subcutaneously administered every 2 weeks, his eGFR had improved from 10.7 to 18.1 mL/min/1.73 m2. Conclusion: Evolocumab may have a beneficial effect on renal involvement in patients with CCE.

Carnitine deficiency contributes to developing various pathological conditions, such as cardiac dysfunction, muscle weakness, and erythropoietin-resistant anemia in patients undergoing hemodialysis. However, a conclusion has not been reached concerning the prevalence and the effect of carnitine deficiency in patients undergoing peritoneal dialysis (PD). In this study, the prevalence of carnitine deficiency and the clinical factors associated with carnitine deficiency were investigated in 60 patients undergoing PD. The median age of the patients was 62.5 years (52.5–72.5 years), the proportion of male sex was 44/60 (73.3%), and the median PD period was 24 months (12–45 months). Carnitine deficiency (acyl carnitine/free carnitine ratio >0.4) was detected in 56/60 (93%) patients. Multiple regression analysis showed that the erythropoietin resistance index was independently associated with carnitine deficiency (β = 0.283, p = 0.04). These results suggest that carnitine plays pivotal roles in hematogenesis in patients undergoing PD.

Keiji Hirai, Junki Morino, Saori Minato, Shohei Kaneko, Katsunori Yanai, Yuko Mutsuyoshi, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Mitsutoshi Shindo, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-Cho, Omiya-Ku, Saitama City, Saitama 330-8503, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpIntroduction and Objectives: We investigated the efficacy and safety of sodium-glucose cotransporter-2 (SGLT-2) inhibitors as an add-on therapy in patients with advanced-stage diabetic kidney disease taking renin-angiotensin system (RAS) blockers.Materials and Methods: Changes in glycated hemoglobin (HbA1c), urine protein-to-creatinine ratio (UACR), body weight, systolic blood pressure, and annual change in estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 20 patients after 12 months of SGLT-2 inhibitor administration (mean eGFR: 22.8 ± 9.7 mL/min/1.73 m2). All patients had advanced-stage diabetic kidney disease and were taking RAS blockers. Twenty patients matched with similar propensity scores who were not taking SGLT-2 inhibitors served as the control group.Results: The annual change in eGFR improved significantly from − 8.6 ± 12.5 mL/min/1.73 m2/year to − 2.6 ± 5.0 mL/min/1.73 m2/year after 12 months by SGLT-2 inhibitor administration (p < 0.05), but did not change in the control group. Other clinical parameters, such as HbA1c, UACR, body weight, blood pressure, serum lipids, and electrolytes did not change in either group. No adverse effects were observed by taking SGLT-2 inhibitors.Conclusion: Using SGLT-2 inhibitors as an add-on therapy may have beneficial effects on renal function in patients with advanced-stage diabetic kidney disease taking RAS blockers without any adverse effects.Keywords: advanced-stage diabetic kidney disease, renin-angiotensin system blocker, sodium-glucose cotransporter-2 inhibitor

Keiji Hirai, Hiroaki Nonaka, Moeka Ueda, Junki Morino, Shohei Kaneko, Saori Minato, Yuko Mutsuyoshi, Katsunori Yanai, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpPurpose: We compared the efficacy of teneligliptin versus linagliptin for glycemic control and renoprotection in patients with advanced-stage diabetic kidney disease.Patients and Methods: Changes in the glycated hemoglobin (HbA1c), fasting blood glucose concentration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) during a 12-month period were retrospectively analyzed after switching from linagliptin to teneligliptin in 13 patients with advanced-stage diabetic kidney disease (teneligliptin group). Thirteen propensity score-matched patients who were treated with linagliptin alone served as controls (linagliptin group).Results: The HbA1c, fasting blood glucose concentration, and UACR did not change during the 12-month study period in either group. The annual change rate in the eGFR did not differ between before and after baseline in either group.Conclusion: Switching from linagliptin to teneligliptin may not improve glycemic control, reduce urinary protein excretion, or ameliorate the rate of renal function decline in patients with advanced-stage diabetic kidney disease. These results suggest that teneligliptin may not be more advantageous for glycemic control and renoprotection compared with linagliptin in patients with advanced-stage diabetic kidney disease.Keywords: chronic kidney disease, diabetic kidney disease, teneligliptin, linagliptin

Background: We investigated the effects of roxadustat on the anemia, iron metabolism, peritoneal membrane function, and residual renal function; and determined the factors associated with the administration of roxadustat in patients who were undergoing peritoneal dialysis.Methods: We retrospectively analyzed the changes in hemoglobin, serum ferritin, transferrin saturation (TSAT), 4-h dialysate/plasma creatinine, and renal weekly urea clearance over the 24 weeks following the change from an erythropoiesis-stimulating agent (ESA) to roxadustat in 16 patients who were undergoing peritoneal dialysis and had anemia (Roxadustat group). Twenty-three peritoneal dialysis patients who had anemia and continued ESA served as a control group (ESA group).Results: There were no significant differences in hemoglobin, serum ferritin, TSAT, 4-h dialysate/plasma creatinine, or renal weekly urea clearance between the two groups at baseline. The hemoglobin concentration was significantly higher in the Roxadustat group than in the ESA group after 24 weeks (11.6 ± 1.0 g/dL vs. 10.3 ± 1.1 g/dL, p < 0.05), whereas the ferritin concentration and TSAT were significantly lower (139.5 ± 102.0 ng/mL vs. 209.2 ± 113.1 ng/mL, p < 0.05; and 28.1 ± 11.5% vs. 44.8 ± 10.4%, p < 0.05, respectively). The changes in 4-h dialysate/plasma creatinine and renal weekly urea clearance did not differ between the two groups. Linear regression analysis revealed that the serum potassium concentration correlated with the dose of roxadustat at 24 weeks (standard coefficient = 0.580, p = 0.019).Conclusion: Roxadustat may improve the anemia and reduce the serum ferritin and TSAT of the peritoneal dialysis patients after they were switched from an ESA, without association with peritoneal membrane function or residual renal function.

Background:Although cerebral regional oxygen saturation (rSO2) is significantly lower in hemodialysis (HD) patients than that in healthy controls, investigations on cerebral oxygenation in peritoneal dialysis (PD) patients are limited. We aimed to confirm the cerebral oxygenation status and identify the factors affecting cerebral rSO2in PD patients.Methods:Thirty-six PD patients (21 men and 15 women; mean age, 62.8 ± 12.7 years) were recruited. In addition, 27 healthy volunteers (17 men and 10 women; mean age, 43.5 ± 18.8 years) were recruited as a control group. Cerebral rSO2was monitored at the forehead using an INVOS 5100c oxygen saturation monitor.Results:Cerebral rSO2was significantly lower in PD patients than that in healthy controls (57.0 ± 7.3% vs 68.9 ± 8.6%, p 2was significantly correlated with natural logarithm (Ln)-PD duration ( r = −0.389, p = 0.019) and serum albumin concentration ( r = 0.370, p = 0.026) in a simple linear regression analysis. Multivariable linear regression analysis was performed using variables that showed a significant correlation and p 2. Cerebral rSO2was independently associated with Ln-PD duration (standardized coefficient: −0.339) and serum albumin concentration (standardized coefficient: 0.316).Conclusions:Cerebral rSO2was significantly affected by the PD duration and serum albumin concentration. Further prospective studies are needed to clarify whether preventing a decrease in serum albumin concentration leads to the maintenance of cerebral oxygenation in patients undergoing PD.

Hemodialysis (HD) patients frequently experience severe anemia, requiring intradialytic blood transfusion. Severe anemia leads to deterioration of systemic tissue oxygenation. However, few reports have examined the effect of intradialytic blood transfusion on tissue oxygenation changes. This study aimed to (i) monitor the differences in tissue oxygenation in the brain and liver during intradialytic blood transfusion, and (ii) elucidate the clinical factors affecting cerebral and hepatic oxygenation. Thirty-eight HD patients with severe anemia requiring intradialytic blood transfusion were included (27 men, 11 women; mean age, 70.2 ± 1.6 years). Cerebral and hepatic regional oxygen saturation (rSO2) values were monitored using near-infrared spectroscopy (INVOS 5100c oxygen saturation monitor). Cerebral and hepatic rSO2 were significantly higher after than before blood transfusion (p

We herein report two cases of advanced stage rapidly progressive diabetic nephropathy that were effectively treated with combination therapy including renin–angiotensin–aldosterone system (RAS) blocker [angiotensin II receptor blocker (ARB)], glucagon-like peptide-1 (GLP-1) receptor agonist and sodium glucose transporter-2 (SGLT-2) inhibitor. A 30-year-old woman with advanced stage diabetic nephropathy [estimated glomerular filtration rate (eGFR): 20.7 mL/min/1.73 m(2); proteinuria: 13.2 g/gCr], showing a rapidly progressive pattern (annual eGFR change: − 60.0 mL/min/1.73 m(2)/year), had improvement in proteinuria (5.9 g/gCr) and eGFR change (+ 4.3 mL/min/1.73 m(2) over 15 weeks) after administration of ARB (irbesartan 25 mg/day), GLP-1 receptor agonist (liraglutide 0.3 mg/day) and SGLT-2 inhibitor (canagliflozin 50 mg/day). A 59-year-old man with advanced stage diabetic nephropathy (eGFR: 32.4 mL/min/1.73 m(2); proteinuria: 8.90 g/gCr), showing a rapidly progressive pattern (annual eGFR change: − 21.2 mL/min/1.73 m(2)/year), had an improvement in proteinuria (0.02 g/gCr) and annual eGFR change (+ 0.1 mL/min/1.73 m(2)/year) after combination therapy with ARB (olmesartan 40 mg/day), GLP-1 receptor agonist (liraglutide 0.9 mg/day) and SGLT-2 inhibitor (tofogliflozin 10 mg/day). These results suggest that this triple combination therapy has renoprotective effects on advanced stage rapidly progressive diabetic nephropathy.

While Fusarium graminearum readily produces trichothecenes in complex media containing sucrose as the carbon source (YS_60), the amount of the mycotoxin is quite limited when other sugars, such as glucose and fructose, are used. We found that autoclaving of media containing fructose and yeast extract (YF_60) results in the formation of inhibitors of trichothecene biosynthesis by F. graminearum JCM 9873, a strain that produces 15-acetyldeoxynivalenol (15-ADON) in liquid culture. Removal of the solvent fraction from the autoclaved media after ethyl acetate extraction attenuated the inhibitory activity against trichothecene production. In addition, extraction of the non-autoclaved complex media with ethyl acetate, followed by removal of the solvent fraction, similarly resulted in increased accumulation of the mycotoxin. Although the increase in trichothecene production differed considerably among fungal strains and yeast extract products, F. graminearum species complex generally responded to the medium treatments in the same way. These results suggest that some hydrophobic substances that arise during the drying and heating of yeast extract negatively affected trichothecene production in liquid culture. Modes of actions of inhibitory substances were partially characterized using strain JCM 9873, with focus on the transcriptional and functional analyses of Tri6, a key regulator gene in trichothecene biosynthesis. The presence of the ethyl acetate-extractable substances in autoclaved YF_60 media decreased the relative transcription level of Tri6, as well as that of a trichodiene synthase gene Tri5. Thus, the substances exerted their inhibitory action through suppression of Tri6 expression. By using a yeast extract lot that completely prevented trichothecene production by the wild-type strain in autoclaved YS_60 medium, we prepared YF_60 media and cultured a constitutive Tri6 overexpressor strain described by Maeda et al. (2018). Despite the high transcription level of Tri6, the presence of the ethyl acetate extractable-substances suppressed 15-ADON production. These results suggested that both Tri6p-independent initial activation of Tri6 expression and subsequent Tri6p-dependent activation of Tri expression were affected by the hydrophobic substances in the yeast extract products.

Noise-free ultrasound images are essential for organ monitoring during regional ultrasound-guided therapy. When the affected area is located under the ribs, however, acoustic shadow is caused by the reflection of sound from hard tissues such as bone, and the image is output with missing information in this region. Therefore, in the present study, we attempt to complement the image in the missing area. The overall flow of the complementation method to generate a shadow-free composite image is as follows. First, we constructed a binary classification method for the presence or absence of acoustic shadow on a phantom kidney based on a convolutional neural network. Second, we created a composite shadow-free image by searching for a suitable image from a time-series database and superimposing the corresponding area without shadow onto the missing area of the target image. In addition, we constructed and verified an automatic kidney mask generation method utilizing U-Net. The complementation accuracy for kidney tracking could be enhanced by template matching. Zero-mean normalized cross-correlation (ZNCC) values after complementation were higher than that of before complementation under four different data generation conditions: (i) changing the position of the bed of the robotic ultrasound diagnostic system in the translational direction, (ii) changing the probe angle in the translational direction, (iii) with the addition of rotational motion of the probe to condition (ii). Although there was large variation in the shape of the kidney contour in condition (iii), the proposed method improved the ZNCC value from 0.5437 to 0.5807. The effectiveness of the proposed method was demonstrated in phantom experiments. Verification of its effectiveness in real organs is necessary in future study.

Background: Zinc deficiency is common and is associated with erythropoietin resistant anemia, dysgeusia, and hypogonadism in patients undergoing hemodialysis. However, the prevalence and clinical effects of zinc deficiency in patients undergoing peritoneal dialysis (PD) have not been determined.Methods: This was a retrospective, cross-sectional study. The prevalence of serum zinc deficiency and the clinical factors related to serum zinc concentration were determined in 49 patients undergoing PD [mean age 59.5 years (±14.8 years), 38/49 were men (78.6%), median PD period 24.0 months (12.5–45.0 months)]. A serum zinc concentration

A fixed-dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti-HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance-associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region. After the treatment, eight patients successfully achieved virus eradication and sustained a virological response at 12 weeks (SVR12). In addition, mac-2 binding protein glycosylation isomer (M2BPGi), a biomarker for liver fibrosis, was reduced after the therapy. Two patients withdrew from the therapy due to the development of erythema multiforme and a strong drowsiness, respectively. These results suggest that triple therapy combining OBV, PTV and RTV is effective in achieving SVR12 in most of the HCV-infected patients on HD. In addition, this combination therapy contributed to retard the progression of liver fibrosis. However, we suggest that further trial will be required to establish its clinical efficacy and safety.

Fusarium species are traditionally grouped into type A and type B trichothecene producers based on structural differences in the mycotoxin they synthesize. The type B trichothecene-producing Fusarium graminearum strains are further divided into 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and nivalenol (NIV) chemotypes. The former two chemotypes, collectively termed a deoxynivalenol (DON) chemotype, evolved from a NIV chemotype by inactivation of FgTri13, which encodes trichothecene C-4 hydroxylase, during the evolutionary process. Despite stable overexpression of FgTri13, however, both 3-acetylnivalenol (3-ANIV) and 3-ADON accumulate equally in shake flask culture of a transgenic 3-ADON chemotype. In this study, we investigated why the "3-ANIV chemotype" could not be obtained using this strategy. When analysis was extended to the transgenic NIV chemotype, in which FgTri7 C-4 acetylase gene was disrupted and FgTri8 deacetylase gene was replaced with the 3-ADON chemotype's orthologue, C-4 unoxygenated 3-ADON, as well as C-4 oxygenated 3-ANIV, accumulated as the end product. A feeding experiment with an ΔFgtri5ΔFgtri3 double gene disruptant, a trichothecene non-producing mutant unable to acetylate C-15 of the trichothecene ring, revealed the importance of the 15-O-acetyl group for efficient C-4 hydroxylation of DON-type trichothecenes. This implies that traditional DON and NIV chemotype diversification is not solely explained by FgTri13, but is also explained by the function of the FgTri8 trichothecene deacetylase gene. None of the crude cell extracts from existing chemotypes showed highly specific C-15 deacetylation activity against 3,15-diacetylnivalenol (3,15-diANIV) without deacetylating C-15 of the C-4 unoxygenated earlier intermediate, 3,15-diacetyldeoxynivalenol. Thus, an unnatural Fusarium trichothecene, 3-ANIV, could only be synthesized as part of a mixture with 3-ADON, unless the esterase encoded by FgTri8 evolves to act on the 15-O-acetyl of 3,15-diANIV with high specificity. We also explain why the transgenic "15-ANIV chemotype", which can be generated through functional inactivation of FgTri7, uses an engineered pathway via 3,15-diANIV, but not 15-ADON, to generate 15-ANIV. Tri genes appear to evolve continuously, and altered functions of trichothecene pathway enzymes result in the generation of new trichothecenes, such as NX-2 and NX-3, which have been recently discovered in field isolates of F. graminearum. As recombination of FgTri8 between existing F. graminearum isolates could give rise to a strain that produces mixtures of DON and NIV-type trichothecenes, it may also be noteworthy to monitor the emergence of a field isolate that invalidates traditional chemotype classification.

An 88-year-old man with congenital hemophilia A developed end-stage renal disease due to microscopic polyangiitis. He was at risk for catheter-related infection because he was taking immunosuppressive agents for the treatment of polyangiitis. He was also unable to manipulate the peritoneal dialysis device. Therefore, hemodialysis using an arteriovenous fistula was induced for renal replacement therapy. Recombinant coagulation factor VIII (1000 IU) was administered via the venous chamber of the hemodialysis circuit 10 min before the end of each hemodialysis session, and nafamostat mesylate (25 mg/h) was employed as an anticoagulant during hemodialysis. His clotting factor VIII activity level increased to > 50% and activated partial thromboplastin time decreased to 50 s at the end of each hemodialysis session. This method allowed him to achieve hemostasis at the puncture site of the arteriovenous fistula and undergo stable hemodialysis with no complications, including bleeding. This case suggests that hemodialysis using an arteriovenous fistula with coagulation factor replacement and nafamostat mesylate in each hemodialysis session is a therapeutic option for end-stage renal disease in patients of advanced age with hemophilia at high risk of bleeding.

Rationale Herein, we report 3 hemodialysis patients with idiopathic hypereosinophilic syndrome who were successfully treated using corticosteroid therapy. Patient concerns Case 1 was a 63-year-old man who was undergoing hemodialysis because of bilateral nephrectomy and developed hypereosinophilia with digestive symptoms, myocardial injury, and intradialytic hypotension. Case 2 was an 83-year-old man who was undergoing hemodialysis because of nephrosclerosis and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. Case 3 was a 59-year-old man who was undergoing hemodialysis because of diabetic nephropathy and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. Diagnoses All 3 patients presented with hypereosinophilia (eosinophil count ≥1500 /μL for more than 1 month) and multiple-organ involvement (intradialytic hypotension, cardiac injury, digestive symptoms, and allergic dermatitis). A specific cause for the hypereosinophilia was not identified by systemic computed tomography, electrocardiography, echocardiography, bone marrow examination, or blood tests. Furthermore, Case 2 and 3 had not recently started taking any new drugs and drug-induced lymphocyte stimulation tests were negative in Case 1. Therefore, they were diagnosed with idiopathic hypereosinophilic syndrome. Interventions All 3 patients received corticosteroid therapy with prednisolone at a dose of 40 mg/d, 30 mg/d, and 60 mg/d in Case 1, 2, and 3, respectively. Outcomes Their digestive symptoms, pruritus, intradialytic hypotension, and serum troponin I concentrations were immediately improved alongside reductions in their eosinophil counts. Lessons There have been few case reports of idiopathic hypereosinophilic syndrome in patients undergoing hemodialysis. We believe that recording of the clinical findings and treatments of such patients is mandatory to establish the optimal management of idiopathic hypereosinophilic syndrome.

A fixed-dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti-HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance-associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region. After the treatment, eight patients successfully achieved virus eradication and sustained a virological response at 12 weeks (SVR12). In addition, mac-2 binding protein glycosylation isomer (M2BPGi), a biomarker for liver fibrosis, was reduced after the therapy. Two patients withdrew from the therapy due to the development of erythema multiforme and a strong drowsiness, respectively. These results suggest that triple therapy combining OBV, PTV and RTV is effective in achieving SVR12 in most of the HCV-infected patients on HD. In addition, this combination therapy contributed to retard the progression of liver fibrosis. However, we suggest that further trial will be required to establish its clinical efficacy and safety.

A 58-year-old man visited a local clinic after experiencing epigastric and dorsal pain. A computed tomography scan revealed a hypovascular mass in the pancreatic tail. T1-weighted magnetic resonance imaging (MRI) of the tumor showed a heterogeneous isointense signal and T2-weighted MRI showed a hyperintense signal. Contrast studies revealed contrast enhancement, showing a cystic wall and parts of a septal structure and lumen. Endoscopic ultrasonography revealed a multilocular hypoechoic tumor containing large quantity of debris. We experienced difficulty arriving at a diagnosis and are reporting this case of a pancreatic dermoid cyst, which was diagnosed based on pathological findings.