Development and Application of Attenuated Plant Viruses as Biological Control Agents in Japan.

In 1929, it was reported that yellowing symptoms caused by a tobacco mosaic virus (TMV) yellow mosaic isolate were suppressed in tobacco plants that were systemically infected with a TMV light green isolate. Similar to vaccination, the phenomenon of cross-protection involves a whole plant being infected with an attenuated virus and involves the same or a closely related virus species. Therefore, attenuated viruses function as biological control agents. In Japan, many studies have been performed on cross-protection. For example, the tomato mosaic virus (ToMV)-L11A strain is an attenuated isolate developed by researchers and shows high control efficiency against wild-type ToMV in commercial tomato crops. Recently, an attenuated isolate of zucchini yellow mosaic virus (ZYMV)-2002 was developed and registered as a biological pesticide to control cucumber mosaic disease. In addition, attenuated isolates of pepper mild mottle virus (PMMoV), cucumber mosaic virus (CMV), tobacco mild green mosaic virus (TMGMV), melon yellow spot virus (MYSV), and watermelon mosaic virus (WMV) have been developed in Japan. These attenuated viruses, sometimes called plant vaccines, can be used not only as single vaccines but also as multiple vaccines. In this review, we provide an overview of studies on attenuated plant viruses developed in Japan. We also discuss the application of the attenuated strains, including the production of vaccinated seedlings.

A case of renal vein thrombosis associated with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

Only a few cases of renal vein thrombosis (RVT) occurring in patients with vasculitis have been reported. RVT associated with vasculitis and hemolytic anemia has not been reported yet. We describe here a patient with RVT complicated by pulmonary embolism, autoimmune hemolytic anemia, and eosinophilic granulomatous polyangiitis. A 69-year-old Japanese man who had been treated with corticosteroids was referred to our department for severe proteinuria (4.32 g/gCr). Abdominal ultrasonography showed bilateral RVT, and contrast-enhanced computed tomography showed bilateral pulmonary embolism. Therefore, the patient was diagnosed with RVT complicated by pulmonary embolism. Anticoagulation therapy with heparin followed by apixaban was started. Thereafter, the D-dimer concentration decreased from 8.3 to 1.2 µg/mL, and urinary protein excretion improved to 0.62 g/gCr. Renal function was unchanged with an estimated glomerular filtration rate of 68.8 mL/minute/1.73 m2. The thrombi in both renal veins and pulmonary arteries gradually regressed. Clinicians should be aware of this complication when worsening proteinuria is observed during steroid therapy in patients with autoimmune hemolytic anemia and eosinophilic granulomatous polyangiitis.

Study on method of organ section retention and tracking through deep learning in automated diagnostic and therapeutic robotics.

PURPOSE: In high-intensity focused ultrasound (HIFU) treatment of the kidney and liver, tracking the organs is essential because respiratory motions make continuous cauterization of the affected area difficult and may cause damage to other parts of the body. In this study, we propose a tracking system for rotational scanning, and propose and evaluate a method for estimating the angles of organs in ultrasound images. METHODS: We proposed AEMA, AEMAD, and AEMAD++ as methods for estimating the angles of organs in ultrasound images, using RUDS and a phantom to acquire 90-degree images of a kidney from the long-axis image to the short-axis image as a data set. Six datasets were used, with five for preliminary preparation and one for testing, while the initial position was shifted by 2 mm in the contralateral axis direction. The test data set was evaluated by estimating the angle using each method. RESULTS: The accuracy and processing speed of angle estimation for AEMA, AEMAD, and AEMAD++ were 23.8% and 0.33 FPS for AEMAD, 32.0% and 0.56 FPS for AEMAD, and 29.5% and 3.20 FPS for AEMAD++, with tolerance of ± 2.5 degrees. AEMAD++ offered the best speed and accuracy. CONCLUSION: In the phantom experiment, AEMAD++ showed the effectiveness of tracking the long-axis image of the kidney in rotational scanning. In the future, we will add either the area of surrounding organs or the internal structure of the kidney as a new feature to validate the results.

A VS ultrasound diagnostic system with kidney image evaluation functions.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 resistance generated by quadruple knockout of homologs of TOBAMOVIRUS MULTIPLICATION1 in tomato.

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.

Risk Factors and Utility of Intraoperative Arteriovenous Fistula Blood Flow Level as a Surrogate Marker of Arteriovenous Fistula Failure in Patients with End-stage Renal Disease.

An arteriovenous fistula (AVF) can fail for different reasons at each stage after its creation. The study aimed to analyze the associations of the clinical and laboratory parameters, including the intraoperative AVF blood flow, with AVF failure at different periods (3 weeks and 3, 6, 9, 12, 24, and 36 months) after the AVF's creation and to evaluate the usefulness of the intraoperative AVF blood flow as a surrogate marker of AVF failure in patients with end-stage renal disease (ESRD). This was a single-center, retrospective cohort study that included 130 patients with ESRD who underwent the creation of new radiocephalic AVFs. The associations of the preoperative clinical and laboratory parameters and intraoperative flow with AVF failure in the different observation periods were investigated. Intraoperative AVF blood flow was significantly associated with AVF failure from 3 weeks to 24 months (P <0.05). Hemoglobin level and the size of the anastomosis were significantly associated with AVF failure at 6 months (P <0.05). In the analysis of the receiver operating characteristic curve, intraoperative AVF blood flow was significant from 3 weeks to 24 months (P <0.05). The intraoperative blood flow with the greatest sensitivity and specificity was 205-225 mL/min. Intraoperative blood flow was independently associated with AVF failure from 3 weeks to 24 months after the AVF's creation. An intraoperative AVF blood flow of >225 mL/min is crucial for long-term AVF patency. The intraoperative AVF blood flow level could be a surrogate marker of AVF failure in ESRD patients.

A novel complementation method of an acoustic shadow region utilizing a convolutional neural network for ultrasound-guided therapy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The effectiveness of the proposed method was demonstrated in phantom experiments. Verification of its effectiveness in real organs is necessary in future study.

No Significant Changes of Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Kidney Disease by Switching from Linagliptin to Teneligliptin.

PURPOSE: 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.

Effects of Roxadustat on the Anemia and Iron Metabolism of Patients Undergoing Peritoneal Dialysis.

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.

Relationship Between Serum Total Carbon Dioxide Concentration and Bicarbonate Concentration in Patients Undergoing Peritoneal Dialysis.

Background Few studies have assessed the relationship between serum total carbon dioxide (CO2) and bicarbonate ion (HCO3 -) concentration in patients undergoing peritoneal dialysis. We determined the agreement between serum total CO2 and HCO3 - concentration 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 patients on peritoneal dialysis. Methods We collected 245 samples of venous blood from 51 patients on peritoneal dialysis. Independent factors that correlated with the HCO3 - concentration were analyzed using multiple linear regression analysis. The diagnostic accuracy of serum total CO2 was evaluated by receiver operating characteristic (ROC) curve analysis and a 2×2 table. Agreement between serum total CO2 and HCO3 - concentration was assessed by Bland-Altman analysis. Results Serum total CO2 was independently correlated with HCO3 - concentration (ß = 0.354, p < 0.001). The area under the curve of serum total CO2 for the identification of low and high bicarbonate concentrations was 0.909. The diagnostic accuracy of serum total CO2 for the prediction of low and high bicarbonate concentrations was: sensitivity, 91.5%; specificity, 74.7%; positive predictive value, 53.5%; negative predictive value, 96.5%; and accuracy, 78.8%. Bland-Altman analysis showed a moderate agreement between serum total CO2 and HCO3 - concentration. Conclusion Serum total CO2 correlated closely with the HCO3 - concentration in patients undergoing peritoneal dialysis. Serum total CO2 might be useful for predicting low and high bicarbonate in peritoneal dialysis patients.

Idiopathic hypereosinophilic syndrome in hemodialysis patients: Case reports.

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.

Effects of Elobixibat on Constipation and Lipid Metabolism in Patients With Moderate to End-Stage Chronic Kidney Disease.

OBJECTIVE: The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD). METHODS: Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis. RESULTS: Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p < 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043). CONCLUSIONS: Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.

Factors Associated with the Change in Carotid Maximum Intima-Media Thickness in Patients with Moderate-to-Advanced Stage Chronic Kidney Disease.

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 (ß = 0.173, p < 0.05) and annual change in triglyceride (ß = 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.

Serum Zinc Concentration Correlates With Ferritin Concentration in Patients Undergoing Peritoneal Dialysis: A Cross-Sectional 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 <60 µg/dL was defined as serum zinc deficiency, and a serum zinc concentration between 60 and 80 µg/dL as possible serum zinc deficiency. Results: Serum zinc deficiency was present in 51% (25/49) of the patients, and possible serum zinc deficiency was present in 45% (22/49) of patients undergoing PD. Multivariate analysis showed that serum zinc concentration significantly correlated with serum ferritin concentration (ß = 0.357, P < 0.01). Conclusions: The prevalences of serum zinc deficiency and possible serum deficiency are high and serum zinc concentration correlates with serum ferritin concentration in patients undergoing PD.

Relationship between serum total carbon dioxide concentration and bicarbonate concentration in patients undergoing hemodialysis.

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 (ß = 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.

Cerebral oxygenation improvement is associated with hemoglobin increase after hemodialysis initiation.

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 < 0.05). Changes in cerebral rSO2 represented a significant correlation with changes in hemoglobin level, pulse rate, and serum albumin level. Multivariate linear regression analysis was performed using significant factors in simple linear regression analysis. Changes in hemoglobin (standardized coefficient: 0.37) and serum albumin (standardized coefficient: 0.45) levels were identified as independent factors influencing the changes in cerebral rSO2. 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.

Induction of hemodialysis with an arteriovenous fistula in a patient with hemophilia A.

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.

Factors Associated with Uremic Pruritus in Patients Undergoing Peritoneal Dialysis.

AIM: The aim of this study was to investigate different intensities of uremic pruritus in the daytime and nighttime, as well as contributing factors, in patients undergoing peritoneal dialysis (PD). METHODS: A total of 46 patients (31 males, 15 females) with a mean age of 59.4±14.7 years and mean PD vintage of 29.2±25.2 months were enrolled in this single-center, prospective, cross-sectional study. The intensity of uremic pruritus in the daytime and nighttime was assessed using a visual analog scale (VAS). The relationships between intensity and various clinical and laboratory parameters were analyzed using multiple linear regression analyses. RESULTS: The most common site of uremic pruritus was on the back (70%), followed by lower limbs (67%), chest and abdomen (59%), upper limbs (28%), and head and neck (22%). Mean VAS scores were higher in the nighttime compared with the daytime (4.5±3.3 vs. 3.5±2.7, P=0.02). Only male sex was correlated with higher uremic pruritus intensity in the daytime (standard coefficient [ß]=0.310, P=0.036). PD vintage (ß=0.415, P=0.004) and topical medicines, including moisturizer and topical corticosteroid use (ß=0.345, P=0.019), were independently correlated with higher uremic pruritus intensity in the nighttime. CONCLUSION: Uremic pruritus intensity was greater in the nighttime than in the daytime in PD patients. Male sex was associated with higher uremic pruritus intensity in the daytime, whereas PD vintage and topical medicine use were associated with higher uremic pruritus intensity in the nighttime.

Successful treatment of cholesterol crystal embolism with anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody: a case report.

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.

Association between carnitine deficiency and the erythropoietin resistance index in patients undergoing peritoneal dialysis: a cross-sectional observational study.

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 (ß = 0.283, p = 0.04). These results suggest that carnitine plays pivotal roles in hematogenesis in patients undergoing PD.