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Introduction Transplant renal vein thrombosis is a serious post‐transplant complication. We report a case in which a thrombus was found in the transplant renal vein and rescued the transplanted kidney utilizing interventional radiology. Case presentation A 56‐year‐old woman underwent ABO‐compatible living donor renal transplantation due to impaired renal function caused by IgA nephropathy. On postoperative Day 13, there was a finding on transplant renal echocardiography that appeared to be an interruption of peripheral renal blood flow in diastole. Contrast‐enhanced computed tomography revealed that the vein was occluded due to the hematoma, and thrombosis was observed within, and distal contrast showed regurgitation into the collateral vessels. The stenosis was breached and balloon dilation restored progressive blood flow through interventional radiology. Conclusion Although open surgical thrombectomy is mainly considered for treatment for transplant renal vein thrombosis, interventional radiology might be the alternative treatment option.

Abstract Background The Mt FUJI study was a multicenter, prospective, randomized, single‐blind, controlled trial comparing delivery catheter‐based and stylet‐based right ventricular (RV) lead placement at the RV septum. This study extended the follow‐up duration to 1 year after implantation. Methods Seventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid‐term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events. Results At the 1‐year follow‐up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, p = .332), BNP levels (+8.0 [−11.1, 26.5] pg/mL vs. −8.7 [−15.3, 13.2] pg/mL, p = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, p

Introduction Advanced urachal carcinoma has a poor prognosis; however, a standard systemic treatment has not been established. We treated a patient with relapsed urachal carcinoma with capecitabine‐oxaliplatin plus bevacizumab, a standard regimen for colon cancer, and obtained favorable responses. Case presentation A 47‐year‐old woman presented with hematuria. Under the diagnosis of non‐metastatic urachal carcinoma, an extended partial cystectomy was performed. Histopathological examination revealed adenocarcinoma with negative surgical margins and lymph nodes. Thirty‐two months postoperatively, lung metastases and local recurrence were confirmed, along with elevated carcinoembryonic antigen levels, and nine chemotherapy cycles were administered. Subsequently, the recurrent lesion regressed, and tumor marker levels normalized. Fourteen months after treatment discontinuation, the disease remained stable without progression. Conclusion This is the first report of advanced urachal carcinoma treated with capecitabine‐oxaliplatin plus bevacizumab, demonstrating the potential of this treatment as first‐line chemotherapy for this disease.

Introduction Prostate biopsy is commonly performed using a transrectal ultrasound probe through a transrectal or transperineal approach. However, this is not possible for patients without a rectum. Case presentation A 75‐year‐old male was referred to our hospital because of an elevated prostate‐specific antigen and a suspicious prostate lesion (PIRADS 5) in the left peripheral zone. The patient had previously undergone abdominoperineal resection for rectal cancer, which excluded the use of transrectal ultrasound. We describe the use of the transperineal ultrasound‐guided biopsy with cognitive magnetic resonance imaging‐transperineal ultrasound fusion and the utility of the injection of bubbled lidocaine jelly into urethra to improve its visualization. The pathological findings revealed clinically significant cancer with a Gleason score of 5 + 4. Conclusion Cognitive magnetic resonance imaging‐transperineal ultrasound fusion transperineal prostate biopsy with injection of bubbled jelly into urethra is a feasible and practical technique that does not require any specialized equipment.

Key Clinical Message An elderly patient with upper back pain and hypertension was diagnosed as having spontaneous spinal epidural hematoma (SSEH) after excluding artery dissection. The initial symptoms of SSEH mimic those of artery dissection, and the symptoms of spinal damage frequently appear later. Physicians should, therefore, be mindful of SSEH.

Introduction Here we present a rare case of hepatocellular carcinoma metastasis to the urinary bladder in a patient with metastatic HCC. Case presentation An 83‐year‐old man developed gross hematuria during combined treatment with an anti‐programmed death‐ligand 1 inhibitor and an anti‐vascular endothelial growth factor for metastatic HCC. A contrast‐enhanced CT revealed a 15 × 15 mm soft tissue mass protruding from the posterior bladder wall. Cystoscopy further revealed a solitary submucosal mass located on the posterior wall. The patient underwent transurethral resection of bladder tumor. The pathological findings were consistent with a diagnosis of bladder metastasis from HCC. Following a 3‐week interval after the surgical intervention, salvage therapy was resumed. Conclusion During follow‐up after TUR‐BT in HCC patients who present with a bladder tumor, the possibility of HCC metastases to the urinary bladder should be excluded.

Abstract Aim Alcohol use disorder (AUD) is frequently accompanied by comorbid attention‐deficit hyperactivity disorder (ADHD). Comorbid ADHD has been reported to increase the severity of AUD. We investigated whether ADHD severity also influences AUD relapse risk at baseline and after inpatient treatment. Methods In this study, 187 AUD patients admitted to Narimasu Kosei Hospital from October 2019 to March 2021 were included in the analysis. According to the Adult ADHD Self‐Report Scale (ASRS), participants were divided into two groups: ASRS+ with ADHD characteristics (n = 43) and ASRS− with low/no ADHD characteristics (n = 144). Groups were compared for AUD relapse risk at the start of treatment (baseline) and before hospital discharge using the multidimensional Alcohol Relapse Risk Scale (ARRS). The change in relapse risk during hospitalization was also compared by assessment of the interaction between groups (ASRS+ vs. ASRS−) and time (at discharge vs. baseline). Results The total ARRS score and dimension subscores for stimulus‐induced vulnerability and emotionality problems were significantly higher in the ASRS+ group at baseline and before discharge compared to the ASRS− group. There was a significant group × time interaction indicating less improvement of stimulus‐induced vulnerability during inpatient treatment among the ASRS+ group compared to the ASRS− group. Conclusions Our findings suggest that AUD patients with ADHD characteristics have a higher risk of relapse both at baseline and after inpatient treatment. Stimulus‐induced vulnerability to relapse is less likely to improve with treatment in patients with ADHD characteristics.

Abstract Background and Aim Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan–Meier analysis with propensity score matching and logistic progression analysis. Results The cumulative risk of developing a new symptom after 10 and 20 years of follow‐up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033–1.165; P = 0.002), the serum D‐Bil level (HR, 6.262; 95% CI, 2.522–15.553, P

Nonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline‐deficient, methionine‐lowered, l‐amino acid‐defined high‐fat diet (CDAHFD). CDAHFD with insufficient methionine induced insulin sensitivity and enhanced NASH pathology, but without obesity. In contrast, CDAHFD with sufficient methionine induced steatosis, and unlike CDAHFD with insufficient methionine, also induced obesity and insulin resistance. Gene profile analysis revealed that the disease severity in CDAHFD may partially be due to upregulation of the Rho family GTPases pathway and mitochondrial and nuclear receptor signal dysfunction. The signaling factors/pathways detected in this study may assist in future study of NASH regulation, especially its ‘nonobese’ subtype.

Abstract Introduction Conventional Doppler measurements have limitations in predicting left ventricular diastolic dysfunction (LVDD) in patients with mitral regurgitation (MR). Recently, electrocardiographic P‐wave peak time (PWPT) has been proposed as a parameter of detecting LVDD. This study aimed to evaluate the association between PWPT and left ventricular end‐diastolic pressure (LVEDP) in patients with MR. Methods We performed echocardiography and cardiac catheterization in 82 patients with moderate or severe MR. We classified patients into two groups: low LVEDP group (L‐LVEDP) (LVEDP

Abstract Materials that can efficiently convert heat into electricity are widely utilized in energy conversion technologies. The existing thermoelectrics demonstrate rather limited performance characteristics at room temperature, and hence, alternative materials and approaches are very much in demand. Here, it is experimentally shown that manipulating an applied stress can greatly improve a thermoelectric power factor of layered p‐type SnSe single crystals up to ≈180 µW K−2 cm−1 at room temperature. This giant enhancement is explained by a synergetic effect of three factors, such as: band‐gap narrowing, Lifshitz transition, and strong sample deformation. Under applied pressure above 1 GPa, the SnSe crystals become more ductile, which can be related to changes in the prevailing chemical bonding type inside the layers, from covalent toward metavalent. Thus, the SnSe single crystals transform into a highly unconventional crystalline state in which their layered crystal stacking is largely preserved, while the layers themselves are strongly deformed. This results in a dramatic narrowing in a band gap, from Eg = 0.83 to 0.50 eV (at ambient conditions). Thus, the work demonstrates a novel strategy of improving the performance parameters of chalcogenide thermoelectrics via tuning their chemical bonding type, stimulating a sample deformation and a band‐structure reconstruction.

Introduction Ureteropelvic junction obstruction associated with ureteral duplication is rare, with prevalence reported to be around 2–7%. Ureteropelvic junction obstruction of the lower pole with both complete and incomplete duplex systems is a common cause of obstruction. Here, we report a case of ureteropelvic junction obstruction associated with incomplete ureteral duplication of the solitary kidney successfully treated by pyeloureterostomy. Case presentation The patient was a 39‐year‐old woman who presented with right hydronephrosis, right back pain, and deteriorated renal function. The patient was referred to our department from the rheumatology department. Her medical history included congenital left renal hypoplasia, Sjogren's syndrome, and hyperphospholipid antibody syndrome. Conclusion We encountered a case of hydronephrosis occurring in a solitary kidney with incomplete ureteral duplication. This case was successfully managed after pyeloureterostomy.

Abstract Lemborexant, a recently approved dual orexin receptor antagonist for treatment of adults with insomnia, is eliminated primarily by cytochrome P450 (CYP)3A metabolism. The recommended dose of lemborexant is 5 mg once per night, with a maximum recommended dose of 10 mg once daily. A physiologically‐based pharmacokinetic (PBPK) model for lemborexant was developed and applied to integrate data obtained from in vivo drug–drug interaction (DDI) assessments, and to further explore lemborexant interaction with CYP3A inhibitors and inducers. The model predictions were in good agreement with observed pharmacokinetic data and with DDI results from clinical studies with CYP3A inhibitors, itraconazole and fluconazole. The model further predicted that DDI effects of weak CYP3A inhibitors (fluoxetine and ranitidine) are weak, and effects of moderate inhibitors (erythromycin and verapamil) are moderate. Based on the PBPK simulations and clinical efficacy and safety data, the maximum daily recommended lemborexant dose when administered with weak CYP3A inhibitors is 5 mg; co‐administration of moderate and strong inhibitors should be avoided except in countries where 2.5 mg has been approved.

Abstract Aims/Introduction The association between diabetes and periodontal disease is considered to be bidirectional. However, there is still controversy surrounding the relationship between periodontal disease and type 1 diabetes. We investigated whether insulin improves periodontitis without any local treatments for periodontitis under type 1 diabetes conditions using the ligature‐induced experimental periodontitis model. Materials and Methods Type 1 diabetic rats were induced by streptozotocin injection. Experimental periodontitis was induced by ligature in normal and diabetic rats. Half of the diabetic rats were treated with insulin. Two weeks after the ligature, periodontitis was evaluated. Results Insulin treatment significantly improved inflammatory cell infiltration and inflammatory cytokine gene expression, leading to suppression of alveolar bone loss, in the periodontitis of diabetic rats. Insulin also suppressed the periodontitis‐increased nitric oxide synthase‐positive cells in periodontal tissue of the diabetic rats. Even without induction of periodontitis, diabetic rats showed decreased gingival blood flow and an increased number of nitric oxide synthase‐positive cells in the gingiva and alveolar bone loss compared with normal rats, all of which were ameliorated by insulin treatment. We further confirmed that insulin directly suppressed lipopolysaccharide‐induced inflammatory cytokine expressions in THP‐1 cells. Conclusions There were abnormalities of periodontal tissue even without the induction of periodontitis in streptozotocin‐induced diabetic rats. Insulin treatment significantly ameliorated periodontitis without local periodontitis treatment in diabetic rats. These data suggest the therapeutic impacts of insulin on periodontitis in type 1 diabetes.

Introduction Renal cell carcinoma has been considered radioresistant. Recently, several studies have reported the efficacy of combination therapy using radiotherapy and immune checkpoint inhibitors. Case presentation In 1999, a 56‐year‐old woman underwent left nephrectomy (clear cell carcinoma, pT1bN0M0). Seventeen years postoperatively, recurrence in the left lung hilum was observed. Despite administration of three molecular target drugs, all treatments were terminated due to adverse events. Nivolumab was initiated in December 2016. In August 2017, subcutaneous and lung metastases were observed. Moreover in January 2018, right renal metastasis was noted. After 22 cycles of nivolumab treatment, metastasis in the iliac bone was observed, and the patient was subjected to conventional palliative external beam radiation therapy. Five months after radiotherapy, there was significant reduction in multiple metastases. Here, we reported the case presenting with possible abscopal effect. Conclusion Radiotherapy combined with immune checkpoint inhibitors may induce systemic effects against metastatic renal carcinoma.

Abstract Background Philadelphia‐negative (Ph‐negative) myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are exceptionally rare during childhood. Thus, clinical features of pediatric Ph‐negative MPNs remain largely unknown. This study was therefore performed to address this. Methods We performed a retrospective study to collect clinical information of children diagnosed with Ph‐negative MPNs from 2000 to 2016 using questionnaires in qualified institutions in Japan. The results obtained from the questionnaire survey were then combined with those from the national registry data. Results Among 50 children identified, five had PV, 44 had ET, and one had PMF. Median age at diagnosis was 14.0, 9.0, and 0 years, respectively. Male to female ratio was 4:1, 21:23, and 1:0, respectively. Detection rates of the JAK2 V617F variant were 0/5 in PV and 9/39 in ET. Frequencies of complications, such as thrombosis and subsequent leukemia, were lower than complication frequencies in adults. We identified two children who developed subsequent leukemia, which has not been reported previously, and one of them died. Conclusion This is the first nationally representative survey of pediatric Ph‐negative MPNs. Given its rarity, an international collaboration with comprehensive genetic analyses might be needed to fully elucidate the clinical and genetic features.

Abstract Aims As an extension of a phase 2/3 study evaluating the efficacy and safety of lisdexamfetamine dimesylate (LDX) 30, 50, or 70 mg/d for 4 weeks in Japanese patients aged 6‐17 years with attention‐deficit/hyperactivity disorder (ADHD), this study evaluated its long‐term safety and efficacy. Methods This was a multicenter, open‐label study of LDX for 53 weeks. Safety was assessed by regular medical examination for treatment‐emergent adverse events (TEAEs); regular recording of body weight, vital signs, and laboratory test values; and completion of dependence questionnaires. Efficacy was assessed using Japanese versions of the ADHD‐Rating Scale‐IV (ADHD‐RS‐IV) and Conners' 3rd edition Parent Rating Scale (Conners 3); plus Clinical Global Impression‐Improvement (CGI‐I), Clinical Global Impression‐Severity, and Parent Global Assessment (PGA) scales. Results Of 132 enrolled patients, 104 completed the trial. Most frequent treatment‐related TEAEs were decreased appetite (73.5%), initial insomnia (39.4%), and weight decrease (22.0%). Most TEAEs were mild (82.6% of patients). There were no serious or severe TEAEs or deaths. No treatment‐related TEAEs were associated with blood pressure or pulse rate, and no patient had a QTcF interval >500 ms. Statistically significant improvement from baseline to week 53 was observed in the mean ADHD‐Rating Scale‐IV total score and mean Conners 3 subscale scores. Most patients showed improvement on the CGI‐I (78%) and PGA (76.5%) scales. Conclusions No significant safety issues were observed with LDX 30, 50, or 70 mg/d administered for 1 year in Japanese children and adolescents with ADHD. LDX was associated with long‐term reductions in ADHD symptoms and severity.

Introduction Treatment for oligometastasis in prostate cancer has changed from systemic therapy to metastatic lesion‐targeted therapy. Early detection of metastatic lesions and assessment of the treatment response have become very important. Therefore, we started to perfume assessments with whole‐body magnetic resonance imaging, especially diffusion‐weighted imaging with background body signal suppression, as a modality to detect metastasis in patients with prostate cancer. Case presentation We encountered two cases of castration‐resistant prostate cancer in which oligometastasis was detected by diffusion‐weighted imaging with background body signal suppression. Metastasis‐directed therapy was initiated for to treat the lesions in each case. The treatment was effective for disease control and symptom relief. Diffusion‐weighted imaging with background body signal suppression could detect new lesions at an early phase and delineate changes in lesions immediately after therapy. Conclusion Diffusion‐weighted imaging with background body signal suppression enables early decision‐making for metastasis‐directed therapy compared with conventional imaging modalities. Further, metastasis‐directed therapy targeting oligometastatic lesions detected by diffusion‐weighted imaging with background body signal suppression may improve patients’ overall survival and quality of life.

Abstract Aim Although electroencephalogram (EEG) seizure duration and seizure threshold change during a course of electroconvulsive therapy, the mechanisms by which these factors influence heart rate during subsequent electroconvulsive therapy sessions are currently unclear. In the current study, we investigated changes in heart rate during electroconvulsive therapy. Methods We recorded electroencephalography and electrocardiography during electroconvulsive therapy in 12 patients with major depressive disorder. Baseline heart rate was defined as the mean heart rate in the 30 seconds prior to stimulus onset. The TimeMax peak refers to the maximum heart rate after stimulus onset. Time1/2 points represent the time points at which the heart rate had decreased to a value midway between the baseline heart rate and the TimeMax peak. We examined the relationships between EEG seizure duration, TimeMax, and Time1/2 throughout the course of electroconvulsive therapy. Results Time1/2 decreased as the number of electroconvulsive sessions increased. Time1/2 was positively correlated with EEG seizure duration. Conclusion The duration in which electroconvulsive therapy‐induced sympathetic nervous system activation returned halfway to baseline levels gradually shortened during the course of electroconvulsive therapy.

Abstract The clinical manifestations of COVID‐19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID‐19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID‐19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID‐19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID‐19 severity. Strikingly, we identified three distinct groups of markers (antiviral response‐related EV proteins, coagulation‐related markers, and liver damage‐related exRNAs) with the potential to serve as early predictive biomarkers for COVID‐19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID‐19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00‐1.00)). The validation set included 40 COVID‐19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73‐0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID‐19 therapy.

Abstract Acute kidney injury (AKI) causes glucose and protein metabolism abnormalities that result in muscle wasting, thereby affecting the long‐term prognosis of critical illness survivors. Here, we examined whether early intervention with treadmill exercise and branched‐chain amino acids (BCAA) can prevent AKI‐related muscle wasting and reduced physical performance in mice. Unilateral 15 min ischemia‐reperfusion injury was induced in contralateral nephrectomized mice, and muscle histological and physiological changes were assessed and compared with those of pair‐fed control mice, since AKI causes severe anorexia. Mice exercised for 30 min each day and received oral BCAA for 7 days after AKI insult. By day 7, ischemic AKI significantly decreased wet weight, myofiber cross‐sectional area, and central mitochondrial volume density of the anterior tibialis muscle, and significantly reduced maximal exercise time. Regular exercise and BCAA prevented AKI‐related muscle wasting and low physical performance by suppressing myostatin and atrogin‐1 mRNA upregulation, and restoring reduced phosphorylated Akt and PGC‐1α mRNA expression in the muscle. Ischemic AKI induces muscle wasting by accelerating muscle protein degradation and reducing protein synthesis; however, we found that regular exercise and BCAA prevented AKI‐related muscle wasting without worsening kidney damage, suggesting that early rehabilitation with nutritional support could prevent AKI‐related muscle wasting.