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Abstract Background Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used. Methods This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding). Results Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment. Conclusions Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

Abstract Background Acquired erythrocytosis can be classified into polycythemia vera (PV) and non‐neoplastic erythrocytosis (NNE). The vast majority of PV patients harbor JAK2 mutations, but differentiating JAK2 mutation‐negative PV from NNE is challenging due to a lack of definitive molecular markers. Methods We studied the clinical features of 121 patients with erythrocytosis of which 47 (38.8%) were JAK2 mutation‐positive and also fulfilled the diagnostic criteria for PV, and 67 (55.4%) JAK2 mutation‐negative erythrocytosis patients who were diagnosed as NNE. Diagnosis was strictly based on driver mutation analysis and central pathology review. Results No JAK2 mutation‐negative PV patients were found in our cohort. The NNE group showed significantly younger (p

Abstract A 40‐year‐old Japanese male presented with epigastric pain and loss of appetite at a general hospital three years ago. Computed tomography revealed massive thickening of the gastric wall, and gastroscopy revealed diffuse erythema and edematous thickening of the gastric mucosa. Thereafter, epigastric pain and gastric wall thickening recurred frequently, causing an inability to intake food. Conservative treatment was marginally effective; therefore, a distal gastrectomy was performed. Postoperatively, the patient resumed food intake without complications. Histopathological examination of the surgical specimen revealed Heinrich type 1 gastric ectopic pancreas (EP) with pancreatitis. In this case, the gastric wall's massive thickening was caused by gastric EP's pancreatitis. Although there are some reports of pancreatitis of gastric EP, there are no detailed reports of endoscopic findings, including endoscopic ultrasonography and the disease progression. Recurrent pancreatitis of EP leads to forming a septum within the gastric wall, resulting in a hematoma. Eventually, irreversible narrowing of the gastric lumen may occur, as observed in the present case. We consider this an important case report presenting detailed pathogenesis supported by endoscopic and pathohistological findings of surgical specimens. Our study will help in the early diagnosis and better management of the condition.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019, which has been a global pandemic. Since SARS-CoV-2 is transmitted through contaminated surfaces and aerosols, environmental disinfection is important to block the spread of the virus. Photocatalysts are attractive tools for virus inactivation and are widely used as air purifiers and coating materials. However, photocatalysts are inactive in the dark, and some of them need to be excited with light of a specific wavelength. Therefore, photocatalysts that can effectively inactivate SARS-CoV-2 in indoor environments are needed. Here, we show that a WO3 photocatalyst containing copper inactivated the SARS-CoV-2 WK-521 strain (Pango lineage A) upon irradiation with white light in a time- and concentration-dependent manner. Additionally, this photocatalyst also inactivated SARS-CoV-2 in dark conditions due to the antiviral effect of copper. Furthermore, this photocatalyst inactivated not only the WK-521 strain but also the Omicron variant BA.2. These results indicate that the WO3 photocatalyst containing copper can inactivate indoor SARS-CoV-2 regardless of the variant, in visible light or darkness, making it an effective tool for controlling the spread of SARS-CoV-2.

Although a previous autopsy series demonstrated that pulmonary leukemic infiltration (PLI) is a major pulmonary complication in patients with acute myeloid leukemia (AML), an antemortem diagnosis of PLI is rare. Diverse pulmonary complications cause acute respiratory failure (ARF) in patients with AML undergoing chemotherapy. This article reports two elderly patients with AML who presented with ARF due to PLI mimicking severe pneumonia during induction chemotherapy. Accurate antemortem diagnosis of PLI was almost impossible without pathological examination since the clinical course was not typical of PLI. We recommend considering PLI in patients with AML who have an unknown etiology of ARF.

Abstract Background The existing criteria for living kidney donors (LKDs)in Japan are controversial. We evaluated the roles of computed tomography volumetry (CTV) and 99 m Tc-diethylenetriamine penta-acetic acid (DTPA) scintigraphy in assessing preoperative and postoperative renal function and predicting early recovery of residual renal function. Methods We retrospectively reviewed the medical charts of 175 consecutive LKDs who underwent donor nephrectomy (DN) at our institution between 2006 and 2022. Preoperative renal volume was assessed using enhanced CTV, and screening of renal functions was performed using 99 m Tc-DTPA scintigraphy. We evaluated the estimated glomerular filtration rate (eGFR), single-kidney eGFR (skeGFR), and recovery rate three months after DN. Results We included 55 men and 81 women (median age, 59 years; median follow-up period, 73 months). Age > 60 years, hypertension, and total kidney volume/body surface area (TKV/BSA)

Abstract Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as ‘improved’, ‘stable’, and ‘deteriorated’. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials.

Introduction Patients with trisomy 13 have multiple malformations, including urological anomalies, and severe cognitive and psychomotor disabilities. We conducted a ureteroureterostomy for a mid‐ureteral stricture due to a retroiliac ureter in a patient with trisomy 13. Case presentation A 6‐month‐old girl with trisomy 13 developed a urinary tract infection. Computed tomography for assessing recurrent urinary tract infection revealed a left mid‐ureteral stricture due to the retroiliac ureter. At the age of 2, a ureteroureterostomy was performed. Two years after surgery, the urinary tract infection did not recur. Conclusion Ureteroureterostomy is a safe procedure for children with trisomy 13 and multiple comorbidities. Surgical treatment should be considered for patients with trisomy 13 when agreed upon by the family and comorbidities are well‐controlled.

Abstract. Background. Radical cystectomy (RC) is the standard surgical treatment for patients with muscle-invasive bladder cancer, but the prognosis is not favorable, and new prognostic factors need to be discovered. We investigated the potential of depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer who underwent RC. Furthermore, we examined the association between preoperative levels of circulating cell-free DNA and DOI. Materials and methods. We retrospectively reviewed patients who underwent RC between January 2007 and December 2017; those who received neoadjuvant chemotherapy were excluded. Depth of invasion was measured using hematoxylin-eosin–stained RC specimens. Results. Of the 121 patients selected, 41 (33.9%) were eligible for analysis. The median follow-up period was 14 months and mean DOI was 17 mm (range, 2–75 mm). Long DOI (>17 mm) was significantly associated with shorter progression-free survival (hazard ratio, 14.5; 95% confidence interval, 3.9–53.97, p < 0.0001) and cancer-specific survival (hazard ratio, 18.97; 95% confidence interval, 4.04–88.99, p = 0.0002) compared with short DOI. Multivariate analysis revealed that DOI was an independent risk factor for cancer-specific survival. The levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI (65 vs. 20 ng/mL, respectively; p = 0.028). Conclusions. Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.

Wheels and tires account for approximately 25% of the overall aerodynamic drag on a vehicle. Though researchers have investigated the accurate representation of rotating tires and wheels in aerodynamic simulations, they primarily focused on the differences in the tire or wheel geometry; few studies have investigated the effects of front-tire deflectors located at the bottom of passenger car bumpers. In other that deflectors can effectively reduce drag without significantly affecting design or packaging, deflector performance should be predicted at the early stages of product development. This study accordingly clarified the simulation conditions for full-vehicle aerodynamics necessary to accurately predict the performance of front-tire deflectors by simulating two different deflector configurations under four conditions comprising different degrees of tire geometry detail and wheel rotation methods. The simulation results were subsequently compared with wind tunnel test results, indicating that the numerical simulation using the least accurate tire geometry detail could not accurately predict the performance differences according to deflector configuration. However, the differences between the drag coefficients and airflow characteristics for each deflector were predicted more accurately by improving the tire geometry detail. The prediction accuracy was further improved by using the sliding mesh method instead of the boundary condition method to model the wheel rotation. Therefore, it was concluded that the detail tire geometry and wheel rotation method are important factors for improving the accuracy of front-tire deflector performance prediction.

Abstract Objectives To verify the effects of penile clamping on the degree of stress urinary incontinence and quality of life in post-radical prostatectomy patients. Results Thirty-seven patients suffering from stress urinary incontinence after undergoing radical prostatectomy were enrolled. A total of 19 and 18 patients were analyzed in the non-clamp and clamp groups, respectively. The mean ages of the patients in non-clamp and clamp groups were 68.3 ± 7.1 years and 71.2 ± 4.8 years, respectively; the mean time after radical prostatectomy was 28.9 ± 44.0 months and 26.2 ± 39.0 months, respectively. The penile clamp used was the CLAMPMED® (URINE CONTROL CLAMP) size M (MURANAKA MEDICAL INSTRUMENTS Co., Ltd.). Specific urinary care pads (Sawayaka Pad for Men, Small Quantity®, Unicharm Corporation), were provided; the average daily usage was monitored for four weeks. The quality of life was evaluated using the King’s Health Questionnaire. The average daily use of urinary care pads was significantly reduced in the clamp group than in the non-clamp group (-0.83 ± 1.51 vs. -0.16 ± 0.69, P = 0.0071). King’s Health Questionnaire scores did not change significantly in either group. Wearing the CLAMPMED® reduced the amount of urinary incontinence but did not improve the quality of life. Trial registration The Japan Registry of Clinical Trials (jRCT1052230083). Registered 2 August, 2023.

Objective: To compare the perioperative outcomes of patients with complex renal tumors treated with open versus robot-assisted partial nephrectomy. Methods: This retrospective study included 273 patients diagnosed with localized renal tumors at our institution between January 2007 and October 2020. Patients with moderate to high complexity tumors based on the RENAL nephrometry score were included. Perioperative outcomes were compared between open and robot-assisted partial nephrectomy patients. Remnant renal function was defined as the estimated glomerular filtration rate at 12 months after surgery. Results: Open and robot-assisted partial nephrectomy were performed in 43 and 77 patients, respectively. There was no significant difference in overall, cancer-specific, recurrence-free, and metastasis-free survival between the two groups. Remnant renal function was significantly better preserved in the open group, and body mass index was identified as an independent predictive factor (odds ratio 3.05, P = 0.017). Ischemia or type of surgery were not related to remnant renal function. The trifecta achievement rate was 51.2% in the open group and 71.4% in the robot-assisted group (P = 0.031), and the incidence of complications was significantly higher in the open partial nephrectomy group (P = 0.0030). Multivariate analysis revealed that open partial nephrectomy was an independent predictive factor for the incidence of complications (odds ratio 3.92, P = 0.0020). Conclusion: Robot-assisted partial nephrectomy can provide good and acceptable oncological and functional outcomes with fewer complications in patients with more complex renal tumors. Further research is needed to establish appropriate treatment strategies and guidelines in current clinical practice.

Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody–drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC.

Background: Phenylketonuria (PKU) is a rare inborn error of metabolism characterized by impaired catabolism of the amino acid phenylalanine (Phe) into tyrosine. Cross-sectional studies suggest slight alterations in cognitive performance and neural activation in adults with early-treated PKU. The influence of high Phe levels on brain function in adulthood, however, remains insufficiently studied. Therefore, we aimed to explore the effect of a four-week period of oral Phe administration − simulating a controlled discontinuation of Phe restriction and raising Phe to an off-diet scenario − on working memory-related neural activation and cerebral blood flow (CBF). Methods: We conducted a randomized, placebo-controlled, double-blind, crossover, non-inferiority trial to assess the effect of a high Phe load on working memory-related neural activation and CBF in early-treated adults with classical PKU. Twenty-seven patients with early-treated classical PKU were included and underwent functional magnetic resonance imaging (fMRI) of the working memory network and arterial spin labeling (ASL) MRI to assess CBF before and after a four-week intervention with Phe and placebo. At each of the four study visits, fMRI working memory task performance (reaction time and accuracy) and plasma Phe, tyrosine, and tryptophan levels were obtained. Additionally, cerebral Phe was determined by 1H-MR spectroscopy. Results: Plasma Phe and cerebral Phe were significantly increased after the Phe intervention. However, no significant effect of Phe compared to placebo was found on neural activation and CBF. Regarding fMRI task performance, a significant impact of the Phe intervention on 1-back reaction time was observed with slower reaction times following the Phe intervention, whereas 3-back reaction time and accuracy did not differ following the Phe intervention compared to the placebo intervention. Conclusion: Results from this present trial simulating a four-week discontinuation of the Phe-restricted diet showed that a high Phe load did not uniformly affect neural markers and cognition in a statistically significant manner. These results further contribute to the discussion on safe Phe levels during adulthood and suggest that a four-week discontinuation of Phe-restricted diet does not demonstrate significant changes in brain function.

Background. Photodynamic diagnosis-assisted transurethral resection of bladder tumors (PDD-TURBT) enhances detection of elusive lesions compared to standard white light-transurethral resection of bladder tumors (WL-TURBT). If minimal light exposure during PDD-TURBT induces the accumulation of reactive oxygen species (ROS), potentially resulting in phototoxicity in small lesions, apoptosis may be triggered in residual small tumors, allowing them to escape resection. We investigated the hypothesis of a potential photodynamic therapeutic effect during PDD-TURBT. Methods and Materials. Our study, conducted between January 2016 and December 2020 at Nara Medical University Hospital, focused on a specific emphasis on ROS production. Immunohistochemical analysis for thymidine glycol and Nε-hexanoyl-lysine was performed on 69 patients who underwent 5-aminolevulinic acid-mediated PDD-TURBT and 28 patients who underwent WL-TURBT. Additionally, we incrementally applied the minimal irradiation energy to T24 and UM-UC-3 cells treated with 5-aminolevulinic acid using instruments similar to those used in PDD-TURBT and evaluated intracellular ROS production and phototoxicity. Results. Immunohistochemical analysis revealed a significant increase in production of thymidine glycol and Nε-hexanoyl-lysine within the PDD-TURBT group. In T24 and UM-UC-3 cells treated with 5-aminolevulinic acid and light exposure, immunofluorescent staining demonstrated a dose-dependent increase in intracellular ROS production. In addition, higher irradiation energy levels were associated with a greater increase in ROS production and phototoxicity, as well as more significant decrease in mitochondrial membrane potential. Conclusion. Although the irradiation energy used in PDD-TURBT did not reach the levels commonly used in photodynamic therapy, our findings support the presence of a potential cytotoxic effect on bladder lesions during PDD-TURBT.

Background. Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow-up of nonmuscle invasive bladder cancer is recommended, its necessity remains invalidated. A single-institute long-term follow-up cohort study to evaluate the clinical impact of routine surveillance imaging and identify risk factors for upper urinary tract urothelial cancer recurrence after nonmuscle invasive bladder cancer treatment was conducted. Methods and Materials. A retrospective chart review of 864 patients with primary nonmuscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. The opportunities to diagnose its recurrence were examined. Moreover, oncological outcomes included upper urinary tract urothelial cancer recurrence-free survival and overall survival. Results. Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. Among 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in 2 (10.5%), urine cytology in 2 (10.5%), and presence of gross hematuria in 1 (5.3%). All patients had high- or highest-risk NMIBC at diagnosis of primary nonmuscle invasive bladder cancer. On multivariate Fine-Gray proportional regression analyses, a tumor size of ≥30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence-free survival (P=0.040 and 0.0089, respectively). Conclusion. Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with nonmuscle invasive bladder cancer accompanied by a tumor size of ≥30 mm and carcinoma in situ.

Abstract Objective To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil in Japanese men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with dutasteride. Results Twenty-four patients were enrolled. The participants had a median age of 71.0 (64.8–73.0) years and a median prostate volume of 37.3 (29.7–41.8) mL as measured using transabdominal sonography. The efficacy indicators, such as International Prostate Symptom Score (IPSS), quality of life (QOL) score, night-time urinary frequency, and night-time maximum voided volume, improved significantly at 4 weeks, and the effects lasted until 24 weeks (IPSS: 9.5 vs. 17.0, QOL: 2.0 vs. 4.0, nocturia: 2.0 vs. 2.0, night-time maximum voided volume: 290.0 vs. 240.0 mL). Overactive bladder symptom score (OABSS) and sexual health inventory for men (SHIM) significantly improved at 12 weeks, and the effects lasted until 24 weeks (OABSS: 3.0 vs. 5.0, SHIM: 11.0 vs. 7.5). However, maximum urine flow and residual urine volume showed no improvement at any point. Adverse events occurred in two cases. Taken together, add-on therapy with tadalafil was effective for patients with LUTS/BPH resistant to dutasteride monotherapy. In addition, this therapy was not associated with severe adverse events.