Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.

Health Effects of Electrolyzed Hydrogen Water for the Metabolic Syndrome and Pre-Metabolic Syndrome: A 3-Month Randomized Controlled Trial and Subsequent Analyses.

We studied the effect of three months' use of electrolyzed hydrogen water (EHW, Electrolyzed Hydrogen Water conditioner produced by Nihon Trim Co., Ltd.) on metabolic and pre-metabolic syndrome groups. This research was carried out jointly by Susaki City; Nihon Trim Co., Ltd.; and Kochi University as part of a local revitalization project with health as a keyword. A randomized, placebo-controlled, double-blind, parallel-group trial was conducted to evaluate the clinical impact of EHW on participants who suffered from metabolic syndrome or pre-metabolic syndrome. EHW was produced via electrolysis using a commercially available apparatus (Nihon Trim Co., Ltd., Osaka, Japan). During exercise, oxidative stress increases, and active oxygen species increase. In this study, we examined 181 subjects with metabolic syndrome or pre-metabolic syndrome. Among the group that drank EHW for 3 months, those who also engaged in a high level of physical activity showed a significant difference in waist circumference reduction. Although no significant difference was observed, several positive results were found in the participants who engaged in a high level of physical activity. Urinary 8-OHdG, urinary nitrotyrosine, HbA1c, and blood glucose levels increased in the filtered water (FW) group but decreased in the EHW group. High-sensitivity CRP increased less in the EHW group. 8-Isoprostane decreased more in the EHW group. In subgroup analysis, the EHW group showed a significantly greater reduction in waist circumference than the FW group only when controlled for high physical activity. Based on the result, we suggest that, among participants in the study who suffered from metabolic syndrome and pre-metabolic syndrome in which the level of active oxygen species is said to be higher than in healthy subjects, the group that consumed EHW and also engaged in a high level of physical activity experienced a suppressed or reduced increase in active oxygen species.

Cerebrospinal Fluid Refill Test as a Novel Diagnostic Tool for Cerebrospinal Fluid Hypovolemia: Preliminary Result.

OBJECTIVE: Cerebrospinal fluid (CSF) hypovolemia presents with orthostatic headaches due to CSF leakage. However, a direct association between the lack of CSF and clinical symptoms has not been found. CSF hypovolemia can be improved by refilling CSF. Therefore, we assessed the validity of a CSF refill test. METHODS: From November 2019 to August 2021, we included 10 patients (≥18 years old) with potential CSF hypovolemia, clear orthostatic headaches, and a CSF opening pressure <10 cmH2O. In the CSF refill test, 10 mL of artificial CSF was injected intrathecally. The primary outcome was improvement in orthostatic headache assessed using a visual analog scale (VAS), while the secondary outcomes were the 10-m walk time and adverse events. When the symptoms temporarily improved after intrathecal injection, the patients underwent radiologic imaging to identify the CSF leak, and an epidural blood patch was proposed accordingly. RESULTS: All patients showed post-test improvements in the VAS score (median [interquartile range], pretest 63.0 [50.3-74.3] vs. post-test 1.5 [0.0-26.0]). The 10-m walk time also significantly improved (9.5 [8.5-10.2] s vs. 8.2 [7.9-8.7] s). One patient experienced temporary right leg numbness associated with a lumbar puncture. After radiologic investigation, 9 patients underwent epidural blood patches, of which 6 were completely cured, and 3 revealed partial improvement. CONCLUSIONS: The cerebrospinal fluid (CSF) refill test was safe and effective in demonstrating the direct association between the lack of CSF and clinical symptoms and may help predict the outcome of an epidural blood patch.

Questionnaire survey on the conceptual framework, optimal evaluation, and support measures for children's language disorders in Japan using the Delphi method.

Objectives: To compile the opinions of native Japanese speakers on the conceptual framework, optimal evaluation, and support measures for children with language disorders to devise materials on which a consensus can be formed. Design: A quantitative descriptive study using the Delphi method. Setting: Using the Delphi method, 43 clinicians with at least 15 years of experience working professionally with children's language disorders in Japan were surveyed three times via a web-based questionnaire. Thirty-nine items that were carefully selected by the working group were surveyed, and the agreement level was set to ≥80%. Main Outcome Measures: We investigated the following aspects related to developmental language disorder (DLD) among Japanese children: definition, core symptoms, evaluation of core symptoms, relationship with a second language, relationship with other related disorders, support systems, and information availability. Results: Overall, 43 qualified panel members were included in this study. Among the 39 items in the questionnaire, a high level of consensus (≥80%) from the responses of the participants was achieved for five items in Round 1, whereas no consensus (<50%) was achieved for seven items. After revising and integrating the questionnaires into 22 items, we conducted Rounds 2 and 3 and obtained high and medium levels of agreement in 20 items on disease concept, core symptoms, coexisting disorders, and manner of support of DLD in children. Conclusion: Our results clarify the previously ambiguous image of DLD in Japan. Information-sharing strategies that connect professionals, patients, their families, and community members are required in the future. Level of Evidence: 5.

Vibegron 50 mg Once Daily Improves OABSS, OAB-q SF Score in OAB Patients ≥80 Years Old in Real-World Clinical Settings and Switching from Other OAB Drugs May Reduce Residual Urine Volume.

Objective: The treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group. Methods: This multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥3 and OABSS question 3 score ≥2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit. Results: Of the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered. Conclusion: Vibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.

What is the optimal range of glycemic control for non-diabetic patients undergoing gastroenterological surgery? A single-center randomized controlled trial using an artificial pancreas.

BACKGROUND: This study aimed to determine the optimal target range of perioperative glycemic control for gastroenterological surgery. A closed-loop-type artificial pancreas (AP) was used to diminish the negative impact of hypoglycemia and glycemic variability during tight glycemic control. METHODS: In this single-center randomized trial, non-diabetic patients were assigned to tight (80-110 mg/dL) or moderate glycemic control (110-140 mg/dL) groups between August 2017 and May 2021. AP was used from the intraoperative period until discharge from the intensive care unit. The primary endpoint was the serum interleukin (IL)-6 level on the third postoperative day (3POD), and the secondary endpoints included clinical outcomes. RESULTS: Recruitment was closed before reaching the planned number of patients due to slow enrollment. Tight glycemic control (n = 62) resulted in lower mean glucose levels than moderate glycemic control (n = 66) (121.3 ± 10.8 mg/dL vs. 133.5 ± 12.0 mg/dL, p < 0.001). Insulin was administered at a 65% higher rate for tight glycemic control, achieving appropriate glucose control more than 70% of the treatment time. No hypoglycemia occurred during the AP treatment. No significant difference was observed in serum IL-6 levels on 3POD (23.4 ± 31.1 vs. 32.1 ± 131.0 pg/mL, p = 0.64), morbidity rate, surgical mortality rate, or length of hospital stay between the two groups. CONCLUSIONS: Clinically relevant short-term results did not differ, implying that 80-110 and 110-140 mg/dL are permissible glycemic control ranges when using AP in non-diabetic patients undergoing gastroenterological surgery. (Registered in UMIN; UMIN000028036).

A retrospective investigation to establish new screening approach for the detection of patients at high risk of Fabry disease in male left ventricular hypertrophy patients.

BACKGROUND: The prevalence of Fabry disease (FD) in male patients with left ventricular hypertrophy (LVH) is about 1%. From the perspective of performing more efficient screening with measurement of α-galactosidase (α-Gal) activity, it is important to raise the pretest probability. METHODS: We retrospectively investigated the prevalence of FD in 701 male patients with LVH who already had been screened by measurement of α-Gal activity in eight hospitals. From the viewpoint of enzymatic screening, we validated previously reported clinical features of FD including the electrocardiographic and echocardiographic characteristics with comparing each clinical determinant between patients with FD and non-FD patients. We finally aimed to establish a new screening approach for the detection of patients at high risk of FD. RESULTS: There were five FD patients (0.7%) in the 701 male patients with LVH. Those five patients with FD all had the cardiac variant type and age at detection of LVH was ≥35 years in all patients. In LVH patients with LV ejection fraction (EF) ≥ 50%, Pend-Q interval < 40 msec, SV1 + RV5 > 4.0 mV, and diffuse LVH were important determinants of FD. In LVH patients with LVEF < 50%, asymmetric septal hypertrophy and posterior wall motion abnormality seemed to be associated with FD. CONCLUSIONS: In our retrospective study, the prevalence of FD in male patients with LVH was found to be 0.7%. We established the efficient combinations of clinical determinants using age at detection of LVH, Pend-Q interval, high voltage, and LVH pattern in an echocardiogram.

Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study).

OBJECTIVES: Transurethral resection of bladder tumor with photodynamic diagnosis has been reported to result in lower residual tumor and intravesical recurrence rates in non-muscle invasive bladder cancer. We aimed to evaluate the usefulness of photodynamic diagnosis-transurethral resection of bladder tumor combined with oral 5-aminolevulinic acid hydrochloride for high-risk non-muscle invasive bladder cancer. METHODS: High-risk non-muscle invasive bladder cancer patients with an initial photodynamic diagnosis-transurethral resection of bladder tumor (photodynamic diagnosis group) were prospectively registered between 2018 to 2020. High-risk non-muscle invasive bladder cancer cases with a history of initial white-light transurethral resection of bladder tumor (white-light group) were retrospectively registered. Propensity score-matching analysis was used to compare residual tumor rates, and factors that could predict residual tumors at the first transurethral resection of bladder tumor were evaluated. RESULTS: Analyses were conducted with 177 and 306 cases in the photodynamic diagnosis and white-light groups, respectively. The residual tumor rates in the photodynamic diagnosis and white-light groups were 25.7% and 47.3%, respectively. Factor analysis for predicting residual tumors in the photodynamic diagnosis group showed that the residual tumor rate was significantly higher in cases with a current/past smoking history, multiple tumors, and pT1/pTis. When each factor was set as a risk level of 1, cases with a total risk score ≤1 showed a significantly lower residual tumor rate than cases with a total risk score ≥2 (8.3% vs 33.3%, odds ratio 5.46 [1.81-22.28]). CONCLUSIONS: In high-risk non-muscle invasive bladder cancer cases, the odds of a residual tumor after initial photodynamic diagnosis-transurethral resection of bladder tumor were 0.39-fold that of the odds of those after initial white-light transurethral resection of bladder tumor. A risk stratification model could be used to omit the second transurethral resection of bladder tumor in 27% of the cases.

Tadalafil 5 mg Once Daily Improved Each IPSS Subscore, QOL, and Nocturia in Elderly BPH Patients over 70 Years Old in a Real-World Clinical Setting.

OBJECTIVE: No reports have evaluated the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. The present study aimed to evaluate the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. We therefore divided patients into 2 groups about the age of 70 years and investigated the treatment effects of tadalafil regarding voiding and storage functions by age group. METHODS: Changes from baseline in each parameter (International Prostate Symptom Score [IPSS], quality of life [QOL] score, Overactive Bladder Symptom Score [OABSS], and residual urine volume) at 4, 12, and 24 weeks after initiating tadalafil for benign prostatic hyperplasia (BPH) patients were compared between groups (50-69 years vs. ≥70 years). In addition, side effects of tadalafil were investigated by age group. RESULTS: In the 50-69 years group, significant improvements from baseline were seen in IPSS total and QOL score for all time points. In addition, significant improvements in IPSS storage subscore from baseline were observed at the 4- and 24-week time points. In the ≥70 years group, significant improvements from baseline were seen in IPSS total, IPSS voiding and storage subscores, and QOL score at each time point. CONCLUSIONS: Tadalafil 5 mg once daily appeared effective in clinical settings for elderly BPH patients even over 70 years old.

The safety of early versus late ileostomy reversal after low anterior rectal resection: a retrospective study in 47 patients.

BACKGROUND: This study aimed to clarify the safety of early closure in diverting ileostomy with lower anterior rectal-cancer resection. METHODS: We retrospectively reviewed consecutive 47 patients who underwent diverting ileostomy with lower rectal-cancer resection between May 2009 and October 2017. The results of the stoma closure were compared between patients who underwent stoma closure within 90 days (early closure [EC] group) and those who underwent late closure (LC group; closure after 90 days). Because of the small sample size, the frequency of severe complications post closure was analyzed. RESULTS: Among 47 patients, 29 were in the EC group. Postoperative complications occurred in 48.3% (14/29) and 27.8% (5/18) of patients in the EC and LC groups, respectively. This difference was due to minor complications (Clavien-Dindo Classification I/II), such as superficial incisional surgical site infections (n=5) in the EC group. The rate of severe complications (Clavien-Dindo Classification ≥ III) was similar between the groups (20.7% vs. 16.7%, p=1, Fisher's exact test). CONCLUSIONS: No association was observed between the time of closure and development of major complications; however, there was an increased likelihood of minor complications after EC. This study provides a basis on which future treatment guidelines for early stoma closure may be developed without affecting patient quality of life.

Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method.

PURPOSE: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method. METHODS: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching. RESULTS: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings. CONCLUSION: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

Influence of nutrition support therapy on readmission among patients with acute heart failure in the intensive care unit: A single-center observational study.

BACKGROUND & AIMS: The effect of nutrition support therapy on prevention of readmission among patients with acute heart failure (HF) in an intensive care unit (ICU) setting remains unclear. We hypothesized that nutrition support therapy might decrease the readmission rate among these patients. Thus, we conducted a single-center prospective observational study to verify this hypothesis. METHODS: Patients diagnosed with acute HF admitted to the ICU for more than 14 days between April 2016 and March 2017 were included in the analysis. The primary outcome was the relationship between nutritional intake and HF-related hospital readmission due to HF at 180 days after discharge. We divided the participants into 2 groups: patients who were not readmitted to hospital within 180 days after discharge (non-readmission group) and patients who were readmitted within this timeframe (HF-related readmission group). Data were expressed as median (interquartile range). RESULTS: Sixty patients required readmission due to HF-related events (HF-related readmission group). On the other hand, 127 patients did not require readmission (non-readmission group). The calorie and protein intake on day 3 after ICU admission in the HF-related readmission group was significantly higher than that in the non-readmission group [20.5 (14.2, 27.8) vs. 27.7 (22.5, 31.2) kcal/kg/day, p < 0.001; 0.7 (0.5, 0.9) vs. 0.9 (0.7, 1.2) g/kg/day, p < 0.001, respectively]. Similarly, the protein intake values on day 7 were also significantly higher in the HF-related readmission group [0.8 (0.6, 1.0) vs. 0.9 (0.7, 1.2) g/kg/day, p = 0.04]. Multivariate analysis indicated that total caloric intake on day 3 was an independent factor affecting readmission (odds ratio = 1.05, 95% confidence interval = 1.01-1.09, p = 0.006). In addition, when the cut off value of calorie intake was set to 18 kcal/kg/day, the group ingesting ≥18 kcal/kg/day on day 3 had a significantly higher readmission rate within 180 days after discharge. CONCLUSIONS: Our data showed that total calorie intake ≥18 kcal/kg/day on day 3 might increase the readmission rate among patients with acute HF.

Evaluation of offset of conjunctival hyperemia induced by a Rho-kinase inhibitor; 0.4% Ripasudil ophthalmic solution clinical trial.

Glaucoma leads to irreversible blindness. Numerous anti-glaucoma eye drops have been developed. Unfortunately, many patients with glaucoma still suffer from progressive visual disorders. Recently, ripasudil hydrochloride hydrate, a selective Rho-associated protein kinase inhibitor, was launched for the treatment of glaucoma. However, adverse events, such as conjunctival hyperemia, are often noted in clinical trials using healthy subjects. Therefore, we investigated the onset, offset, and kinetic changes of conjunctival hyperemia induced by ripasudil ophthalmic solution in patients with open-angle glaucoma or ocular hypertension who had already been treated with anti-glaucoma eye drops other than ripasudil. Conjunctival hyperemia was evaluated by both clinical grading by 3 ophthalmic physicians and pixel coverage of conjunctival blood vessels determined by conjunctival hyperemia-analyzing software. Conjunctival hyperemia appeared within 10 min post-instillation in most of the participants. Clinical grade and pixel coverage increased significantly 10 min post-instillation and then decreased. In most of the participants, hyperemia resolved within 2 h. Median conjunctival hyperemia offset was 90 min. A tendency of monotonic increase was observed between clinical grade and pixel coverage. Taken altogether, hyperemia induced by ripasudil was transient in glaucoma patients who had already been treated with anti-glaucoma eye drops other than ripasudil.