1.Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-
Joonbeom KWON ; Duk Yoon KIM ; Kang Jun CHO ; Mamoru HASHIMOTO ; Kanako MATSUOKA ; Tadanobu KAMIJO ; Zhou WANG ; Sergei KARNUP ; Anne M. ROBERTSON ; Pradeep TYAGI ; Naoki YOSHIMURA
International Neurourology Journal 2024;28(Suppl 1):12-33
Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.
2.Association between Aortic Calcification Burden and the Severity of Erectile Dysfunction in Men Undergoing Dialysis: A Cross-Sectional Study
Naoki FUJITA ; Shingo HATAKEYAMA ; Masaki MOMOTA ; Yuki TOBISAWA ; Tohru YONEYAMA ; Teppei OKAMOTO ; Hayato YAMAMOTO ; Takahiro YONEYAMA ; Yasuhiro HASHIMOTO ; Kazuaki YOSHIKAWA ; Chikara OHYAMA
The World Journal of Men's Health 2023;41(2):373-381
Purpose:
Accelerated atherosclerosis is a major complication in patients with end-stage renal disease and it plays an important role in the pathogenesis of erectile dysfunction (ED). However, the association between aortic calcification burden and the severity of ED remains unclear. The aim of the present study was to investigate this association in men undergoing dialysis.
Materials and Methods:
This cross-sectional study included 71 men undergoing peritoneal dialysis and/or hemodialysis between July 2016 and May 2018 at Mutsu General Hospital. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Aortic calcification index (ACI) was examined as a clinical indicator of abdominal aortic calcification. Multivariable logistic regression analysis was performed to identify the significant factors associated with severe ED.
Results:
The median age of the study participants was 64 years; all had ED, with 64.8% having severe ED. In the multivariable analyses, a slight association was observed between ankle-brachial index and severe ED (odds ratio [OR], 0.058; p=0.072), whereas ACI was significantly associated with severe ED (OR, 1.022; p=0.022).
Conclusions
Aortic calcification burden was independently associated with severe ED.
3.Association between Advanced Glycation End-Products, Carotenoids, and Severe Erectile Dysfunction
Naoki FUJITA ; Mizuri ISHIDA ; Takuro IWANE ; Hiroyuki SUGANUMA ; Mai MATSUMOTO ; Shingo HATAKEYAMA ; Takahiro YONEYAMA ; Yasuhiro HASHIMOTO ; Tatsuya MIKAMI ; Ken ITOH ; Chikara OHYAMA
The World Journal of Men's Health 2023;41(3):701-711
Purpose:
To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men.
Materials and Methods:
This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations.
Results:
The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels.
Conclusions
Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.
4.Can Erectile Dysfunction Severity Predict Major Adverse Cardiovascular Events in Men Undergoing Dialysis? A Prospective Cohort Study
Naoki FUJITA ; Masaki MOMOTA ; Yusuke OZAKI ; Yuki TOBISAWA ; Tohru YONEYAMA ; Teppei OKAMOTO ; Hayato YAMAMOTO ; Shingo HATAKEYAMA ; Takahiro YONEYAMA ; Yasuhiro HASHIMOTO ; Kazuaki YOSHIKAWA ; Chikara OHYAMA
The World Journal of Men's Health 2023;41(4):900-908
Purpose:
To evaluate the impact of severe erectile dysfunction (ED) on future major adverse cardiovascular events (MACE) in men on dialysis.
Materials and Methods:
This prospective cohort study included 71 men on dialysis. ED was assessed using the Sexual Health Inventory for Men (SHIM). Men were divided into the mild/moderate ED (SHIM score ≥8) and severe ED (SHIM score ≤7) groups. The primary endpoint was MACE-free survival. MACE was a composite of myocardial infarction, cardiovascular death, and stroke. The secondary endpoints were cardiac event-free survival and overall survival (OS). Moreover, the predictive abilities of severe ED for 5-year MACE, 5-year cardiac events, and 5-year overall mortality were evaluated.
Results:
The median age and follow-up period of the included men were 64 years and 58 months, respectively. The median SHIM score was 4.0; all had a degree of ED, and 64.7% had severe ED. In the background-adjusted multivariable analyses, severe ED was not significantly associated with shorter MACE-free survival (hazard ratio [HR], 1.890; 95% confidence interval [CI], 0.533–6.706; p=0.324), cardiac event-free survival (HR, 2.081; 95% CI, 0.687–6.304; p=0.195), and OS (HR, 0.817; 95% CI, 0.358–1.863; p=0.630). Severe ED did not significantly improve the predictive abilities for 5-year MACE, 5-year cardiac events, and 5-year overall mortality (p=0.110, p=0.101, and p=0.740, respectively).
Conclusions
ED severity was not associated with shorter MACE-free survival, cardiac event-free survival, or OS, and ED severity could not improve the predictive abilities for these outcomes in men undergoing dialysis.
5.A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer
Tadayuki TAKAGI ; Mitsuru SUGIMOTO ; Hidemichi IMAMURA ; Yosuke TAKAHATA ; Yuki NAKAJIMA ; Rei SUZUKI ; Naoki KONNO ; Hiroyuki ASAMA ; Yuki SATO ; Hiroki IRIE ; Jun NAKAMURA ; Mika TAKASUMI ; Minami HASHIMOTO ; Tsunetaka KATO ; Ryoichiro KOBASHI ; Yuko HASHIMOTO ; Goro SHIBUKAWA ; Shigeru MARUBASHI ; Takuto HIKICHI ; Hiromasa OHIRA
Clinical Endoscopy 2023;56(1):107-113
Background/Aims:
Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC.
Methods:
A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018–2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA.
Results:
No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation.
Conclusions
EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.
6.Case Report of a COVID-19 Sub-acute Patient with Rehabilitation Therapy
Kazumi KASHIWABARA ; Toru TAKEKAWA ; Midori HAMA ; Naoki YAMADA ; Shu WATANABE ; Gentaro HASHIMOTO ; Masahiro ABO ; Kyota SHINFUKU
The Japanese Journal of Rehabilitation Medicine 2022;():20064-
COVID-19 spread from Wuhan City, People's Republic of China, in December 2019, followed by an explosion of infections worldwide. The number of infected people has also risen dramatically in Japan and has become a major social problem. Patients with severe disease require a long period to return to society due to significant physical weakness even after recovery. We report a patient in his 40s with a history of nephrectomy who was infected with COVID-19 and became critically ill.After being diagnosed with COVID-19 by PCR test, the patient was admitted to our hospital. His respiratory status rapidly worsened and he was temporarily managed by ECMO in the intensive care unit. At the time of his first contact with us (day 31 post-hospitalization), he was unable to hold himself in a standing position for a long time and required a walker. Initially, from the perspective of preventing the spread of infection, we instructed him in self-directed training rather than individual therapy. From day 49, he began to receive physical therapy. He was discharged on day 53 with independence in outdoor walking. He was instructed to consume protein after exercising and he was managed on an outpatient basis. He returned to work. His skeletal muscle mass increased by BIA and his respiratory and motor functions were restored.He received instructions on recovering from severe illness after COVID-19 infection, which focused on nutrition, voluntary training, and monitored individual therapy in accordance with rehabilitation therapy. He was able to return to society with no sequelae.
7.Open Abdominal Management Among Non-Trauma Patients: The Appropriate Duration and a New Clinical Index
Koichi INUKAI ; Akihiro USUI ; Yu HASHIMOTO ; Fumitaka KATO ; Koji AMANO ; Hiroyuki KAYATA ; Nobutaka MUKAI ; Naoki SHINYAMA
Journal of Acute Care Surgery 2022;12(3):97-102
Purpose:
Despite widespread adoption of open abdominal management (OAM), there is currently no threshold criterion for OAM duration for non-trauma patients. Moreover, there is a positive relationship between morbidity and the duration of OAM, but an uncertain relationship with patients’ age. Therefore, a novel clinical index for the duration of open abdominal management (IDOM) was developed based on the patient’s age and risk of severe complications following OAM to indicate the maximum tolerable number of days of OAM based on the individual’s age. The utility of this new index was evaluated.
Methods:
This retrospective study included 65 non-trauma patients managed with an open abdomen (OA) from August 2015 to August 2018. The IDOM was developed based on the patient’s age. The result indicated the maximum number of OA days. Patients’ demographic and operative variables were examined and patient data was assigned to one of two groups according to whether the actual number of OA days was above or below the calculated IDOM. Prevalence of complications between these groups was compared. Measures of validity were employed to assess the utility of the IDOM for patient complications.
Results:
Sixty-five patients were included. The above-the calculated IDOM group exhibited a significantly longer OA and higher rates of wound complications and postoperative respiratory complications compared with the below the calculated IDOM group. The IDOM predicted the incidence of OA-related complications with a sensitivity of 72.4%, and a specificity of 80.6%.
Conclusion
The IDOM is a potentially useful tool for appropriate duration at the outset of OA.
8.Case Report of a COVID-19 Sub-acute Patient with Rehabilitation Therapy
Kazumi KASHIWABARA ; Toru TAKEKAWA ; Midori HAMA ; Naoki YAMADA ; Shu WATANABE ; Gentaro HASHIMOTO ; Masahiro ABO ; Kyota SHINFUKU
The Japanese Journal of Rehabilitation Medicine 2022;59(3):329-336
COVID-19 spread from Wuhan City, People's Republic of China, in December 2019, followed by an explosion of infections worldwide. The number of infected people has also risen dramatically in Japan and has become a major social problem. Patients with severe disease require a long period to return to society due to significant physical weakness even after recovery. We report a patient in his 40s with a history of nephrectomy who was infected with COVID-19 and became critically ill.After being diagnosed with COVID-19 by PCR test, the patient was admitted to our hospital. His respiratory status rapidly worsened and he was temporarily managed by ECMO in the intensive care unit. At the time of his first contact with us (day 31 post-hospitalization), he was unable to hold himself in a standing position for a long time and required a walker. Initially, from the perspective of preventing the spread of infection, we instructed him in self-directed training rather than individual therapy. From day 49, he began to receive physical therapy. He was discharged on day 53 with independence in outdoor walking. He was instructed to consume protein after exercising and he was managed on an outpatient basis. He returned to work. His skeletal muscle mass increased by BIA and his respiratory and motor functions were restored.He received instructions on recovering from severe illness after COVID-19 infection, which focused on nutrition, voluntary training, and monitored individual therapy in accordance with rehabilitation therapy. He was able to return to society with no sequelae.
9.Quantitative Resting State Electroencephalography in Patients with Schizophrenia Spectrum Disorders Treated with Strict Monotherapy Using Atypical Antipsychotics
Takashi OZAKI ; Atsuhito TOYOMAKI ; Naoki HASHIMOTO ; Ichiro KUSUMI
Clinical Psychopharmacology and Neuroscience 2021;19(2):313-322
Objective:
The effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients.
Methods:
Data from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients.
Results:
We included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power.
Conclusion
Use of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.
10.Quantitative Resting State Electroencephalography in Patients with Schizophrenia Spectrum Disorders Treated with Strict Monotherapy Using Atypical Antipsychotics
Takashi OZAKI ; Atsuhito TOYOMAKI ; Naoki HASHIMOTO ; Ichiro KUSUMI
Clinical Psychopharmacology and Neuroscience 2021;19(2):313-322
Objective:
The effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients.
Methods:
Data from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients.
Results:
We included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power.
Conclusion
Use of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.


Result Analysis
Print
Save
E-mail