Kochi Medical School Hospital

5-Aminolevulinic acid (5-ALA) reportedly improves overactive bladder (OAB) symptoms by reducing reactive oxygen species derived from vascular endothelial cells to protect vascular function and enhance bladder blood flow and by inhibiting bladder C-fiber activity. This double-blind, randomized controlled trial aimed to evaluate the efficacy and safety of 5-ALA in participants with OAB. This randomized, prospective study classified the participants into the 5-ALA and placebo groups. The 5-ALA group received oral 5-ALA phosphate at 150mg/day for 12weeks. The efficacy of 5-ALA was determined by assessing the changes in the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire Short Form from baseline to weeks 4 and 12 after treatment initiation, as well as the post-void residual urine volume. Regarding safety, we evaluated participants' blood pressure and adverse events. This study enrolled and randomized 49 participants, with 23 in the 5-ALA group and 26 in the placebo group. Ultimately, 47 participants completed the study (21 and 26 in the 5-ALA and placebo groups, respectively). From baseline to week 12, OABSS significantly decreased from 8.81 to 6.52 (- 2.29) in the 5-ALA group and from 8.54 to 6.35 (- 2.35) in the placebo group (both: p = 0.008). However, no significant difference was noted between the two groups at week 12 (p = 0.956). Using a mixed model for repeated measures with a random intercept, the model-adjusted between-group difference in the change from baseline to week 12 in the OABSS between the 5-ALA and placebo groups was 0.06 points (95% confidence interval, - 1.63 to 1.75; p = 0.944). This study found no significant improvement in OAB symptoms with 5-ALA administration. Nevertheless, given that no previous double-blind, randomized controlled trial has assessed 5-ALA's efficacy in patients with OAB, this study holds important value as a pilot study. This study was prospectively registered in the Japan Registry of Clinical Trials (jRCT); registration number: jRCTs061220050; registration date: [August 29, 2022].

In hepatocellular carcinoma (HCC), molecularly targeted therapies have been the major focus of recent research. In this study, we evaluated the clinical and biological roles of tumor necrosis factor superfamily 4 (TNFSF4), an inflammatory cytokine, as a therapeutic target in HCC. Using a bioinformatics approach, we identified TNFSF4 as a candidate driver in HCC and assessed the prognostic significance of TNFSF4. Its biological role in HCC was clarified through in vitro experiments, such as cell cycle/colony formation assays, using TNFSF4-overexpressing HCC cells. Moreover, a candidate repositioned drug was identified from public drug sensitivity data, and its antitumor effects and mechanisms were examined both in vitro and in vivo. Analysis of The Cancer Genome Atlas datasets for HCC revealed that TNFSF4 was overexpressed in HCC cells owing to increased DNA copy numbers. Additionally, high TNFSF4 expression was significantly associated with poorer prognosis. Immunohistochemical staining showed that TNFSF4 was overexpressed in the cytoplasm of tumor cells. In vitro analysis showed that TNFSF4 overexpression promoted the G1/S transition in the cell cycle, stimulated proliferation, and increased phosphoinositol-3-kinase (PI3K) phosphorylation, resulting in p21 downregulation and enhanced Rb phosphorylation. In bioinformatics-based drug repositioning analysis, fluspirilene, a typical antipsychotic agent, was identified as a repositioned drug that inhibited HCC growth through cyclin D1 suppression, downstream of TNFSF4. TNFSF4 was a candidate driver and a prognostic biomarker, promoting HCC progression by activating the PI3K/Akt signaling pathway. Furthermore, fluspirilene may have applications as a repositioned drug for HCC with high TNFSF4 expression.

ABSTRACTIntroductionWe report the case of a patient with severe uterine prolapse who underwent successful vaginal pessary removal after pelvic floor muscle training.Case PresentationA 63‐year‐old woman presented with urinary dysfunction and residual urine. She was diagnosed with stage III pelvic organ prolapse by an obstetrician‐gynecologist, and a vaginal pessary was inserted. The patient underwent pelvic floor muscle training for 4 months while the vaginal pessary remained in situ. M‐mode ultrasonography revealed improved pelvic floor function, necessitating vaginal pessary removal. The patient's uterine prolapse improved to pelvic organ prolapse‐quantification stage II without recurrence of pelvic organ prolapse, urinary dysfunction, or residual urine after 2 years.ConclusionsIn patients with severe uterine prolapse who use a vaginal pessary, appropriate pelvic floor muscle training guided by a physical therapist may eliminate the need for continued pessary use.

Background and Aims: Although combined general anesthesia and epidural analgesia are used in open surgery to promote rehabilitation and expectoration, as well as to prevent postoperative pulmonary complications, their effect in thoracoscopic esophagectomy remains unclear. This study aimed to address this issue. Patients and Methods: We enrolled 150 patients who underwent thoracoscopic esophagectomy between May 2017 and July 2025. Patient characteristics and postoperative outcomes, including maximum numerical rating scale (NRS) after surgery and pneumonia, were compared between the use and non-use of epidural analgesia. Epidural analgesia was not administered in patients using antithrombotic/anticoagulant drugs or in those with a history of thoracic spine surgery. Postoperative analgesia involved the scheduled administration of acetaminophen in all cases, with patient-controlled analgesia using opioids administered to the non-epidural analgesia group. Results: Epidural analgesia was administered to 113 patients (75.3%). The most common levels of epidural catheter placement were Th8/Th9 in 55 patients (36.7%) and Th7/Th8 in 41 patients (27.3%). Laparoscopy was performed in 129 patients (86.0%). Median NRS was five, and pneumonia occurred in 16 patients (10.7%). The epidural anesthesia group had a higher proportion of squamous cell carcinoma (88.5% vs. 73.0%, p = 0.024), lower lymphocyte counts (1680 vs. 2065, p = 0.020), diabetes (16.8% vs. 37.8%, p = 0.007), and hypertension (54.9% vs. 81.1%, p = 0.006), and circular stapler anastomosis (83.2% vs. 62.2%, p < 0.001). No significant differences were observed in the postoperative NRS, pneumonia, or length of postoperative hospital stay. Conclusions: There was no significant difference in the postoperative NRS and pneumonia between those with or without epidural analgesia in thoracoscopic esophagectomy.

Subarachnoid purulence is generally formed secondary to the rupture of brain abscesses. Early diagnosis of subarachnoid purulence unrelated to brain abscesses is challenging because of the lack of specific neurological or radiological findings. In this article, we report a case of localized subarachnoid purulence mimicking aneurysmal subarachnoid hemorrhage. A 74-year-old woman with diabetes and a history of rhinosinusitis presented with a sudden deterioration of the level of consciousness, tonic posture, and fever. A head computed tomography (CT) scan revealed a high-density area in the left Sylvian fissure. Subsequent CT angiography revealed an ipsilateral posterior communicating artery aneurysm, suggesting a diagnosis of aneurysmal subarachnoid hemorrhage. Craniotomy for surgical clipping of the presumed ruptured aneurysm revealed a subarachnoid purulence rather than a clot. Antimicrobial agents were administered, and endoscopic sinus surgery was performed to control the infection. Histopathological and microbiological examinations of the sphenoid sinusitis and intracranial specimen revealed Aspergillus, Prevotella intermedia, and Staphylococcus aureus. The functional outcome was poor because of delayed cerebral infarction associated with vascular invasion by the subarachnoid purulence.Localized subarachnoid purulence could be misdiagnosed as aneurysmal subarachnoid hemorrhage, particularly when an incidental aneurysm is detected. Laboratory and physical findings of systemic inflammation, as well as a history of rhinosinusitis, may help physicians add magnetic resonance imaging and lumbar puncture for early and definitive diagnosis of subarachnoid purulence.

Fusobacterium species, particularly Fusobacterium nucleatum, are anaerobic gram-negative bacteria found in the oral cavity and gastrointestinal tract. Infections caused by these organisms exhibit diverse clinical manifestations. Here we report a rare case of orbital abscess caused by Fusobacterium nucleatum, which was initially misdiagnosed as Tolosa-Hunt syndrome. The patient was controlled conservatively, and surgical intervention was withheld due to poor prognosis, diabetes, and logistical limitations. This case report highlights the need to consider infection even when imaging and laboratory tests are unremarkable, and to emphasize the importance of close follow-up of orbital abscesses due to its aggressive nature.

Abstract Background A fully automated echocardiographic analysis system utilizing artificial intelligence was provided. It enables to generate diagnostic reports based on guidelines through zero-click measurements. While the system is expected to shorten examination time, the accuracy of both measurements and diagnoses remains to be verified. In particular, left ventricular wall thickness and the four classifications of left ventricular hypertrophy (normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy) are prone to variation in real-world clinical practice. In this study, we aimed to investigate the diagnostic accuracy of the four classifications of left ventricular hypertrophy by automated measurement using this system. Methods A total of 100 patients with hypertension, observed during echocardiographic examination, were included to the study. The average measurements by a total of eight experts from four centers were used as the gold standard, and the same left ventricular long-axis cross-sectional moving images were compared for agreement between the fully automated measurements and the four classifications of left ventricular hypertrophy. For expert measurements of left ventricular wall thickness, after learning in a preliminary meeting using guidelines published by the Association for Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI), experts at each institution paired up and performed measurements engaging in discussion. For statistical analysis, we used the Student's t-test to compare continuous variables and the weighted kappa coefficients to assess diagnostic agreement. Results The fully automated echocardiographic analysis system was able to measure 89 of 100 cases. Automatic measurements of ventricular septal wall thickness and left ventricular posterior wall thickness were significantly higher than the average of four-center (10.7±2.2mm vs. 9.1±1.8mm, p&amp;lt; 0.05, and 10.1±2.3 mm vs. 8.9±1.7mm, p&amp;lt; 0.05, respectively). The weighted kappa coefficient for the four categories of left ventricular hypertrophy was 0.84. Analysis of the agreement rate by classification revealed that concentric hypertrophy showed the highest agreement rate (89.3%), followed by concentric remodeling (88.9%). In contrast, eccentric hypertrophy (40.5%) and normal (26.7%) showed lower concordance rates (Figure). Conclusions Although the fully automated echocardiographic analysis system tended to overestimate wall thickness, the agreement rate for left ventricular hypertrophy classification was high.

Oxytocin (OXT) is a neuropeptide known for its anti-inflammatory and neuroprotective properties; however, its role in post-stroke recovery remains poorly defined. In this study, we investigated whether intranasal OXT administration during the subacute phase of stroke improves neurological outcomes and modulates microglial responses. Male mice underwent permanent middle cerebral artery occlusion and received intranasal OXT (300ng/g) or saline on days 3 and 5 post-stroke. Neurological function was assessed using the modified neurological severity score; infarct volume was evaluated through hematoxylin-eosin (HE) staining, and survival rates were monitored until day 7. Immunofluorescence was used to assess microglial polarization in the peri-infarct region. OXT-treated mice showed significantly greater functional improvement and higher survival rates than saline-treated controls. Infarct volume was significantly reduced, and microglial polarization was altered by OXT, with a decrease in pro-inflammatory M1-type markers and an increase in anti-inflammatory M2-type markers. These findings demonstrate that OXT promotes neurological recovery through anti-inflammatory and neuroprotective mechanisms. Given its feasibility as a non-invasive delivery method, intranasal OXT may offer a promising therapeutic approach to enhance post-stroke neurorepair.