Kanazawa Hospital

Porphyrias are rare metabolic disorders caused by decreased or increased activity of one of the nine enzymes involved in the heme biosynthetic pathway, resulting in the accumulation of porphyrins or their precursors. Although nine subtypes are currently recognized, substantial overlap in clinical manifestations often makes diagnosis challenging. This article presents the English version of the first national clinical practice guidelines for porphyrias in Japan, originally published in 2025 by the Japanese Dermatological Association. The guidelines were developed by the Clinical Practice Guideline Committee, established as part of the Research Project on Intractable Diseases of the Ministry of Health, Labour and Welfare of Japan. Diagnostic and severity assessment criteria were based on those proposed by the Ministry research group. Clinical questions (CQs) were formulated, and recommendations were developed according to the principles of evidence-based medicine, incorporating both domestic and international evidence. The guidelines provide diagnostic criteria, severity classification, and evidence-based recommendations for the management of porphyrias. Although causative genes have been identified, the pathophysiology remains incompletely understood, and no curative therapy is currently available, and liver transplantation may be required in severe cases with liver failure. These guidelines aim to provide practical guidance for clinicians managing porphyrias in Japan. Future revisions will be necessary in response to advances in diagnostic technologies and therapeutic strategies.

This study aims to examine the current practice patterns of Japanese urologists in treating male anterior urethral strictures and to compare these results with international trends. A 16-item questionnaire, adapted from surveys conducted in other countries, was distributed to members of the Japanese Urological Association (JUA) in 2024. Statistical analyses, including Pearson's chi-square test and logistic regression, were performed to identify factors influencing treatment preferences. We emailed 9898 JUA members, and 1028 (10.4%) responded. 835 (81.2%) handled five or fewer urethral stricture cases annually. While 968 (94.2%) had experience with urethral dilatation, 937 (91.1%) with direct vision internal urethrotomy (DVIU), only 308 (30.0%) had experience with excision and primary anastomosis, and 102 (9.9%) with any oral mucosal graft urethroplasty. For the two hypothetical clinical cases, referring to specialists was selected in 707 (68.8%) and 618 (60.1%), respectively, whereas urethroplasty was chosen in 133 (12.9%) and 243 (23.6%), respectively. Seven hundred seventy-four (75.3%) felt the literature supported going straight to definitive urethroplasty if necessary, and this was significantly associated with being under 50 years of age, holding instructor status, and limiting the indication for DVIU to strictures ≤ 1 cm. Japanese urologists exhibit limited urethroplasty experience and widely utilize transurethral treatments. The majority of members prefer to refer to a specialist, indicating that, in addition to the difficulty of urethroplasty, making indication decisions is also challenging. It is hoped that evidence-based medical practice will become more widespread.

Medial opening wedge high tibial osteotomy (MOWHTO) is an effective surgical procedure for joint preservation in active patients with medial knee osteoarthritis (KOA). However, older patients and those with prolonged preoperative sports cessation often struggle to resume high-impact activities, such as running, after MOWHTO. Remote rehabilitation tools may help overcome these challenges. We report the case of an older woman with prolonged cessation of sports activity who resumed sports activity after MOWHTO with the help of the mymobility® smartphone application. A 71-year-old woman with Kellgren-Lawrence grade 3 medial KOA and -5° varus alignment underwent MOWHTO. She discontinued daily 7 km runs for two years owing to knee pain. The preoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were 53 for Symptoms, 50 for Pain, 61 for Activities of Daily Living, 25 for Sport and Recreation Function, and 6.25 for Quality of Life, and the Oxford Knee Score (OKS) was 31. Bone union was achieved on postoperative day (POD) 90. However, she maintained a low step count (approximately 2000 steps/day) and was unable to run owing to anxiety. We used mymobility® to provide chat-based guidance, step-count goals, and video assessments of jogging and running form. Activity progressively increased, and she achieved jogging ability on POD 150 and pain-free running ability on POD 180. Her Visual Analog Scale score improved to 0 mm, KOOS and OKS scores improved substantially, and step count increased to approximately 8000 steps/day. This case indicates that mymobility® can facilitate safe and timely return to sports after MOWHTO by improving motivation, providing remote supervision, and enabling individualized activity progression. mymobility® may be particularly effective for older patients or those who cannot access specialized postoperative rehabilitation services.

ABSTRACTIn this study, we identified prognostic biomarkers that predict treatment outcome in patients receiving fertility‐preserving high‐dose medroxyprogesterone acetate (MPA) therapy through comprehensive multigene panel testing. A total of 38 patients (20 atypical endometrial hyperplasia and 18 stage IA G1 without myometrial invasion) who received first‐line MPA therapy were enrolled. Genomic DNA was extracted from formalin‐fixed paraffin‐embedded samples, and PleSSision‐Rapid multigene panel testing was performed. Of the 38 patients, 31 (82%) achieved complete response (CR), 2 (5%) had stable disease (SD), and 5 (13%) had progressive disease (PD) following initial treatment. The median duration to achieve tumor disappearance was 7 months (range: 4–14 months). Following initial treatment, 25 of 32 patients (78%) experienced recurrence, with a median recurrence‐free survival (RFS) of 21 months (range: 2–84 months). The most frequently observed actionable gene mutations were PTEN (68.4%), CTNNB1 (55.2%), and PIK3CA (33.3%). Patients harboring PTEN mutations in EMG1 required a significantly longer duration to achieve tumor disappearance (p = 0.011). In addition, the presence of PIK3CA mutations in AEH was significantly associated with shorter RFS (p = 0.048). Molecular classification identified 34 patients (89%) with no specific molecular profile (NSMP), 1 patient (3%) with POLE mutation, and 3 patients (8%) with deficient mismatch repair (d‐MMR). Most patients undergoing MPA therapy were classified as having NSMP. Genetic alterations, specifically mutations in PTEN and PIK3CA, were significantly associated with treatment outcomes, highlighting their potential as prognostic biomarkers.

[This corrects the article DOI: 10.7759/cureus.84130.].

BackgroundSeizures are a common consequence of acute hemorrhagic stroke, which has a high morbidity and fatality rate. It is yet unknown how they relate to age, the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and discharge status.MethodsWe conducted a cross-sectional study of 75 patients (aged 16-92 years) with acute hemorrhagic stroke admitted to the Neuropsychiatry Department of Qena University Hospitals, a tertiary care center serving a large catchment area in Upper Egypt. Data were collected over six months, from September 2024 to February 2025. Neurological impairment was assessed using the NIHSS, and functional outcome was measured using the mRS at admission and discharge. Statistical comparisons included paired t-tests and Wilcoxon signed-rank tests. Associations between seizures, age, stroke severity, and outcomes were also analyzed.ResultsSeizures were not correlated with age. During hospitalization, a noteworthy mean improvement in NIHSS (+0.97; t = 10.70 and p < 0.0001; W = 21.50 and p < 0.0001) was noted, suggesting neurological recovery. On the other hand, mRS remained at a median 3 (t = -0.51 and p = 0.6113; W = 275 and p = 0.9173), indicating no discernible change. There was no discernible change in NIHSS or mRS among patients who were released on demand (n = 10). Ten out of the 12 in-hospital fatalities had seizures, and the majority had moderate-to-severe strokes (NIHSS ≥9; mRS ≥3). Patients with very severe strokes (NIHSS 16-17; mRS = 5) and no recovery experienced two non-seizure fatalities. Admission NIHSS (1-17) and mRS (1-5) showed a broad variety of stroke presentations and recovery trajectories.ConclusionThe baseline of stroke severity was the best indicator of a bad prognosis in acute hemorrhagic stroke, and seizure incidence was not age-dependent. Significant neurological recovery was recorded by NIHSS, but short-term functional improvement was not reflected by mRS. These results indicate that seizures are more common in fatal cases but secondary to the total load of strokes, underscoring the prognostic significance of baseline severity.

BackgroundThe real-world efficacy of the P2X3 antagonist gefapixant, a new class of antitussive for refractory chronic cough, is not yet fully understood. This study aimed to evaluate the real-world usage and response to gefapixant in patients with refractory chronic cough.MethodsThis multicentre retrospective study involved patients with refractory chronic cough who visited cough clinics and were prescribed gefapixant. Data collected included baseline demographics, cough characteristics, response to gefapixant, degree of taste disturbance (both assessed by cough specialists), and the course of cough after discontinuation, if applicable.Results272 cases were analysed. The population was predominantly middle-aged females, with most patients having asthmatic cough as a comorbidity, dry cough, and predominantly daytime cough. Half of the patients reported a response rate of ≥5 on a 0–10 scale, with 25% reporting a response rate of ≥8. Among responders (response rate ≥5), improvement was largely seen within 2 weeks. The median treatment duration with gefapixant was 32 days (interquartile range 14–175 days), with longer treatment periods observed in responders. Responders typically had more severe pre-treatment cough, dry cough, asthmatic cough as a comorbidity and specific laryngeal sensations. In patients who discontinued gefapixant, sustained improvement was observed in responders. Taste disturbance was not associated with response to gefapixant and was less frequent in patients with cough triggers such as smoke, dry air, or scents, than in those without these triggers.ConclusionsGefapixant demonstrated a rapid and effective antitussive effect in this multicentre, real-world study.

Gambling disorder (GD) is often comorbid with other psychiatric disorders. Previous studies have reported that psychiatric comorbidity increases both treatment dropout and relapse among patients with GD. However, little is known about the effects of comorbidity among outpatients with GD either during or after treatment. This study examined this issue in a clinical setting. 60 outpatients with GD (men/women, 58/2; average age, 37.9 years) participated in assessments of the course of multidimensional treatment outcomes (i.e., gambling-related variables, social impairment, and depressive symptoms) at three time points (baseline, 3 months, and 12 months). We examined treatment outcomes in GD patients with and without comorbidity. A total of 58.3% of the patients had comorbidities (major depressive disorder, 26.7%; behavioral addiction, 21.7%; anxiety disorder, 15.0%, etc.), while the dropout rates across the study period were 13.3% at 3 months and 35.0% at 12 months. Statistical analyses indicated that the South Oaks Gambling Screen score and the Sheehan Disability Scale score were significantly reduced at follow-up compared to baseline in both comorbid and non-comorbid outpatients. There was a significant difference for being still in treatment, where the proportion of individuals with comorbid disorders was significantly higher than those without comorbidities at the 12-month compared to the 3-month follow-up. The proportion of all outpatients who remained abstinent from gambling at 12 months was significantly lower compared to baseline and at 3 months. Being still in treatment for comorbid psychiatric problems may affect the course and outcome of GD treatment.