The aim of this study was to clarify the nature of psychological conflict among men aged 80 years or older who were living alone in eight depopulated municipalities designated by Japan's Ministry of Internal Affairs and Communications. Semi-structured interviews were conducted with 34 elderly men who were living alone. Text-mining analysis revealed that elderly men living alone in depopulated villages were feeling lonely because they [did not have anyone to talk to] but did not want to leave their homes. They were aware of [progressive decline in physical functions] after the age of 80 and thought that [it would be the end if no longer being able to walk]. Because they needed to drive a car in order to continue living their lives, they were [conflicted about continuing to drive] and [anxious that they would not be able to go shopping] if they were to stop driving. The elderly men living in depopulated villages had developed human relationships and attachments to their hometowns, and they wanted to continue living in the homes they were born and raised in until the end of their lives. At the same time, they were struggling with conflicts related to loneliness caused by the weakening of human relationships, feelings of self-deficiency due to physical decline, and a sense of crisis stemming from the decline of the community. On the other hand, one factor supporting them was their motivation to protect the community. These findings suggest the need for a community care system that helps older people feel a sense of solidarity with, and a sense of contribution to, the community.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. Methods: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. Results: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4). Conclusions Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.

The human fetal sacroiliac joint (SIJ) is characterized by unequal development of the paired bones and delayed cavitation. Thus, during the long in utero period, the bony ilium becomes adjacent to the cartilaginous sacrum. This mor phology may be analogous to that of the temporomandibular joint (TMJ). We examined horizontal histological sections of 24 fetuses at 10–30 weeks and compared the timing and sequences of joint cartilage development, cavitation, and ossification of the ilium. We also examined histological sections of the TMJ and humeroradial joint, because these also contain a disk or disk-like structure. In the ilium, endochondral ossification started in the anterior side of the SIJ, extended posteriorly and reached the joint at 12 weeks GA, and then extended over the joint at 15 weeks GA. Likewise, the joint cartilage appeared at the anterior end of the future SIJ at 12 weeks GA, and extended along the bony ilium posteriorly to cover the entire SIJ at 26 weeks GA. The cavitation started at 15 weeks GA. Therefore, joint cartilage development seemed to follow the ossification of the ilium by extending along the SIJ, and cavitation then occurred. This sequence “ossification, followed by joint cartilage formation, and then cavitation” did not occur in the TMJ or humeroradial joint. The TMJ had a periosteum-like membrane that covered the joint surface, but the humeroradial joint did not. After muscle contraction starts, it is likely that the mechanical stress from the bony ilium induces development of joint cartilage.

BRCA2 Protein/genetics* ; Germ Cells ; Humans ; Male ; Muscular Atrophy ; Mutation ; Prostate ; Prostatic Neoplasms/genetics*

Objective: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. Methods: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. Results: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Conclusion The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

Introduction: The diagnosis of cancer-related neuropathic pain is often difficult for non-pain medicine specialists. We examined whether a Japanese version of a neuropathic pain screening questionnaire (Japan-Q), which was developed for chronic pain, is appropriate for screening cancer-related neuropathic pain. Methods: Our palliative care team screened 104 patients from May 2014 to December 2015 and compared total points of the Japan-Q with diagnosis of the type of cancer pain by specialized pain clinicians. Validity was evaluated using a receiver operating characteristic (ROC) curve. Results: The area under the ROC curve in terms of the total score, sensitivity, and specificity for the Japan Q was 0.82, which indicated a moderate level of diagnostic accuracy. A cut-off value of 3 points was shown to be best (sensitivity: 79%, specificity: 82%). When a cut-off value of 9 points was used as the diagnostic criterion for neuropathic pain, there was greatly reduced sensitivity (sensitivity: 40%, specificity: 97%). Conclusion: Although the Japan-Q shows moderate diagnostic accuracy related to cancer pain, the cut-off value for this tool is lower than that for chronic pain. Cancer-related neuropathic pain should be suspected with a total score of 3 or more in the Japan-Q.

BACKGROUND/AIMS: Although the risk of bleeding after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is low, the safety of EUS-FNA in patients prescribed antithrom-botic agents is unclear. Therefore, this study evaluated the incidence of bleeding after EUS-FNA in those patients. METHODS: Between September 2012 and September 2015, patients who were prescribed antithrombotic agents underwent EUS-FNA at 13 institutions in Japan were prospectively enrolled in the study. The antithrombotic agents were managed according to the guidelines of the Japanese Gastrointestinal Endoscopy Society. The rate of bleeding events, thromboembolic events and other complications within 2 weeks after EUS-FNA were analyzed. RESULTS: Of the 2,629 patients who underwent EUS-FNA during the study period, 85 (62 males; median age, 74 years) patients were included in this stduy. Two patients (2.4%; 95% confidence interval [CI], 0.6% to 8.3%) experienced bleeding events. One patient required surgical intervention for hemothorax 5 hours after EUS-FNA, and the other experienced melena 8 days after EUS-FNA and required red blood cell transfusions. No thromboembolic events occurred (0%; 95% CI, 0.0% to 4.4%). Three patients (3.5%; 95% CI, 1.2% to 10.0%) experienced peri-puncture abscess formation. CONCLUSIONS: The rate of bleeding after EUS-FNA in patients prescribed antithrombotic agents might be considerable.
Abscess ; Asian Continental Ancestry Group ; Endoscopic Ultrasound-Guided Fine Needle Aspiration* ; Endoscopy, Gastrointestinal ; Erythrocyte Transfusion ; Fibrinolytic Agents* ; Hemorrhage* ; Hemothorax ; Humans ; Incidence ; Japan ; Male ; Melena ; Prospective Studies*

Objective：The objective of this study was to apply Least Absolute Shrinkage and Selection Operator （LASSO）logistic regression to detection of adverse drug reaction （ADR） signals using an electronic health records database as a comprehensive and quantitative method to supplement the current pharmacovigilance activities in Japan.

Design：case-control study

Methods：We analyzed data from 40767 inpatients using a single-institution hospital database and identified two ADRs, suspected pancreatitis and thrombocytopenia, using abnormal laboratory test results. LASSO logistic regression analysis was applied to detect ADR signals with adjustment for age, sex, comorbidities and medical procedures. The positive predictive value （PPV） was calculated using reference standard of known drug-ADR associations based on drug product labels.

Results：The number of case group was 6735 for suspected pancreatitis and 11561 for thrombocytopenia. The number of ADR signals detected using LASSO logistic regression was 27 for suspected pancreatitis and 40 for thrombocytopenia. The calculated PPV was 3.7% for suspected pancreatitis and 55.0% for thrombocytopenia.

Conclusion：LASSO logistic regression analysis efficiently detects ADR signals by adjusting for confounding factors such as comorbidities and medical procedures. The false positive signals may contain unknown signals and further signal assessment will be needed.

Introduction: We report a very rare case of paraneoplastic chorea due to lung cancer that was ameliorated by administering tetrabenazine, the only agent used for treating the chorea of Huntington disease. Case: A 92-year-old woman was diagnosed with lung cancer but only followed up, based on advanced age and her own wishes. Given the absence of treatments such as chemotherapy, the lung cancer was not histologically diagnosed. During follow-up, involuntary movements appeared and paraneoplastic chorea was diagnosed. Therefore, she could not live alone and was admitted to a nursing home. Triple combination therapy with valproic acid, tiapride hydrochloride and risperidone was started, and showed efficacy for her symptoms. The symptoms showed amelioration but persisted in the upper extremities, face and neck. A neurologist suggested to her family that tetrabenazine, the only medication used for Huntington’s chorea, might be effective. After admission to our hospital, her family requested tetrabenazine. As both she and her family were suffering mental distress because “she was trapped in a body that moved regardless of her will”, we initiated tetrabenazine at a dose of 12.5 mg/day. After starting tetrabenazine, chorea of the upper extremities, face and neck almost disappeared. Moreover, her speech became clear and she spoke normally with her family. Discussion: Tetrabenazine is a drug receiving insurance reimbursement only for Huntington’s chorea, but was effective in this case. In our view, this treatment palliated the patient’s physical distress and the mental distress that she and her family were experiencing due to her paraneoplastic chorea.

Objective：The objective of this study was to apply Least Absolute Shrinkage and Selection Operator （LASSO）logistic regression to detection of adverse drug reaction （ADR） signals using an electronic health records database as a comprehensive and quantitative method to supplement the current pharmacovigilance activities in Japan.Design：case-control studyMethods：We analyzed data from 40767 inpatients using a single-institution hospital database and identified two ADRs, suspected pancreatitis and thrombocytopenia, using abnormal laboratory test results. LASSO logistic regression analysis was applied to detect ADR signals with adjustment for age, sex, comorbidities and medical procedures. The positive predictive value （PPV） was calculated using reference standard of known drug-ADR associations based on drug product labels.Results：The number of case group was 6735 for suspected pancreatitis and 11561 for thrombocytopenia. The number of ADR signals detected using LASSO logistic regression was 27 for suspected pancreatitis and 40 for thrombocytopenia. The calculated PPV was 3.7% for suspected pancreatitis and 55.0% for thrombocytopenia.Conclusion：LASSO logistic regression analysis efficiently detects ADR signals by adjusting for confounding factors such as comorbidities and medical procedures. The false positive signals may contain unknown signals and further signal assessment will be needed.