BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

Objective: Almost half of all patients with cancer experience dyspnea, which can have various causes. Although systemic corticosteroids are administered to relieve symptoms, their efficacy has not been established. This systematic review aims to determine the efficacy of systemic corticosteroids for dyspnea in patients with cancer. Methods: CENTRAL, MEDLINE, EMBASE, and Ichushi-Web databases were searched for articles published from their inception to September 23, 2019, on studies of systemic corticosteroid administration for dyspnea in patients with cancer. The primary outcome measure was dyspnea intensity, as assessed by patient-reported outcomes. Secondary outcome measures were quality of life, delirium, and severe adverse events. Results: Two RCTs were included in the meta-analysis. With regard to alleviating dyspnea, the systematic corticosteroid group was associated with significantly greater dyspnea relief than the placebo group (mean difference: −0.71 [95% CI: −1.4 to −0.03]). However, a meta-analysis of quality of life and delirium could not be performed due to insufficient data. Analysis of severe adverse events showed no significant difference in their incidence between the corticosteroid and control groups (relative rate: 0.96 [95% CI: 0.19-4.93]). Conclusions: Systemic corticosteroids may be effective in treating dyspnea in patients with cancer, particularly those with lung involvement. Limiting the conditions for which corticosteroids are approved is expected to promote their appropriate use and minimize their adverse effects. However, further investigation is needed to determine the appropriate dosage, and the conditions in which corticosteroids are effective.

Methods: This study included 46 patients who underwent spinal reconstruction surgery for thoracolumbar osteoporotic vertebral fractures and kyphosis and were followed up for 1 year postoperatively. DJK was defined as an advanced kyphosis angle >10° between the LIV and one lower vertebra. The patients were divided into groups with and without DJK. The risk factors of the two groups, such as patient background, surgery-related factors, radiographic parameters, and clinical outcomes, were analyzed. Results: The DJK and non-DJK groups included 14 and 32 patients, respectively, without significant differences in patient background. Those with instability in the distal adjacent LIV disc had a significantly higher risk of DJK occurrence (28.6% vs. 3.2%, p=0.027). DJK occurrence significantly increased in those with the sagittal stable vertebra not included in the fixation range (57.1% vs. 18.8%, p=0.020). Other preoperative radiographic parameters were not significantly different. Instability in the distal adjacent LIV disc (adjusted odds ratio, 14.50; p=0.029) and the exclusion of the sagittal stable vertebra from the fixation range (adjusted odds ratio, 5.29; p=0.020) were significant risk factors for DJK occurrence. Conclusions Regarding spinal reconstruction surgery in patients with osteoporotic vertebral fractures, instability in the distal adjacent LIV disc and the exclusion of the sagittal stable vertebra from the fixation range were risk factors for DJK occurrence in the short term.

Objective: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian carcinoma with poor prognosis. However, no effective biomarkers have been established for predicting unfavorable events, including recurrence and poor prognoses. Serum microRNAs (miRNAs) have been increasingly reported to be useful in predicting a patient’s condition and have been recognized as a potentially less-invasive source for liquid biopsy in cancer. Therefore, this study aimed to evaluate serum miRNA profiles from patients with OCCC and to establish biomarker for predicting the prognoses. Methods: The GSE106817, which included preoperative serum miRNA profiles of patients with ovarian tumors, was used, and clinical information was investigated. In all, 66 patients with OCCC were included, excluding those with other histological subtypes or insufficient prognostic information. Moreover, miRNA profiles of OCCC tissues were also examined. Results: The median follow-up period was 64.3 (8.0–153.3) months. Based on multivariable Cox regression analyses and the expression of miRNAs in OCCC tissues, miR-150-3p, miR-3195, and miR-7704 were selected as miRNA candidates associated with both progression-free survival (PFS) and overall survival (OS). Then, the prognostic index was calculated based on expression values of 3 serum miRNAs. Kaplan-Meier survival analysis indicated that the prognostic index was significantly predictive of PFS and OS (p=0.004 and p=0.012, respectively). Conclusion Preoperative serum miRNA profiles of miR-150-3p, miR-3195, and miR-7704 can be used to potentially predict the prognosis of patients with OCCC.

Background/Aims: Golimumab (GLM) is an anti-tumor necrosis factor-α drug approved for treating moderate-to-severe active ulcerative colitis (UC). A 52-week post-marketing surveillance (PMS) was initiated to evaluate its safety and effectiveness in patients with UC in Japan. We present an interim report of the ongoing PMS. Methods: Patients received 200 mg of subcutaneous GLM at week 0, 100 mg at week 2, and 100 mg 4 weekly thereafter. The safety analysis set included 392 patients with UC, and the effectiveness analysis set 387 patients. Safety and effectiveness were assessed at week 6. Results: Adverse drug reactions (ADRs) were reported in 8.2% (32/392) and serious ADRs in 4.6% (18/392). The most frequent ADRs were infection and infestation (3.3%), with herpes zoster being the most common. ADRs were significantly higher in patients with concomitant corticosteroid use (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.40–9.68). No significant difference in ADR incidence was observed between patients aged ≥65 and <65 years (OR, 1.23; 95% CI, 0.35–3.47). Six-week effectiveness of GLM was confirmed by a decrease in the partial Mayo score (–2.3; 95% CI, –2.6 to –2.1) and C-reactive protein levels (–0.64; 95% CI, –0.92 to –0.36), including in the biologics-experienced population. Conclusions The safety and effectiveness of GLM at week 6 in a real-world setting were demonstrated in patients with UC in Japan. ADR patterns were consistent with previous reports with no new safety signals. Concomitant corticosteroid use may be associated with increased ADR incidence. The final results of the ongoing PMS are necessary for further evaluation.

The purpose of this study is to clarify factors related to the effect of daikenchuto on constipation during pregnancy. The subjects were 21 patients who had constipation during pregnancy and received 15 g/day of daikenchuto. Based on the constipation score that was created independently, the score values before administration, 2 weeks and 4 weeks after administration were retrospectively investigated. Furthermore, from the outcome of the oral status at 4 weeks, we divided the patients into 2 groups (12 in the improvement group and 11 in the non-improvement group), and attempted to extract factors that were considered to be related to efficacy. The total constipation score decreased significantly before and after administration of daikenchuto, and the concomitant symptoms of constipation scores were low, especially such as abdominal distension and abdominal pain. A comparison of the backgrounds of the improved group and the non-improved group revealed that the proportion of the patients with a history of surgery (laparotomy or laparoscopic surgery) was significantly higher in the improvement group. In addition, there were no particular problems with the pregnancy and delivery course of the 23 patients. Daikenchuto was considered to be highly effective against constipation during pregnancy, especially in pregnant women with a history of surgery.

Methods: We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. Results: In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. Conclusions FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.

Background/Aims: The aim of this study was to evaluate the safety of sedation with propofol as an alternative to benzodiazepine drugs in outpatient endoscopy. Methods: In this prospective study, examinees who underwent outpatient endoscopy under propofol sedation and submitted a nextday questionnaire with providing informed consent were evaluated. Periprocedural acute responses, late adverse events within 24 hours, and examinee satisfaction were evaluated. Results: Among the 4,122 patients who received propofol in the 17,978 outpatient-based endoscopic examinations performed between November 2016 and March 2018, 2,305 eligible examinees (esophagogastroduodenoscopy for 1,340, endoscopic ultrasonography for 945, and total colonoscopy for 20) were enrolled, and their responses to a questionnaire were analyzed. The mean propofol dose was 69.6±24.4 mg (range, 20–200 mg). Diazepam, midazolam, and/or pentazocine in combination with propofol was administered to 146 examinees. Mild oxygen desaturation was observed in 59 examinees (2.6%); and mild bradycardia, in 2 (0.09%). Other severe reactions or late events did not occur. After eliminating 181 invalid responses, 97.7% (2,065/2,124) of the patients desired propofol sedation in future examinations. Conclusions Propofol sedation was found to be safe—without severe adverse events or accidents—for outpatient endoscopy on the basis of the patients’ next-day self-evaluation. Given the high satisfaction level, propofol sedation might be an ideal tool for painless endoscopic screening.

Methods: We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. Results: In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. Conclusions FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.