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*

Purpose: The albumin-to-globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC. Methods: The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52–14.18 and adjusted OR, 4.97; 95% CI, 2.14–12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56–11.51 and adjusted OR, 5.22; 95% CI, 1.97–14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06–21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found. Conclusion Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.

Objective: Bevacizumab maintenance therapy following platinum-based combination chemotherapy for metastatic, recurrent, or persistent cervical cancer is not recommended as standard therapy. This pilot study aimed to evaluate the efficacy and safety of bevacizumab maintenance therapy and the contribution of the platinum-free interval to the efficacy of subsequent chemotherapy for advanced cervical cancer. Methods: We retrospectively identified 115 patients with metastatic, recurrent, or persistent cervical cancer treated with platinum-paclitaxel chemotherapy plus bevacizumab at 7 institutions between 2015 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients who received bevacizumab maintenance therapy and those who did not. We also analyzed the adverse events associated with bevacizumab and survival time from the start of subsequent chemotherapy in both groups. Results: Following platinum-paclitaxel plus bevacizumab chemotherapy, 34 patients received bevacizumab maintenance therapy and 81 patients did not. Of the 115 patients, 56 received chemotherapy for subsequent relapse. Although bevacizumab maintenance therapy prolonged PFS (median of 16.0 months vs. 9.0 months, p=0.041), significant differences were not observed in OS (p=0.374). Furthermore, bevacizumab maintenance therapy did not prolong OS and PFS after the start of subsequent chemotherapy (p=0.663 and p=0.136, respectively). Bevacizumab maintenance therapy significantly increased hypertension (p=0.035) and proteinuria (p=0.005) but did not cause complications leading to death. Conclusion Bevacizumab single-maintenance therapy for advanced cervical cancer can be considered in selected cases, such as those with acceptable bevacizumab-related side effects. The outcomes of our study will likely contribute to decision-making regarding practical treatment strategies.

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.

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.

Objective: In this study we sought to investigate the clinical factors that affect postprogression survival (PPS) in patients with recurrent or persistent clear cell carcinoma (CCC).We utilized the JGOG3017/Gynecological Cancer InterGroup data to compare paclitaxel plus carboplatin (TC) and irinotecan plus cisplatin (CPT-P) in the treatment of stages I to IV CCC. Methods: We enrolled 166 patients with recurrent or persistent CCC and assessed the impact of variables, including platinum sensitivity, treatment arm, crossover chemotherapy, primary stage, residual tumor at primary surgery, performance status, ethnicity, and tumor reduction surgery at recurrence on the median of PPS in patients with recurrent or persistent CCC. Results: A total of 77 patients received TC, and 89 patients received CPT-P. The median PPS for patients with platinum-resistant disease was 10.9 months, compared with 18.8 months for patients with platinum-sensitive disease (hazard ratio [HR]=1.88; 95% confidence interval [CI]=1.30–2.72; log-rank p<0.001). In the multivariate analysis, the platinum sensitivity (resistant vs. sensitivity; HR=1.60; p=0.027) and primary stage (p=0.009) were identified as independent predictors of prognosis factors for PPS in recurrent or persistent CCC. Conclusions Our findings revealed that platinum sensitivity and primary stage are clinical factors that significantly affect PPS in patients with recurrent or persistent CCC as wellas other histologic subtypes of ovarian cancer. PPS in patients with recurrent CCC should establish the basis for future clinical trials in this population.

STUDY DESIGN: Retrospective case series. PURPOSE: To examine the efficacy of TachoSil for vessel injury in 6 patients who underwent anterior lumbar fusion surgery (ALF). OVERVIEW OF LITERATURE: ALF for the lumbar spine has a high rate of success, although intraoperative concerns and iatrogenic complications are known, and injury of a major vessel is sometimes a complication. The efficacy of TachoSil, a fibrin-based hemostat, has been reported for several types of surgery; however, use of TachoSil for ALF surgery has not been described. Here, we report on the efficacy of TachoSil in 6 patients, who underwent ALF after vascular surgeons having difficulty in repairing vessels. METHODS: Two man and 4 women with average age of 50.8±10.9 (mean±standard deviation) were diagnosed with a vertebral tumor (2 patients), L4 degenerative spondylolisthesis (2 patients), and L5 spondylolytic spondylolisthesis (2 patients) and underwent ALF. The blood vessels injured included the common iliac vein in 2 patients and a branch of a segmental artery from the aorta in 4 patients. We consulted a vascular surgeon to suture or repair the vessels during surgery, and although the vascular surgeon attempted to address the injuries, suturing or repair was not possible in these cases. For this reason, we used TachoSil to repair the injury in the vessels walls or to stop the bleeding. RESULTS: Time to pressure hemostasis using TachoSil was 34±12 minutes, and total blood loss was 1,488±1,711 mL. Nevertheless, all vessel injuries were controlled by the use of TachoSil. CONCLUSIONS: We recommend the use of TachoSil for vessel injuries that vascular surgeons cannot suture or repair during ALF surgery.
Aorta ; Arteries ; Blood Vessels ; Female ; Hemorrhage ; Hemostasis ; Humans ; Iliac Vein ; Retrospective Studies ; Spine* ; Spondylolisthesis ; Surgeons ; Sutures

PURPOSE: To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS. MATERIALS AND METHODS: The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment. RESULTS: The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122). CONCLUSION: The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.
Adult ; Aged ; Aged, 80 and over ; Decompression, Surgical ; Female ; Humans ; Leg/*pathology ; Low Back Pain/epidemiology/etiology ; Male ; Middle Aged ; Pain/*epidemiology/*etiology ; Prospective Studies ; Questionnaires ; Spinal Stenosis/*complications/*physiopathology/surgery

STUDY DESIGN: A retrospective study. PURPOSE: To compare clinical and radiological outcomes between bilateral C2 pedicle screwing (C2PS) and unilateral C2PS, combined with contralateral C2 laminar screwing (LS), for posterior atlantoaxial fixation. OVERVIEW OF LITERATURE: Posterior fixation with C1 lateral mass screwing (C1LMS) and C2PS (C1LMS-C2PS method) is an accepted procedure for rigid atlantoaxial stabilization. However, conventional bilateral C2PS is not always allowed in this method due to anatomical variations of C2 pedicles and/or asymmetry of the vertebral artery. Although unilateral C2PS plus contralateral LS (C2PS+LS) is an alternative in such cases, the efficacy of this procedure has not been evaluated in controlled studies (i.e., with bilateral C2PS as a control). METHODS: Clinical and radiological records of patients who underwent the C1LMS-C2PS method, using unilateral C2PS+LS (n=9), and those treated using conventional bilateral C2PS (n=10) were compared, with a minimum two years follow-up. RESULTS: Postoperative complications related to the unilateral C2PS+LS technique included one case of spontaneous spinous process fracture of C2. A C1 anterior arch fracture occurred after a fall in one patient, who underwent bilateral C2PS and C1 laminectomy. No significant differences were seen between the groups in reduction of neck pain after surgery or improvement of neurological status, as evaluated using the Japanese Orthopaedic Association score. A delayed union occurred in one patient each of the groups, with the final fusion rate being 100% in both groups. CONCLUSIONS: Clinical and radiological outcomes of unilateral C2PS+LS were comparable with those of the bilateral C2PS fixation technique for the C1LMS-C2PS method.
Asian Continental Ancestry Group ; Follow-Up Studies ; Humans ; Laminectomy ; Neck Pain ; Postoperative Complications ; Retrospective Studies ; Vertebral Artery

PURPOSE: The pathological mechanism of lumbar spinal stenosis is reduced blood flow in nerve roots and degeneration of nerve roots. Exercise and prostaglandin E1 is used for patients with peripheral arterial disease to increase capillary flow around the main artery and improve symptoms; however, the ankle-brachial index (ABI), an estimation of blood flow in the main artery in the leg, does not change after treatment. Lumbar spinal nerve roots contain somatosensory, somatomotor, and unmyelinated autonomic nerves. Improved blood flow by medication with prostaglandin E1 and decompression surgery in these spinal nerve roots may improve the function of nerve fibers innervating muscle, capillary, and main vessels in the lower leg, resulting in an increased ABI. The purpose of the study was to examine whether these treatments can improve ABI. MATERIALS AND METHODS: One hundred and seven patients who received conservative treatment such as exercise and medication (n=56) or surgical treatment (n=51) were included. Low back pain and leg pain scores, walking distance, and ABI were measured before treatment and after 3 months of conservative treatment alone or surgical treatment followed by conservative treatment. RESULTS: Low back pain, leg pain, and walking distance significantly improved after both treatments (p<0.05). ABI significantly increased in each group (p<0.05). CONCLUSION: This is the first investigation of changes in ABI after treatment in patients with lumbar spinal stenosis. Improvement of the spinal nerve roots by medication and decompression surgery may improve the supply of blood flow to the lower leg in patients with lumbar spinal stenosis.
Adult ; Aged ; Aged, 80 and over ; Alprostadil/therapeutic use ; *Ankle Brachial Index ; Decompression, Surgical/methods ; Female ; Humans ; Low Back Pain/drug therapy/physiopathology/surgery/*therapy ; Lumbar Vertebrae/physiopathology/*surgery ; Male ; Middle Aged ; Pain/surgery ; Spinal Nerve Roots/physiopathology ; Spinal Stenosis/physiopathology/*surgery/*therapy ; Treatment Outcome