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*

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Methods: This retrospective study included 35 patients (mean age, 72.8±8.0 years; male, 10; female, 25) who underwent lumbosacral fixation using SAI screws with at least 2 years of follow-up. SAI screw loosening and L5–S bony fusion were assessed using computed tomography. The period for which the screws appeared loose and the risk factors for SAI screw loosening were investigated 2 years after surgery. Results: A total of 70 SAI screws and 70 S1 pedicle screws were inserted. Loosening was observed 0.5, 1, and 2 years after surgery in 17 (24.3%), 35 (50.0%), and 35 (50.0%) SAI screws, respectively. Bony fusion rate at L5–S was significantly lower in patients with SAI screw loosening than in those without screw loosening (65.0% vs. 93.3%, p =0.048). The score for SAI screw contact with the iliac cortical bone and the bony fusion rate at L5–S were significantly lower in the loosening group than in the non-loosening group (1.8±0.5 vs. 2.2±0.3, p <0.001, respectively). Postoperative pelvic incidence–lumbar lordosis was significantly higher in the loosening group than in the non-loosening group (7.9°±15.4° vs. 0.5°±8.7°, p =0.02, respectively). Conclusions SAI screw loosening is closely correlated with pseudoarthrosis at L5–S. Appropriate screw insertion and optimal lumbar lordosis restoration are important to prevent postoperative complications related to SAI screws.

Methods: We retrospectively investigated 52 cases involving lumbar interbody fusions for restenosis with spondylolisthesis after lumbar decompressions; these cases consisted of 15 patients who underwent indirect decompression with LLIF and posterior fixation and 37 patients who underwent the same procedure with PLIF. We compared Japanese Orthopaedic Association (JOA) scores and perioperative complications between groups. The cross-sectional areas of the thecal sac on magnetic resonance imaging were measured before, immediately after, and 2 years after surgery. We conducted statistical analyses using unpaired t -test and Fisher’s exact tests, and a p -value <0.05 was considered statistically significant. Results: The operative time was significantly shorter in the LLIF group than in the PLIF group (115.3±33.6 min vs. 186.2±34.2 min, respectively; p <0.001). In addition, the intraoperative blood loss was significantly lower in the LLIF group than in the PLIF group (58.2±32.7 mL vs. 303.2±140.1 mL, respectively; p <0.001). We found two cases of transient lateral thigh weakness (13.3%) in the LLIF group and five cases of incidental durotomy, one case of deep infection, and one case of neurological deterioration in the PLIF group—resulting in a higher complication incidence (18.9%), although it did not reach (p =0.63). The JOA scores improved significantly in both groups. Conclusions Indirect decompression using LLIF provided acceptable clinical and radiographical outcomes in patients with restenosis with spondylolisthesis after lumbar decompression; no revision-surgery-specific complications were found. Our results suggest that LLIF is a safe and minimally invasive procedure for revision surgery.

STUDY DESIGN: Retrospective case–control study. PURPOSE: To compare surgical invasiveness and radiological outcomes between posterior lumbar interbody fusion (PLIF) and lateral lumbar interbody fusion (LLIF) for degenerative lumbar kyphosis. OVERVIEW OF LITERATURE: LLIF is a minimally invasive interbody fusion technique; however, few reports compared the clinical outcomes of conventional PLIF and LLIF for degenerative lumbar kyphosis. METHODS: Radiographic data for patients who have undergone lumbar interbody fusion (≥3 levels) using PLIF or LLIF for degenerative lumbar kyphosis (lumbar lordosis [LL] <20°) were retrospectively examined. The following radiographic parameters were retrospectively evaluated preoperatively and 2 years postoperatively: segmental lordotic angle, LL, pelvic tilt (PT), pelvic incidence (PI), C7 sagittal vertical axis, and T1 pelvic angle. RESULTS: Nineteen consecutive cases with PLIF and 27 cases with LLIF were included. There were no significant differences in patients' backgrounds or preoperative radiographic parameters between the PLIF and the LLIF groups. The mean fusion level was 5.5±2.5 levels and 5.8±2.5 levels in the PLIF and LLIF groups, respectively (p=0.69). Although there was no significant difference in surgical times (p=0.58), the estimated blood loss was significantly greater in the PLIF group (p<0.001). Two years postoperatively, comparing the PLIF and LLIF groups, the segmental lordotic angle achieved (7.4°±7.6° and 10.6°±9.4°, respectively; p=0.03), LL (27.8°±13.9° and 39.2°±12.7°, respectively; p=0.006), PI–LL (19.8°±14.8° and 3.1°±17.5°, respectively; p=0.002), and PT (22.6°±7.1° and 14.2°±13.9°, respectively; p=0.02) were significantly better in the LLIF group. CONCLUSIONS: LLIF provided significantly better sagittal alignment restoration in the context of degenerative lumbar kyphosis, with less blood loss.
Animals ; Humans ; Incidence ; Kyphosis ; Lordosis ; Minimally Invasive Surgical Procedures ; Operative Time ; Retrospective Studies

STUDY DESIGN: Prospective cohort study. PURPOSE: This study aimed to identify risk factors for unplanned second-stage decompression for postoperative neurological deficit after indirect decompression using lateral lumbar interbody fusion (LLIF) with posterior fixation. OVERVIEW OF LITERATURE: Indirect lumbar decompression with LLIF has been used as a minimally invasive alternative to direct decompression to treat degenerative lumbar diseases requiring neural decompression. However, evidence on the prevalence of neurological deficits caused by spinal canal stenosis after indirect decompression is limited. METHODS: This study included 158 patients (mean age, 71.13±7.98 years; male/female ratio, 67/91) who underwent indirect decompression with LLIF and posterior fixation. Indirect decompression was performed at 271 levels (mean level, 1.71±0.97). Logistic regression analysis was used to identify the risk factors for postoperative neurological deficits. The variables included were age, sex, body mass index, presence of primary diseases, diabetes mellitus, preoperative motor deficit, levels operated on, preoperative severity of lumbar stenosis, and preoperative Japanese Orthopedic Association (JOA) score. RESULTS: Postoperative neurological deficit due to spinal canal stenosis occurred in three patients (1.9%). Spinal stenosis due to hemodialysis (p<0.001), ligament ossification (p<0.001), presence of preoperative motor paralysis (p<0.001), low JOA score (p=0.004), and severe canal stenosis (p=0.02) were significantly more frequent in the paralysis group. CONCLUSIONS: Severe preoperative canal stenosis and neurological deficit were identified as risk factors for postoperative neurological deterioration caused by spinal canal stenosis. Additionally, uncommon diseases, such as spinal stenosis due to hemodialysis and ligament ossification, increased the risk of postoperative neurological deficit; therefore, in such cases, indirect decompression is contraindicated.
Asian Continental Ancestry Group ; Body Mass Index ; Cohort Studies ; Constriction, Pathologic ; Decompression ; Diabetes Mellitus ; Humans ; Ligaments ; Logistic Models ; Orthopedics ; Paralysis ; Prevalence ; Prospective Studies ; Renal Dialysis ; Risk Factors ; Spinal Canal ; Spinal Stenosis

STUDY DESIGN: Prospective cohort study. PURPOSE: To identify factors that affect sagittal alignment correction in lateral lumbar interbody fusion (LIF) surgery for adult spinal deformity (ASD) and to investigate the degree of correction in each condition. OVERVIEW OF LITERATURE: LIF is a useful procedure for ASD, but the degree of correction can be affected by posterior osteotomy, intraoperative endplate injury, or anterior longitudinal ligament (ALL) rupture. METHODS: Radiographical data for 30 patients who underwent LIF for ASD were examined prospectively. All underwent two-stage surgery (LIF followed by posterior fixation). Radiographical parameters were measured preoperatively, after LIF, and after posterior fixation; these included the segmental lordotic angle, lumbar lordosis (LL), and other sagittal alignment factors. RESULTS: LL was corrected from 16.5°±16.7° preoperatively to 33.4°±13.8° after LIF (p<0.001) and then to 52.1°±7.9° following posterior fixation (p<0.001). At levels where Schwab grade 2 osteotomy was performed, the acquired segmental lordotic angles from the preoperative value to after posterior fixation and from after LIF to after posterior fixation were 19.5°±9.2° and 9.9°±3.9°, respectively. On average, 12.4° more was added than in cases without osteotomy. Endplate injury was identified at 21 levels (19.4%) after LIF, with a mean loss of 3.4° in the acquired segmental lordotic angle (5.3°±8.4° and 1.9°±5.9° without and with endplate injury, respectively). ALL rupture was identified at seven levels (6.5%), and on average 19.3° more was added in these cases between the preoperative and postoperative values than in cases without ALL rupture. CONCLUSIONS: LIF provides adequate sagittal alignment restoration for ASD, but the degree of correction is affected by grade 2 osteotomy, intraoperative endplate injury, and ALL rupture.

STUDY DESIGN: Retrospective case-control study.PURPOSE: We aimed to compare radiologic outcomes between posterior (PLIF) and lateral lumbar interbody fusion (LLIF) in short-level spinal fusion surgeries.OVERVIEW OF LITERATURE: Although LLIF enables surgeons to insert large lordotic cages, it is unknown whether LLIF more effectively corrects local and global sagittal alignments compared with PLIF in short-level spinal fusion surgeries.METHODS: Radiographic data acquired from patients with lumbar interbody fusion (≤3 levels) using PLIF or LLIF for degenerative lumbar diseases were analyzed. The following radiographic parameters were evaluated preoperatively and at 2 years postoperatively: segmental lordotic angle, disk height, lumbar lordosis (LL), pelvic tilt (PT), C7 sagittal vertical axis, and thoracic kyphosis (TK).RESULTS: In total, 144 patients with PLIF (193 fused levels) and 101 with LLIF (159 fused levels) were included. Patients’ backgrounds and preoperative radiographic parameters for any level of fusion did not differ significantly between PLIF and LLIF procedures. The LLIF group exhibited significantly greater changes at 1-level fusion compared to the PLIF group in the parameters of segmental lordotic angle (5.1°±5.8° vs. 2.1°±5.0°, p<0.001), disk height (4.2±2.3 mm vs. 2.2±2.0 mm, p<0.001), LL (7.8°±7.6° vs. 3.9°±8.6°, p=0.004), and PI–LL (−6.9°±6.8° vs. −3.6°±10.1°, p=0.03). While, a similar trend was observed regarding 2-level fusion, significantly greater changes were only observed in LL (12.1°±11.1° vs. 4.2°±9.1°, p=0.047) and PI–LL (−11.2°±11.3° vs. −3.0°±9.3°, p=0.043), PT (−6.4°±4.9° vs. −2.5°±5.3°, p=0.049) and TK (7.8°±11.8° vs. −0.3°±9.7°, p=0.047) in the LLIF group at 3-level fusion.CONCLUSIONS: LLIF provides significantly better local sagittal alignment than PLIF in 1- or 2-level fusion cases and improves spinopelvic alignment and local alignment for 3-level fusion cases. Thus, LLIF was demonstrated to be a useful lumbar interbody fusion technique, constituting a powerful tool for achieving sagittal realignment with minimal surgical invasiveness.
Animals ; Case-Control Studies ; Humans ; Kyphosis ; Lordosis ; Retrospective Studies ; Spinal Fusion ; Surgeons

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