Early Postoperative Outcomes of Periprosthetic Femoral Fracture in Patients Over 90 Years of Age.

The number of total hip arthroplasty and bipolar hemiarthroplasty is increasing because of their good clinical outcomes and the aging population. Consequently, the incidence of periprosthetic femoral fractures (PFFs) is expected to increase in older patients with osteoporosis. Surgery is the first choice of treatment for PFF, except in Vancouver Type A fractures. However, surgical treatment of PFF, including open reduction and internal fixation (ORIF) and revision arthroplasty, is highly invasive, and high mortality rates have been reported. The indication for ORIF for PFF in very elderly patients at a high risk of complications remains controversial, and postoperative outcomes are uncertain. This study aimed to evaluate the postoperative outcomes of ORIF for PFF in elderly patients. We retrospectively analyzed four females with a mean age of 90.7 years (91-92 years) who underwent ORIF for PFF at our institution from September 2014 to January 2023. No cases of American Society of Anesthesiologists (ASA) grade 3 or higher were found. Three patients were classified as Vancouver Type B1, and one was classified as Vancouver Type C. Cementless stems were used in primary surgeries in all cases. To measure clinical outcomes, we investigated the patient's walking ability at 30 days, three months postoperatively, and the final follow-up. Mortality was assessed during the follow-up period. One patient could walk without walking aids preoperatively, two used a walking stick, and one used a walker. All patients remained hospitalized and underwent gait training with a walker at 30 days follow-up; however, at three months postoperatively and the final follow-up, no patient was unable to walk. No deaths occurred within one month of surgery. Three deaths occurred during follow-up: one within six months, one within one year, and one within five years of surgery. The postoperative ORIF results for PFF in patients aged > 90 years showed no fatal perioperative complications and low mortality within 30 days postoperatively. These results suggest that ORIF for PFF can be considered for elderly patients if the preoperative ASA grade is relatively low.

Comparison of the Anti-Inflammatory Effects of Mouse Adipose- and Bone-Marrow-Derived Multilineage-Differentiating Stress-Enduring Cells in Acute-Phase Spinal Cord Injury.

Abstract Spinal cord injury (SCI) is a serious neurological disorder, with the consequent disabilities conferred by this disorder typically persisting for life. Multilineage-differentiating stress-enduring (Muse) cells are endogenous stem cells that can be collected from various tissues as well as from mesenchymal stem cells (MSCs); additionally, these Muse cells are currently being used in clinical trials. The anti-inflammatory effect of stem cell transplantation prevents secondary injuries of SCI; however, its effect on Muse cells remains unclear. In this study, we aimed to compare the anti-inflammatory effects of adipose (AD)- and bone marrow (BM)-Muse cells that were isolated from mice (6-week-old C57BL/6J) following intralesional administration during the acute phase of SCI. Flow cytometry was used to isolate Muse cells from AD and BM MSCs. The percentage of Muse cells was 3.9 and 2.7% for AD and BM MSCs, respectively. To examine cell viability, Muse cells were incubated under H2O2-induced oxidative stress conditions. Overall, AD-Muse cells exhibited higher viability than BM-Muse cells (p = 0.032). In enzyme-linked immunosorbent assay analysis, AD-Muse cells displayed greater secretion of brain-derived neurotrophic factor (BDNF; p = 0.008), vascular endothelial growth factor (p = 0.032), and hepatocyte growth factor (p = 0.016). DNA microarray analysis revealed higher expression of Bdnf, neurotrophin-3 (Ntf3), nerve growth factor (Ngf), pleiotrophin (Ptn), and midkine (Mdk) in AD-Muse cells than in BM-Muse cells. To assess their anti-inflammatory effects in vitro, Muse cells and macrophages were co-cultured, and the levels of cytokines (tumor necrosis factor [TNF] α and interleukin [IL] 10) were measured in the medium. Consequently, we found that TNFα levels were lower in AD-Muse cells than in BM-Muse cells (p = 0.009), and IL10 levels were higher in AD-Muse cells than in BM-Muse cells (p = 0.008). Further, we induced moderate injuries via contusion of the spinal cord at the T10 level; Muse cells were transplanted intralesionally 7 days post-SCI. The number of surviving cells, alongside the number of CD86+ (M1 inflammatory effect), and CD206+ (M2 anti-inflammatory effect) macrophages in the spinal cord were measured 7 days post-transplantation. The number of surviving AD-Muse cells was higher than the number of surviving BM-Muse cells (ratio of AD-Muse/BM-Muse = 2.5, p > 0.05). The M1/M2 ratio in the AD-Muse cell-group (0.37) was lower than that in the control (phosphate-buffered saline) group (3.60, p = 0.008). The lesion area in the AD-Muse cell group was smaller than that in the BM-non-Muse (p = 0.049) and control groups (p = 0.012). As AD-Muse cells conferred a higher cell survival and neurotrophic factor secretion ability in vitro, AD-Muse cells demonstrated reduced inflammation after SCI. Overall, intralesional AD-Muse cell therapy is a potential therapeutic candidate that is expected to exhibit anti-inflammatory effects following acute SCI.

Intraperitoneal Administration of Etizolam Improves Locomotor Function in Mice After Spinal Cord Injury.

Neuroinflammation occurs in the acute phase of spinal cord injury (SCI) and inhibits neural regeneration. In mouse models, etizolam (ETZ) is a strong anxiolytic with unclear effects on SCI. This study investigated the effects of short-term administration of ETZ on neuroinflammation and behavior in mice after SCI. We administrated an ETZ (0.5 mg/kg) daily intraperitoneal injection from the day after SCI for 7 days. Mice were randomly divided into three groups (sham group: only laminectomy, saline group, and ETZ group). Inflammatory cytokine concentrations in the injured spinal cord epicenter were measured using an enzyme-linked immunosorbent assay on day 7 after SCI to evaluate spinal cord inflammation in the acute phase. Behavior analysis was performed the day before surgery and on days 7, 14, 28, and 42 after surgery. The behavioral analysis included anxiety-like behavior using the open field test, locomotor function using the Basso Mouse Scale, and sensory function using the mechanical and heat test. Inflammatory cytokine concentrations were significantly lower in the ETZ group than in the saline group in the acute phase after spinal surgery. After SCI, anxiety-like behaviors and sensory functions were comparable between the ETZ and saline groups. ETZ administration reduced neuroinflammation in the spinal cord and improved locomotor function. Gamma-amino butyric acid type A receptor stimulants may be effective therapeutic agents for patients with SCI.

Sex-Related Differences in Anxiety and Functional Recovery after Spinal Cord Injury in Mice.

It has been reported that female rats have a sex-related advantage in functional recovery and neuroprotection after spinal cord injury (SCI). However, the association between anxiety and neurological function after SCI in female and male rats remains unclear. The aim of this study was to examine sex-related differences in anxiety and neurological dysfunction after SCI in adult C57/BL6 male and female mice. After laminectomy at the 10th thoracic level, a contusive SCI was induced. The sham group received only a T10 laminectomy. Behavior testing (anxiety, motor/sensory function) was performed for 6 weeks after SCI. The spinal cord and preserved myelinated areas at the epicenter were histologically evaluated. Correlations between anxiety and motor/sensory function or histological parameters were analyzed using the Spearman correlation coefficient. Female and male mice showed significantly higher anxiety-like behaviors after SCI than before SCI. Anxiousness was significantly higher in female mice than in male mice after SCI. There was no significant difference in motor/sensory functions and histological features between the two groups. Anxiety-like behaviors were significantly correlated with sensory function at 2 weeks after SCI in female mice and with motor function at 2, 4, and 6 weeks after SCI in male mice. Anxiety-like behaviors were not significantly correlated with the spinal cord area at the epicenter in female and male mice. Our results revealed that female mice became more anxious than male mice after SCI. Anxiety-like behavior after SCI may be associated with functional recovery, and improving anxiety may affect functional recovery after injury.

Improvement in the results of the simple-foot-tapping test and cross-sectional area of the dural sac in patients with C5 palsy after posterior cervical spine surgery.

INTRODUCTION: The smaller cross-sectional areas of the dural sacs in patients without C5 palsy after posterior cervical spine surgery may lead to less neurological improvement. OBJECTIVES: The aim of this retrospective study was to clarify the differences in the cross-sectional area of the dural sac in the cervical spine and neurological improvement in patients with and without C5 palsy after posterior cervical spinal surgery. METHODS: We retrospectively evaluated the postoperative cross-sectional areas of the dural sacs and neurological outcomes in patients with and without C5 palsy after posterior cervical spine surgery. We compared the postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 on magnetic resonance images between the C5 palsy group (n = 19) and the no-C5 palsy group (n = 84) after posterior cervical spinal surgery 1 year postoperatively. Performance tests, namely, the 10-s grip-and-release test and the 10-s single-foot-tapping (FT) test, were compared between the two groups. RESULTS: Postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 (233.3 mm2 and 226.6 mm2, respectively) in the C5 palsy group were significantly larger (P = 0.0036 and P = 0.0039, respectively) than those (195.0 mm2 and 193.8 mm2, respectively) in the no-C5 palsy group. Postoperative gain in the grip-and-release test was similar between the two groups. Postoperative gain in the FT test (4.9 times) in the C5 palsy group was significantly larger (P = 0.0060) than that (1.8 times) in the no-C5 palsy group. CONCLUSIONS: In the C5 palsy group 1 year after posterior cervical spine surgery, the cross-sectional areas of the dural sac were larger, and the 10-s single FT test improved noticeably.

Neurotrophic Factor Secretion and Neural Differentiation Potential of Multilineage-differentiating Stress-enduring (Muse) Cells Derived from Mouse Adipose Tissue.

Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent stem cells that can be isolated based on stage-specific embryonic antigen-3 (SSEA-3), a pluripotent stem cell-surface marker. However, their capacities for survival, neurotrophic factor secretion, and neuronal and glial differentiation are unclear in rodents. Here we analyzed mouse adipose tissue-derived Muse cells in vitro. We collected mesenchymal stem cells (MSCs) from C57BL/6 J mouse adipose tissue and separated SSEA-3+, namely Muse cells, and SSEA-3-, non-Muse cells, to assess self-renewability; pluripotency marker expression (Nanog, Oct3/4, Sox2, and SSEA-3); spontaneous differentiation into endodermal, mesodermal, and ectodermal lineages; and neural differentiation capabilities under cytokine induction. Neurally differentiated Muse and non-Muse cell functions were assessed by calcium imaging. Antioxidant ability was measured to assess survival under oxidative stress. Brain-derived neurotrophic factor (BDNF), vascular endothelial cell growth factor (VEGF), and hepatocyte growth factor (HGF) secretion were analyzed in enzyme-linked immunosorbent assays. SSEA-3+ Muse cells (6.3 ± 1.9% of mouse adipose-MSCs), but not non-Muse cells, exhibited self-renewability, spontaneous differentiation into the three germ layers, and differentiation into cells positive for Tuj-1 (27 ± 0.9%), O4 (17 ± 3.4%), or GFAP (23 ± 1.3%) under cytokine induction. Neurally differentiated Muse cells responded to KCl depolarization with greater increases in cytoplasmic Ca2+ levels than non-Muse cells. Cell survival under oxidative stress was significantly higher in Muse cells (50 ± 2.7%) versus non-Muse cells (22 ± 2.8%). Muse cells secreted significantly more BDNF, VEGF, and HGF (273 ± 12, 1479 ± 7.5, and 6591 ± 1216 pg/mL, respectively) than non-Muse cells (133 ± 4.0, 1165 ± 20, and 2383 ± 540 pg/mL, respectively). Mouse Muse cells were isolated and characterized for the first time. Muse cells showed greater pluripotency-like characteristics, survival, neurotrophic factor secretion, and neuronal and glial-differentiation capacities than non-Muse cells, indicating that they may have better neural-regeneration potential.

Poor Motor-Function Recovery after Spinal Cord Injury in Anxiety-Model Mice with Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout.

Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1-/- mice) display anxiety-like behavior and altered γ-aminobutyric acid (GABA)A-receptor pharmacology. Here, we examined associations between anxiety and motor-function recovery in PRIP1-/- mice after a spinal cord injury (SCI) induced by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/- mice showed less distance than wild-type (WT) mice in the center 25% in an open field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in both WT and PRIP1-/- mice after SCI. WT and PRIP1-/- mice were completely paralyzed on day 1 after SCI, but gradually recovered until reaching a plateau at ∼4 weeks. After SCI, the PRIP1-/- mice had significantly greater motor dysfunction than the WT mice. In WT mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and velocity, and with the reaction time in a plantar pressure-sensitivity mechanical test. In PRIP1-/- mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and with the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expressions were elevated at the lesion epicenter in PRIP1-/- mice, and spinal cord atrophy and demyelination were more severe than in WT mice. The axonal fiber development was also decreased in PRIP1-/- mice, consistent with the poor motor-function recovery after SCI in these mice.