Association of stromal type IV collagen and prognosis in neoadjuvant chemotherapy-treated pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear. METHODS: Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas. RESULTS AND CONCLUSIONS: Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.

Factors that interfere with immediate return to activity following volar locking plate fixation for distal radius fractures.

In the present study, the clinical findings that interfere with the immediate return to activity following volar locking plate (VLP) fixation for distal radius fractures were investigated. A total of 95 patients who underwent VLP fixation for distal radius fracture between July, 2014 and January, 2022 were divided into a good group (good score and outcome; n=86; 22 males and 64 females; median age, 61 years) and a poor group (poor score and outcome; n=8; 8 females; median age, 63.6 years) according to the quartiles of the disabilities of the arm, shoulder and hand (Q-DASH) score, at 1 month following VLP fixation. The duration from injury to surgery, the direction of fracture dislocation and radiographic parameters [radial inclination (RI), volar tilt (VT) and ulnar variance (UV)] at the time of injury were examined. Radiographic parameters (RI, VT and UV), the range of motion of the wrist joint, grip strength ratio and visual analog scale (VAS) at 1 month following VLP fixation were also examined. These parameters were compared among both groups. Moreover, logistic regression analysis was performed to determine whether these factors were independently associated with a poor Q-DASH score at 1 month following VLP fixation. At the time of injury, fracture displacement was significantly higher in the poor group (VT, -23.8˚; UV, 4.2 mm) than the good group (VT, -6.5˚; P=0.02; UV, 1.3 mm; P=0.01). No differences in the other parameters were observed between the groups. At 1 month following VLP fixation, the grip strength ratio (17.2%) in the poor group was significantly lower than that in the good group (43.8%, P<0.001), while the VAS score (5.6) in the poor group was significantly higher than that in the good group (2.4, P<0.001). Logistic regression analysis revealed that VT and UV at injury (P<0.05), grip strength ratio (P<0.001) and pain (VAS score) (P<0.001) were all independently associated with a poor Q-DASH score. On the whole, the present study suggests that large amounts of fracture displacement, weakness of grip strength and post-operative pain can be factors interfering with the return to activity immediately following VLP fixation.

Ultrastructural analysis of whole glomerulus using array tomography.

The renal glomerulus produces primary urine from blood plasma by ultrafiltration. The ultrastructure of the glomerulus is closely related to filtration function and disease development. The ultrastructure of the glomeruli has mainly been evaluated using transmission electron microscopy. However, the volume that can be observed using transmission electron microscopy is extremely limited relative to the total volume of the glomerulus. Consequently, observing structures that exist in only one location in each glomerulus, such as the vascular pole, and evaluating low-density or localized lesions are challenging tasks. Array tomography (AT) is a technique used to analyze the ultrastructure of tissues and cells via scanning electron microscopy of serial sections. In this study, we propose an AT workflow optimized for observing complete serial sections of the whole glomerulus, shared several analytical examples using the optimized AT workflow, and demonstrate the usefulness of this approach. Overall, this AT workflow can be a powerful tool for structural and pathological evaluation of the glomerulus. This workflow is also expected to provide new insights into the ultrastructure of the glomerulus and its constituent cells.

Chiba osteotomy (Tibial condylar valgus osteotomy) for a large tibial varus deformity: Technical note.

Chiba osteotomy is an effective technique for advanced knee osteoarthritis (KOA). The principle of the osteotomy is to correct both varus deformity and intra-articular joint congruity through an L-shaped osteotomy from the medial tibial condyle to the lateral intercondylar eminence. Previous studies have demonstrated that Chiba osteotomy is an effective method for alignment correction surgery for severe knee osteoarthritis. However, these reports slightly differ from the original concept of Chiba osteotomy. This report describes the pre-operative planning and surgical technique of Chiba osteotomy for patients with large tibial varus deformity, focusing on the management of early knee osteoarthritis following conditions such as post-traumatic Blount disease and "Pagoda" like proximal tibia varus deformities, as originally described. LEVEL OF EVIDENCE: IV.

Embryonic development and cranial ossification of the Japanese Aodaisho, Elaphe climacophora (Serpentes: Colubridae): with special reference to the prootic bone and auditory evolution in snakes.

Snakes show remarkably deviated "body plan" from other squamate reptiles. In addition to limb loss, they have accomplished enormous anatomical specialization of the skull associated with the pit organs and the reduction of the tympanic membranes and auditory canals in the outer ears. Despite being the most diverse group of snakes, our knowledge of the embryonic staging for organogenesis and cranial ossification has been minimal for Colubridae. Therefore, in the present observation, we provide the first embryonic description of the Japanese rat snake Elaphe climacophora. We based our study on the Standard Event System (SES) for external anatomical characters and on a description of the cranial ossification during post-ovipositional development. We further estimated the relative ossification timing of each cranial bony element and compared it with that of selected other snakes, lizards, turtles, and crocodilians. The present study shows that the relative ossification timing of the palatine and pterygoid bones is relatively early in squamates when compared to other reptiles, implying the developmental integration as the palate-pterygoid complex in this clade and functional demands for the unique feeding adaptation to swallow large prey with the help of their large palatine and pterygoid teeth. Furthermore, unlike in species with pit organs, the prootic bone of Ela. climacophora is expanded to provide articulation with the supratemporal, thereby contributing to the hearing system by detecting substrate vibration. We also demonstrate that the relative timing of the prootic ossification is significantly accelerated in colubrids compared to snakes with pit organs. Our finding suggests that the temporal changes of the prootic ossification underpin the evolution of the perception of the ground-bourne sound signals among snakes.

Callus formation after total hip arthroplasty using a short tapered-wedge stem.

OBJECTIVE: The incidence of periprosthetic fractures after total hip arthroplasty using a short tapered-wedge stem is high. Callus formation preceding this fracture, which indicates postoperative stress fracture around the stem, has been reported. However, previous studies on postoperative callus are limited. Hence, the current study aimed to evaluate the prevalence and risk factors of postoperative callus after total hip arthroplasty with a short tapered-wedge stem. MATERIALS AND METHODS: This retrospective study included 127 patients who underwent total hip arthroplasty using a cementless short tapered-wedge stem. The depth of stem insertion was measured as the distance from the lateral corner of the stem to the most medial point of the lesser trochanter along the body axis. Postoperative callus was defined as a bridging callus on the lateral femoral cortex at the distal end of the porous coating of the stem. Plain radiography was performed before surgery and immediately and at 1, 3, and 6 months after surgery to assess postoperative callus. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for PC. RESULTS: In total, 60 (47.2%) of 127 patients presented with postoperative callus. Multivariate logistic regression analysis with postoperative callus as the dependent variable revealed that the stem depth at 1 month after total hip arthroplasty (odds ratio, 1.14; 95% confidence interval, 1.04-1.24, p = 0.002) was a significant and independent risk factor of postoperative callus. CONCLUSION: Deep insertion of a short tapered-wedge stem is a risk factor for postoperative callus.

Finite element analysis of mechanical stress in a cementless tapered-wedge short stem in the varus position.

BACKGROUND: In recent years, the use of tapered-wedge short stems has increased due to their ability to preserve bones and tendons. Surgical techniques occasionally result in a varus position of the stem, which is particularly pronounced in short stems. Although the varus position is not clinically problematic, there are reports of an increased incidence of stress shielding and cortical hypertrophy. Thus, we evaluated and examined the acceptable range of varus angles using finite element analysis. METHODS: Patients diagnosed with osteoarthritis of the hip joint who had undergone arthroplasty were selected and classified into three types [champagne-flute (type A), intermediate (type B), and stovepipe (type C)]. Finite element analysis was performed using Mechanical Finder. The model was created using a Taperloc microplasty stem with the varus angle increased by 1° from 0° to 5° from the bone axis and classified into seven zones based on Gruen's zone classification under loading conditions in a one-leg standing position. The volume of interest was set, the mean equivalent stress for each zone was calculated. RESULTS: A significant decrease in stress was observed in zone 2, and increased stress was observed in zones 3 and 4, suggesting the emergence of a distal periosteal reaction, similar to the results of previous studies. In zone 2, there was a significant decrease in stress in all groups at a varus angle ≥ 3°. In zone 3, stress increased from ≥ 3° in type B and ≥ 4° in type C. In zone 4, there was a significant increase in stress at varus angles of ≥ 2° in types A and B and at ≥ 3° in type C. CONCLUSION: In zone 2, the varus angle at which stress shielding above Engh classification grade 3 may appear is expected to be ≥ 3°. Distal cortical hypertrophy may appear in zones 3 and 4; the narrower the medullary cavity shape, the smaller the allowable angle of internal recession, and the wider the medullary cavity shape, the wider the allowable range. Long-term follow-up is required in patients with varus angles > 3°.

Early Balloon Kyphoplasty Treatment for Osteoporotic Vertebral Fracture Reduces Adjacent Vertebral Fractures.

Background and Objectives: This study retrospectively examined whether the incidence rates of adjacent vertebral fractures (AVFs) can be reduced through balloon kyphoplasty (BKP) for osteoporotic vertebral fractures (OVFs) in the early stages, when there is little vertebral height variation. Materials and Methods: A total of 95 patients (22 males, 73 females, mean age: 80.7 years) who had undergone BKP were divided into two groups: the Early group (underwent BKP within 2 weeks after injury, n = 62), and the Non-early group (underwent BKP > 2 weeks after injury, n = 33). The following data were analyzed: patient characteristics; fracture level; the presence of old vertebral fractures, posterior wall injury, and intravertebral cleft; duration of surgery; duration of hospitalization; cement volume; the occurrence of AVF; the timing of AVF occurrence; Numerical Rating Scale (NRS) scores at the preoperative, postoperative, and final follow-up assessments; posterior vertebral kyphosis angle of the affected vertebra on plain lateral X-ray; vertebral wedge ratio; local kyphotic angle; and changes in posterior vertebral kyphosis angle, vertebral wedge ratio, and local kyphotic angle between preoperative and postoperative assessments. The patients were divided based on the occurrence or non-occurrence of AVF after BKP: the Non-AVF group, in which AVF did not occur, and the AVF group, in which AVF occurred. Results: The incidence of AVF was 15.8% (15/95 patients), with a notably lower incidence rate in the Early group at 6.5% (4/62 patients) compared to the Non-early group at 33.3% (11/33 patients). NRS scores significantly improved in both groups at the postoperative assessment and final follow-up. The changes in posterior vertebral kyphosis angle and vertebral wedge ratio were significantly lower in the Early group. In the Non-AVF group, the time from injury to surgery was significantly shorter. Conclusions: The Early group had a significantly lower incidence of AVF. The time from injury to surgery was a risk factor for AVF occurrence, suggesting that early BKP is recommended.

Association between smoking and duration of regional anesthesia - A propensity score matching study.

BACKGROUND: Previous studies have shown shorter duration of general anesthesia in smokers but it is unclear in regional anesthesia among smokers. We investigated the association between smoking status and the duration of regional anesthesia. METHODS: A total of 77 patients with a mean age of 47.3 years who underwent lower extremity orthopaedic surgery under regional anesthesia between January 2021 and June 2022 were enrolled. Sixteen patients were smokers and 57 patients were non-smokers. Propensity score matching was performed to balance patient characteristics. Our primary outcome was the time to onset of motor or sensory blockade and the duration required for full recovery of motor or sensory function. RESULTS: The time to sensory loss was 43.4 (SD 35.9) minutes in the smoking group and 39.6 (SD 31.7) minutes in the non-smoking group (p = 0.69), and the time to motor blockade was 37.0 (SD 28.4) minutes in the smoking group and 30.1 (SD 24.1) minutes in the non-smoking group (p = 0.35). The time for recovery of sensory function was 1146.7 (SD 197.8) minutes in the smoking group and 1024.6 (SD 177.9) minutes in the non-smoking group (p = 0.024). The time to recovery of motor function was 978.3 (SD 220.5) minutes in the smoking group and 1090.9 (SD 222.8) minutes in the non-smoking group (p = 0.08). The duration of sensory effect was significantly longer in the smoking group than in the non-smoking group. CONCLUSIONS: We found no significant association in the onset of regional anesthesia, but the duration of sensory blockade was significantly longer in the smoking group than in the non-smoking group. Hence, attention should be paid to the risks of the insensate limb in smokers due to prolonged sensory blockade as compared to non-smokers, rather than be concerned about delays in the onset of anesthesia.

Comparison of Conventional Incision and 10 mm Approach for Volar Locking Plates in Dorsal Displaced Distal Radius Fractures.

Introduction: The aim of this study was to investigate whether surgery with a 10 mm approach for volar locking plate fixation provides equivalent early post-operative outcomes to conventional incision surgery for distal radius fractures. Materials and Methods: The subjects were divided into a conventional incision group (mean age: 59.1 years, 8 males and 23 females) and a 10 mm approach group (mean age: 59.9 years of age, 6 males and 20 females). The wrist range of motion; grip strength; visual analog scale (VAS); quick disabilities of the arm, shoulder, and hand (Q-DASH) score; and modified Mayo score were assessed at 3 months after surgery. In addition, radial inclination, ulnar variance, and volar tilt were evaluated on post-operative radiography. Results: There was no significant difference between the groups in the wrist range of motion, grip strength, VAS, Q-DASH score, modified Mayo wrist score, and three parameters of post-operative radiography. All patients in both groups had no complications during the perioperative period. Conclusion: We found that a 10 mm approach obtained early post-operative outcomes and alignment comparable to conventional incision surgery for patients with dorsal displaced distal radius fractures.

A comprehensive review of cell transplantation and platelet-rich plasma therapy for the treatment of disc degeneration-related back and neck pain: A systematic evidence-based analysis.

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell- and platelet-rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in-human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2-year follow-up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell- and PRP-treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost-effectiveness assessments to determine the benefits of cell/PRP treatments.

Correlation of the total superoxide dismutase activity between joint fluid and synovium in end-stage knee osteoarthritis.

Recently, we found significantly reduced total superoxide dismutase (SOD) activity in the cartilage of patients with end-stage knee osteoarthritis (OA). In this study, we aimed to evaluate the SOD activity in serum, joint fluid, cartilage, and synovial membrane samples collected from 52 patients with end-stage knee OA who underwent total knee arthroplasty. The relationship between the total SOD activity in each tissue was evaluated using Spearman's rank correlation coefficient. The joint fluid total SOD activity was used as the objective variable, and its association with the serum, cartilage, and synovial total SOD activities was evaluated using multiple linear regression analysis. Univariate analysis revealed that joint fluid total SOD activity was positively correlated with synovial total SOD activity. Multiple linear regression analysis using joint fluid total SOD activity as the objective variable showed a positive association with synovial total SOD activity (ß = 0.493, adjusted R2 = 0.172, P < 0.01). In patients with end-stage knee OA, the state of the synovial total SOD activity is better reflected by the total SOD activity in the joint fluid than that in the cartilage. Joint fluid total SOD activity may serve as a biomarker for the treatment and prevention of synovitis.

A genome-wide association study identifies a locus associated with knee extension strength in older Japanese individuals.

Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10-8). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.

Variations in knee cartilage thickness: Fully automatic three-dimensional analysis of MRIs from five manufacturers.

BACKGROUND: Measurements of knee cartilage thickness derived from MR images are attractive biomarkers for osteoarthritis research. Although some cross-sectional multivendor studies exist, none have employed fully automatic three-dimensional MRI analysis. Our objective was to evaluate the variations in knee cartilage thickness measurements obtained using automated methods and MRI instruments from five different vendors. METHODS: The subjects were 10 healthy volunteers aged 22-60 years. MRI models with 3 Tesla strength from five different companies were used. Cartilage thickness was quantified fully automatically for seven regions. We hypothesized that "the MRI model influences cartilage thickness measurements." Inter-measurement error, defined as the absolute difference between the targeted and median thicknesses determined by the five MRI models, was analyzed using histograms. The factors generating the largest inter-measurement error were also examined. RESULTS: No exceptional trends attributable to a specific instrument model were observed, and the p-value from the Kruskal-Wallis test exceeded 0.05 in all seven regions. Therefore, the study hypothesis was rejected. Of the 350 measurements, the inter-measurement error was ≤0.05 mm in 53 %, ≤0.10 mm in 75 %, and ≤0.20 mm in 95 %. Analysis of the medial tibial cartilage, which had the largest inter-measurement error, revealed mis-extraction of synovial fluid as cartilage. CONCLUSIONS: The choice of MRI model did not influence cartilage thickness measurements. Overall, 95 % of the inter-measurement errors were within 0.20 mm. The greatest error resulted from mis-extracting synovial fluid as cartilage.

Autologous concentrated bone marrow injection for precollapse osteonecrosis of the femoral head concurrent with contralateral total hip arthroplasty: protocol for a clinical trial.

INTRODUCTION: The femoral head contralateral to the collapsed femoral head requiring total hip arthroplasty (THA) often manifests in the precollapse stage of osteonecrosis of the femoral head (ONFH). It is not yet demonstrated how autologous concentrated bone marrow injection may prevent collapse of the femoral head concurrent with contralateral THA. The primary objective is to evaluate the efficacy of autologous concentrated bone marrow injection for the contralateral, non-collapsed, femoral head in patients with bilateral ONFH, with the ipsilateral collapsed femoral head undergoing THA. METHODS AND ANALYSIS: This is a multicentre, prospective, non-randomised, historical-data controlled study. We will recruit patients with ONFH who are scheduled for THA and possess a non-collapsed contralateral femoral head. Autologous bone marrow will be collected using a point-of-care device. After concentration, the bone marrow will be injected into the non-collapsed femoral head following the completion of THA in the contralateral hip. The primary outcome is the percentage of femoral head collapse evaluated by an independent data monitoring committee using plain X-rays in two directions 2 years after autologous concentrated bone marrow injection. Postinjection safety, adverse events, pain and hip function will also be assessed. The patients will be evaluated preoperatively, and at 6 months, 1 year and 2 years postoperatively. ETHICS AND DISSEMINATION: This protocol has been approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University and Japan's Ministry of Healthy, Labour and Welfare and will be performed as a class III regenerative medicine protocol, in accordance with Japan's Act on the Safety of Regenerative Medicine. The results of this study will be submitted to a peer-review journal for publication. The results of this study are expected to provide evidence to support the inclusion of autologous concentrated bone marrow injections in the non-collapsed femoral head in Japan's national insurance coverage. TRIAL REGISTRATION NUMBER: jRCTc032200229.

Comparison of bioactive substances in novel-developed freeze-dried platelet-rich plasma (PRP) and activated normal PRP, and investigation of bioactive substance levels after long-term storage.

Introduction: In recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. Methods: Peripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor ß (TGF-ß), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. Results: In terms of the growth factors, the TGF-ß and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p < 0.05), while the bFGF levels were higher in VFD than in the LR-PRP and LP-PRP groups (p < 0.01). In terms of anti-inflammatory cytokines, the TIMP-1 level was lower in VFD than that in the other groups (p < 0.01), whereas the IL-1ra levels were higher in VFD than those in LP-PRP (p < 0.05) and lower than those in LR-PRP (p < 0.01). In terms of inflammatory enzymes and cytokines, the IL-1ra level was higher in VFD than that in LP-PRP (p < 0.05) and lower than that in LR-PRP (p < 0.01), whereas the IL-6 levels did not differ among the groups. Furthermore, the TGF-ß, bFGF, TIMP-1, and IL-1ra levels were 5.61 â†’ 3.38 (x103 pg/µL), 61.0 â†’ 63.0 (pg/µL), 3.4 â†’ 2.7 (x105 pg/µL), and 14.9 â†’ 14.5 (x103 pg/µL) at baseline and 1 year later, respectively. No significant differences in the BS levels were observed between baseline and 1 year after storage. Conclusions: The VFD samples prepared in this study exhibited higher levels of anti-inflammatory cytokines than LP-PRP and contained growth factor levels similar to LP-PRP and LR-PRP. In addition, the BS levels in VFD samples were maintained after one year of storage. These results suggest that VFD can be prepared and stored and may serve as a novel treatment strategy for sports injuries in high-risk groups, such as athletes.

Decreased grip strength is associated with paraspinal muscular oxidative stress in female lumbar degenerative disease patients.

We aimed to investigate the relationship between superoxide dismutase 2-related oxidative stress in the paraspinal muscles and spinal alignment, clinical skeletal muscle parameters, and mitochondrial function. Multifidus muscle samples from patients who underwent posterior lumbar surgery were analyzed. Patients with diseases affecting oxidative stress and spinal alignment were excluded. The superoxide dismutase 2 redox index was defined as the ratio of reactive oxygen species (superoxide) to antioxidant enzymes (superoxide dismutase 2) and was used as an index of oxidative stress. Patients were divided into two groups based on the superoxide dismutase 2 redox index. Spinal alignment, clinical skeletal muscle parameters, and succinic dehydrogenase (SDH) mean grayscale value were compared between the groups, with analyzes for both sexes. Multiple regression analyzes were used to adjust for the confounding effect of age on variables showing a significant difference between the two groups. Thirty-five patients with lumbar degenerative diseases were included. No significant differences were observed between the two groups for any of the parameters in males; however, females with a higher superoxide dismutase 2 redox index had greater lumbar lordosis, lower grip strength, and higher SDH mean grayscale value than those with a lower index. Multiple regression analyzes revealed that the superoxide dismutase 2 redox index was an independent explanatory variable for lumbar lordosis, grip strength, and SDH mean grayscale value in female patients. In conclusion, superoxide dismutase 2-related oxidative stress in the paraspinal muscles was associated with mitochondrial dysfunction and decreased grip strength in female lumbar degenerative disease patients.

Risk factors for nonresponse to 2 years of denosumab administration in patients with osteoporosis: A retrospective single-center cohorts study.

Background and Aims: To investigate the factors associated with changes in bone mineral density (BMD) and the incidence of fractures in osteoporotic patients treated with denosumab. Methods: This retrospective study included 162 osteoporotic patients treated with denosumab for 24 months between 2013 and 2019. Patients were divided according to the changes in BMD as nonresponders (NL group: <3% increase in lumbar spine BMD [LBMD], NH group: <0% increase in femoral neck BMD [FNBMD]) or responders (RL group: ≥3% increase in LBMD, RH group: ≥0% increase in FNBMD). Results: The respective changes in the LBMD and FNBMD after 24 months of denosumab treatment were 9.3% (95% confidence interval [CI]: 8.1-10.6) and 3.3% (95% CI: 2.1-4.5). Twenty-eight (17.3%) patients were in the NL group, and 134 (82.7%) were in the RL group. A history of bisphosphonate treatment was a risk factor for being in the NL group (odds ratio [OR]: 3.84, 95% CI: 1.38-10.71, p = 0.007; adjusted OR: 3.21, 95% CI: 1.01-10.19, p = 0.048). Although the NH (n = 48; 30.8%) and RH (n = 108; 69.2%) groups had similar baseline characteristics, the NH group had a significantly higher baseline FNBMD than the RH group (p = 0.003). The change in FNBMD was negatively associated with the FNBMD at baseline (r = -0.34, p < 0.001). No new osteoporotic fractures occurred in either group during follow-up. Conclusion: In osteoporotic patients receiving denosumab treatment, a history of bisphosphonate treatment was a risk factor for a lack of increase in LBMD, and a higher FNBMD at baseline was negatively associated with the change in FNBMD.