Effect of a Standardized Extract of Asparagus officinalis Stem (ETAS®50) on Cognitive Function, Psychological Symptoms, and Behavior in Patients with Dementia: A Randomized Crossover Trial.

Dementia is a disease of substantial national concern in a superaging society in Japan. Thus, the treatments targeting this disease are of high priority. However, pharmaceutical treatments are under development and invasive. Hence, many alternative treatments, which are less invasive, are tried, and some of them are supposed to work for dementia symptoms. ETAS®50 is one of these treatments. ETAS®50, a standardized extract of the Asparagus officinalis stem with heat shock protein-inducing activity, is a functional food. ETAS®50 has antistress, autonomic nerve regulation, and sleep quality improvement effects in humans and could contribute to relieving dementia symptoms. This double-blind crossover pilot trial aimed to examine the effects of ETAS®50. A total of 27 patients with mild-to-moderate dementia between October 2018 and February 2020 were included in the trial. ETAS®50 was consumed for 12 weeks and then a placebo for 12 weeks. A significant difference in the mean score of the severity of symptoms in the Neuropsychiatric Inventory Questionnaire (NPI-Q-a) was observed between the ETAS®50 period (0.56 ± 1.72 points) and placebo period (-0.67 ± 2.34 points) (p=0.045). Between-group comparisons with respect to the items of NPI-Q-a also showed a significant decrease in symptoms in the ETAS®50 period compared with the placebo period (p=0.015 for agitation and p=0.045 for depression). In addition, we observed that scores for apathy tended to improve in the ETAS®50 period (p=0.058).

Chondromodulin is necessary for cartilage callus distraction in mice.

Chondromodulin (Cnmd) is a glycoprotein known to stimulate chondrocyte growth. We examined in this study the expression and functional role of Cnmd during distraction osteogenesis that is modulated by mechanical forces. The right tibiae of the mice were separated by osteotomy and subjected to slow progressive distraction using an external fixator. In situ hybridization and immunohistochemical analyses of the lengthened segment revealed that Cnmd mRNA and its protein in wild-type mice were localized in the cartilage callus, which was initially generated in the lag phase and was lengthened gradually during the distraction phase. In Cnmd null (Cnmd-/-) mice, less cartilage callus was observed, and the distraction gap was filled by fibrous tissues. Additionally, radiological and histological investigations demonstrated delayed bone consolidation and remodeling of the lengthened segment in Cnmd-/- mice. Eventually, Cnmd deficiency caused a one-week delay in the peak expression of VEGF, MMP2, and MMP9 genes and the subsequent angiogenesis and osteoclastogenesis. We conclude that Cnmd is necessary for cartilage callus distraction.

An anterolateral dislocated monteggia lesion with plastic lateral bowing of the ulna associated with ipsilateral epiphyseal fracture of the distal radius: a case report with 4 years of follow-up.

We encountered a rare presentation of anterolateral dislocation of the radial head with plastic lateral bowing of the ulna associated with ipsilateral epiphyseal fracture of the distal radius in a child. The patient was treated surgically and reached skeletal maturity 4 years later with no functional or growth deficiency.

Overexpressed osteoactivin reduced osteoclastic callus resorption during distraction osteogenesis in mice.

Distraction osteogenesis is a widely used surgical technique to treat bone deformity and shortening. Several biological treatments have been studied to enhance bone formation during distraction osteogenesis in animals. However, role of osteoactivin in the osseous tissues during distraction osteogenesis remains poorly understood. In this animal experimental study, we investigated the spatiotemporal expression of osteoactivin by immunohistochemistry and real-time PCR using a mouse model for tibial lengthening. Furthermore, to address the role of osteoactivin in bone lengthening, we subjected the osteoactivin-transgenic mice to distraction osteogenesis model. During the lag phase, the fibroblast-like cells (possible progenitors of the osteoblasts or chondrocytes), which mainly express osteoactivin, were infiltrated into the osteotomy site. Osteoactivin was ubiquitously expressed in the lengthened segment during the distraction and consolidation phases. Consistent with the immunohistochemical analysis, the levels of the osteoactivin transcripts in the tibias were significantly increased throughout the distraction osteogenesis process. The bone mineral content in the osteoactivin-transgenic mice calculated using peripheral quantitative computed tomography was also significantly increased at the remodeling zone. The histomorphometric analysis revealed that newly formed callus resorption in the remodeling zone was significantly reduced but bone formation was not altered in the osteoactivin-transgenic mice. We conclude that osteoactivin functions as an inhibitor of callus resorption during the consolidation phase of distraction osteogenesis.

Surgical Mobilization of Skeletal Muscles Changes Functional Properties-Implications for Tendon Transfers.

PURPOSE: Tendon transfer surgery restores function by rerouting working muscle-tendon units to replace the function of injured or paralyzed muscles. This procedure requires mobilizing a donor muscle relative to its surrounding myofascial connections, which improves the muscle's new line of action and increases excursion. However, the biomechanical effect of mobilization on a donor muscle's force-generating function has not been previously studied under in vivo conditions. The purpose of this study was to quantify the effect of surgical mobilization on active and passive biomechanical properties of 3 large rabbit hind limb muscles. METHODS: Myofascial connections were mobilized stepwise from the distal end to the proximal end of muscles (0%, 25%, 50%, and 75% of muscle length) and their active and passive length-tension curves were measured after each degree of mobilization. RESULTS: Second toe extensor, a short-fibered muscle, exhibited a 30% decline in peak stress and 70% decline in passive stress, whereas extensor digitorum longus, a short-fibered muscle, and tibialis anterior, a long-fibered muscle, both exhibited similar smaller declines in active (about 18%) and passive stress (about 65%). CONCLUSIONS: The results highlight 3 important points: (1) a trade-off exists between increasing muscle mobility and decreasing force-generating capacity; (2) intermuscular force transmission is important, especially in second toe extensor, because it was able to generate 70% of its premobilization active force although most fibers were freed from their native origin; and (3) muscle architecture is not the major influence on mobilization-induced force impairment. CLINICAL RELEVANCE: These data demonstrate that surgical mobilization itself alters the passive and active force-generating capacity of skeletal muscles. Thus, surgical mobilization should not be viewed simply as a method to redirect the line of action of a donor muscle because this procedure has an impact on the functional properties of the donor muscle itself.

Insufficient Postoperative Rehabilitation in Patients with Both Proximal Femoral Fracture and Antecedent Mental Illness.

INTRODUCTION: Though a combination of proximal femoral fracture and mental illness is likely, the management of this combination is not well established. The aim of this study was to clarify the current disposition of acute care and rehabilitation for patients with this combination of conditions at our institution. METHODS: We retrospectively analyzed the records of 192 patients hospitalized in the psychiatric ward who present with a proximal femoral fracture and an antecedent mental illness. We investigated walking ability prior to injury and after surgery, at discharge from our institution, using the Functional Independence Measure (FIM) score. RESULTS: Although patients in the psychiatric ward demonstrated postoperative hospital stays approximately 10 days longer than those in the orthopedic ward, more than half of the patients in the psychiatric ward were discharged from our institution with a functional level of complete dependence for walking ability. In addition, nearly 90% of the patients studied were transferred to a psychiatric hospital where no physical therapy or rehabilitation was provided to the inpatients. CONCLUSIONS: At our institution, patients with proximal femoral fracture and antecedent mental illness tended to be discharged with complete dependence in walking ability, often to a psychiatric hospital without physical therapy or rehabilitation. We hope this paper will draw attention to the need for rehabilitation in these patients.

Gustilo Type III Open and Comminuted Tibial Fractures Managed by Simultaneous Combination of a Free Latissimus Dorsi Muscle Flap and Ilizarov External Fixation: A Case Report.

CASE: A 70-year-old woman who sustained Gustilo type III open and comminuted tibial fractures presented with extensive soft-tissue defect. Definitive surgery was performed using a free latissimus dorsi muscle flap for the extensive soft-tissue defect and Ilizarov external fixation (IEF) to stabilize the fractures and arthrodese the ankle. Ankle arthrodesis was accomplished by the wires penetrating the implanted muscle flap. CONCLUSION: The combined free flap and IEF management protocol described in this report was effective in achieving early weight-bearing and prompt bone healing in an elderly patient with poor bone quality and extensive open and comminuted fractures.

Morphological alterations of the tendon and pulley on ultrasound after intrasynovial injection of betamethasone for trigger digit.

PURPOSE: The aim of this study was to elucidate whether intrasynovial corticosteroid injections for trigger digit reduced the volume of the tendon and pulley on high-resolution ultrasonography. METHODS: Twenty-three digits of 20 patients with trigger digit were included. Each affected finger was graded clinically according to the following classification: grade I for pre-triggering, grade II for active triggering, grade III for passive triggering, and grade IV for presence of contracture. Axial ultrasound examinations were performed before an intrasynovial corticosteroid injection and at an average of 31 days after the injection. The transverse diameter, thickness, and cross-sectional area of the tendon and the thickness of the pulley were measured by two independent, blinded researchers. RESULTS: At least 1 grade of improvement was achieved in this study group by the time of the second examination. The transverse diameter and cross-sectional area of the tendon and the thickness of the pulley significantly decreased (P<0.05). CONCLUSION: The injection of a single dose of betamethasone improved clinical symptoms by reducing the volume of both the tendon and pulley, which may be related to the fact that tendon and pulley ruptures are delayed by corticosteroid injections.

Molecular insights into the non-recombining nature of the spinach male-determining region.

Spinach (Spinacia oleracea L.) is a dioecious plant with male heterogametic sex determination and homomorphic sex chromosomes (XY). The dioecism is utilized for producing commercial hybrid seeds, and hence understanding the molecular-genetic basis of the species' sex determining locus is an important issue for spinach breeding. In this study, seven dominant DNA markers were shown to completely co-segregate with the male-determining gene in segregating spinach populations comprising > 1500 plants. In addition, these seven dominant DNA markers were completely associated with the male-determining gene in over 100 spinach germplasm accessions and cultivars. These observations suggest that, in spinach, a Y-chromosomal region around the male-determining locus does not (or almost not) recombine with a counterpart region on the X chromosome. Using five of the seven DNA markers, five bacterial artificial chromosome (BAC) clone contigs with a total length of approximately 690 kbp were constructed. Full sequencing of six representative BAC clones (total insert length 504 kbp) from the five contigs and a transcriptome analysis by RNA-seq revealed that the Y-chromosomal region around the male-determining locus contains large amounts of repetitive elements, suggesting that the region might be poor in gene content. Most of the repeats found in this region are novel Ty1-copia-like and its derivative elements that accumulate predominantly in heterochromatic regions. Our findings may provide valuable insight into spinach genome structure and clues for future research into the evolution of the sex determining locus.

Pedicled unipolar latissimus dorsi flap for reconstruction of finger extensor.

We describe the use of a pedicled unipolar latissimus dorsi flap to restore finger extension. The patient had large defects in the radial nerve and extensor musculature. A long-tailed, 50-cm-long flap was prepared, which enabled the end of the flap to be sutured to the extensor digitorum.

Radiographic changes of cervical destructive spondyloarthropathy in long-term hemodialysis patients: A 9-year longitudinal observational study.

Analyses of radiographic changes and clinical symptom of destructive spondyloarthropathy (DSA) on consecutive 42 patients managed with long-term hemodialysis were performed to elucidate radiographic changes of DSA and the factors that influence to the destructive changes. Patients underwent plain radiographs of the cervical spine with 9 years interval. Grading of radiological feature from lateral view was classified into grade 0 to grade 3. Clinical symptom was evaluated using modified Japanese Orthopaedic Association scoring system for cervical myelopathy (mJOA score). Destructive changes were observed in 3 patients at the first examination, and those were observed in 15 patients 9 years after the first examination. There is no statistically significant difference between the duration of hemodialysis and the grade. The mean age at the onset of hemodialysis, however, was significantly higher in patients of grade 2 and 3 than those of grade 1. Older patients with long-term hemodialysis had destructive changes. Destructive changes commonly observed in lower cervical spine. The average numbers of the involved disc level were 1.6 in grade 2 and 1.0 in grade 3. Clinical symptoms were varied in each grade and there was no statistically significant difference in total mJOA score among these grades. J. Med. Invest. 64: 68-73, February, 2017.

Clinical utility of the 6-min walk test for patients with moderate Parkinson's disease.

The aim of this study was to test the clinical utility of the 6-min walk test (6MWT) for patients with moderate Parkinson's disease (PD) through a determination of factors related to this test. This was a descriptive, observational study carried out at a General Hospital, in-patients. Twenty-four patients with moderate PD were studied. We used Hoehn and Yahr stage ratings (HY stage), Unified Parkinson Disease Rating Scales (UPDRS) motor examination score, 6MWT, Berg Balance scale, Timed 'Up & Go' test (TUG), 10-m walk test (10-m walk speed, 10-m walk steps and cadence), and the energy cost of walking (Ec). The average HY stage was 3.1±0.5 and 6MWT was 340.8±110.9 m. TUG (r=-0.68, P<0.01) and Ec (r=-0.65, P<0.01) were correlated significantly with 6MWT. Multiple regression analysis with age, HY stage, TUG, cadence, and Ec as variables indicated a significant degree of variability in the 6MWT results (R=0.77, P<0.001). The TUG (ß=-0.47, P<0.01) and Ec (ß=-0.4, P<0.01) were correlated independently with the 6MWT results. In contrast, age, HY stage, and cadence were not independently correlated. The 6MWT is a simple tool for assessing walking capacity for patients with PD. In this study, we confirmed the convergent validity and clinical utility of the 6MWT for patients with moderate PD. The 6MWT is useful for clinical assessment to guide the planning of rehabilitation treatment for patients with moderate PD.

Forearm lengthening by distraction osteogenesis: A report on 5 limbs in 3 cases.

Radioulnar length discrepancy causes pain and decreases function of the wrist, forearm, and elbow. Limb lengthening, which has been used in the treatment of various deformities of the forearm, is necessary to restore balance between the ulna and radius. We treated 5 limbs in 3 patients (2 boys, 1 girl; mean age 9.3 years old) with radioulnar length discrepancy by distraction osteogenesis of either the ulna or radius using external fixators. We dissected the interosseous membrane between the ulna and radius in 3 limbs in 2 cases and did not do so in 2 limbs of 1 case. These cases include 2 cases with hereditary multiple exostoses, and 1 case with multiple epiphyseal dysplasia. The results were investigated and evaluated in this study, using appropriate clinical and radiographic parameters, noting the state of the interosseous membrane, which has an important role in forearm stability. The mean fixation period was 113 days. The mean distraction distance was 22.8 mm. The mean follow-up period was 637.7 days. The mean ulnar shortening and radial articular angle respectively improved from 7.4 mm and 30.2° preoperatively to -0.1 mm and 34.8° postoperatively. Balance between the ulna and radius was restored, and the results showed significant improvements in range of motion of the joints. However, 2 unintended radial head subluxations occurred in 2 limbs without dissection of the interosseous membrane. In addition, a keloid remained in 1 limb due to pin site infection. Forearm lengthening by distraction osteogenesis was useful in our cases. It is important to recognize the function of the interosseous membrane when lengthening is performed by osteotomy of the proximal ulna by gradual distraction with an external fixator.

Local administration of zoledronic acid for giant cell tumor of bone.

Giant cell tumor of bone is a locally aggressive tumor with a high local recurrence rate. Several adjuvant therapies have been employed to reduce the recurrence rate, but their effectiveness remains controversial. The authors attempted local administration of zoledronic acid, a nitrogen-containing bisphosphonate that strongly inhibits bone resorption, as an adjuvant treatment for histologically proven giant cell tumor of bone in 5 patients at their institution. After biopsy, 4 patients were treated with local administration of zoledronic acid with artificial bone and 1 was treated with zoledronic acid without artificial bone. Histologic response to the treatment was evaluated with surgically resected specimens. The 4 patients treated with artificial bone showed local control, with histologic tumor necrosis rates of 90%, 90%, 50%, and 10%. Magnetic resonance imaging showed poor gadolinium enhancement, and histologic examination after local zoledronic acid treatment showed tumor necrosis. One patient without artificial bone showed no histologic tumor necrosis and had local recurrence in soft tissue 18 months after tumor resection. A 3-week waiting period between biopsy and zoledronic acid treatment appears reasonable from the histological study. Complication of this therapy was delayed wound healing and it occurred in 2 cases. Taken together, this case series suggests that local administration of zoledronic acid with artificial bone is a potential adjuvant therapy for giant cell tumor of bone. On the other hand, effective local administration of zoledronic acid requires some bone matrix, including artificial bone. Campanacci's grading is important for predicting the effect of local administration of zoledronic acid.

Osteoactivin attenuates skeletal muscle fibrosis after distraction osteogenesis by promoting extracellular matrix degradation/remodeling.

The aim of this study was to determine whether osteoactivin attenuated skeletal muscle fibrosis caused by distraction osteogenesis. Tibial osteotomies were performed on wild-type and osteoactivin-transgenic (OA-Tg) mice, and tibiae were distracted for 2 weeks. Ankle plantar flexion torque and the gastrocnemius muscles were analyzed. The amount and area of collagenous tissue and the passive torque were reduced in the OA-Tg group at 8 weeks after osteotomy. Transcript levels of matrix metalloprotease (mmp)-3 and MMP-9 were upregulated, and MMP-3 and MMP-9 proteins were increased in the OA-Tg group. Osteoactivin-mediated increase in MMPs may attenuate skeletal muscle fibrosis.

Osteomyelitis Caused by Candida glabrata in the Distal Phalanx.

Osteomyelitis caused by Candida glabrata is rare and its optimal treatment is unknown. Here we report a case of osteomyelitis caused by C. glabrata in the distal phalanx in a 54-year-old woman. Despite partial resection of the nail and administering a 1-month course of antibiotics for paronychia, the local swelling remained and an osteolytic lesion was found. C. glabrata osteomyelitis of the distal phalanx was later diagnosed after curettage. Thereafter, the patient was treated with antifungal agents for 3 months. The infection eventually resolved, and radiological healing of the osteolytic lesion was achieved. Antifungal susceptibility testing should be performed in the case of osteomyelitis caused by nonalbicans Candida species, due to their resistance to fluconazole.

State of the art: Transforaminal approach for percutaneous endoscopic lumbar discectomy under local anesthesia.

Minimally invasive percutaneous endoscopic discectomy (PED) with a transforaminal approach under local anesthesia was started in the late 20th century. As the procedure requires a skin incision of only 8 mm, it is the least invasive disc surgery procedure at present, and owing to advances in instruments and optics, the use of this technique has gradually spread. In Japan, Dr. Dezawa from Teikyo University Mizonokuchi Hospital introduced this technique in 2003. Thanks to his efforts, the number of surgeons who can perform PED has increased, although the number of active PED surgeons is still only around 20. The first author (K.S.) started PED in 2010. In this review article, we explain the state-of-the-art PED transforaminal technique for minimally invasive disc surgery and present three successful cases.

The state of the art in arthroscopic hip surgery.

Hip arthroscopy is among the most rapidly evolving arthroscopic techniques in the last decade and offers the benefits of being both a minimally invasive procedure and an excellent diagnostic tool. Improvements in instrumentation and surgical skills have advanced our ability to accurately diagnose and treat various conditions of the hip joint, and hip arthroscopy has elucidated several pathologies that cause disabling symptoms. Many of these conditions were previously unrecognized and left untreated. The indications for hip arthroscopy include the management of early osteoarthritis, synovial disorders (e. g., synovial osteochondromatosis), labral tears, chondral lesions, and femoroacetabular impingement (FAI), which is increasingly recognized as a disorder that can lead to the development of early cartilage and labral injury. A better understanding of hip arthroscopy, including the anatomy, improved surgical techniques, indications, and complications of the procedure, is essential for its success. This review article discusses the state of the art of arthroscopic hip surgery.

State of the art: Elbow arthroscopy: review of the literature and application for osteochondritis dissecans of the capitellum.

Elbow arthroscopy has become a safe and effective treatment option for a number of elbow disorders. The most rewarding and successful indication is the removal of loose bodies. Loose bodies are often a result of osteochondritis dissecans (OCD) of the capitellum, and arthroscopy in this case is useful for performing debridement, thereby eliminating the need for a more extensive open procedure associated with complications. In this review, we describe our arthroscopic technique for OCD of the capitellum. We usually conduct arthroscopy in the supine position, and use 2.9-mm arthroscopes of 30° and 70°. The 70° arthroscope provides a greater operative field than the 30° arthroscope. Arthroscopic treatment for OCD may require 2 anterior and 2 posterior portals. Loose bodies are commonly found in the radial fossa, coronoid fossa, and in the olecranon fossa. Once the loose bodies are removed, all unstable cartilage of the capitellum lesion is removed to create a stable bed. If any sclerotic changes to the lesion bed are observed, we create microfractures in the lesion bed. The most significant complication in arthroplasty is neurovascular injury. However, we have never experienced this devastating complication, which can be avoided by paying careful attention to detail.

Hypertrophic chondrocytes in the rabbit growth plate can proliferate and differentiate into osteogenic cells when capillary invasion is interposed by a membrane filter.

The fate of hypertrophic chondrocytes during endochondral ossification remains controversial. It has long been thought that the calcified cartilage is invaded by blood vessels and that new bone is deposited on the surface of the eroded cartilage by newly arrived cells. The present study was designed to determine whether hypertrophic chondrocytes were destined to die or could survive to participate in new bone formation. In a rabbit experiment, a membrane filter with a pore size of 1 µm was inserted in the middle of the hypertrophic zone of the distal growth plate of ulna. In 33 of 37 animals, vascular invasion was successfully interposed by the membrane filter. During 8 days, the cartilage growth plate was enlarged, making the thickness 3-fold greater than that of the nonoperated control side. Histological examination demonstrated that the hypertrophic zone was exclusively elongated. At the terminal end of the growth plate, hypertrophic chondrocytes extruded from their territorial matrix into the open cavity on the surface of the membrane filter. The progenies of hypertrophic chondrocytes (PHCs) were PCNA positive and caspase-3 negative. In situ hybridization studies demonstrated that PHCs did not express cartilage matrix proteins anymore but expressed bone matrix proteins. Immunohistochemical studies also demonstrated that the new matrix produced by PHCs contained type I collagen, osteonectin, and osteocalcin. Based on these results, we concluded that hypertrophic chondrocytes switched into bone-forming cells after vascular invasion was interposed in the normal growth plate.