First Clinical Report on the Treatment of Parkinson's Disease with Fetal Midbrain Precursor Cells.

BACKGROUND: Because human fetal ventral mesencephalic tissue grafts provide promising results in ameliorating Parkinson's disease-implicated motor dysfunctions, human fetal midbrain-derived dopamine neuronal precursor cells are considered good candidates for cell-based therapy for Parkinson's disease in that large quantities of cells can be supplied through a good manufacturing practice-compliant system. OBJECTIVE: We conducted a prospective, phase I/IIa, dose-escalation, open-label "first-in-human" clinical trial with fetal neural precursor cells to assess their safety and therapeutic efficacy in patients with idiopathic Parkinson's disease. METHODS: Fifteen patients were assigned to receive three different doses of cells (4 × 106 , 12 × 106 , and 40 × 106 cells) and completed a 12-month follow-up. The primary outcome was safety, by measuring the presence of grade 3 or higher cells according to National Cancer Institute guidelines and any contaminated cells. Secondary outcomes assessed motor and neurocognitive function, as well as the level of dopamine transporters, by positron emission tomography-computed tomography. RESULTS: Although a pronation-supination and hand/arm movement performance was remarkably enhanced in all three groups (all P < 0.05), the medium- and high-dose-treated groups exhibited significant improvement in Unified Parkinson's Disease Rating Scale Part III only up to 26.16% and 40%, respectively, at 12 months after transplantation without any serious clinical complications or graft-induced dyskinesia in all patients. However, the motor improvements did not correlate with increase in the dopamine transporter on positron emission tomography images. CONCLUSIONS: Our results primarily demonstrate the safety and plausible dose-dependent efficacy of human fetal midbrain-derived dopamine neuronal precursor cells for idiopathic Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society.

Xenogeneic transplantation of mitochondria induces muscle regeneration in an in vivo rat model of dexamethasone-induced atrophy.

Muscle atrophy significantly impairs health and quality of life; however, there is still no cure. Recently, the possibility of regeneration in muscle atrophic cells was suggested through mitochondrial transfer. Therefore, we attempted to prove the efficacy of mitochondrial transplantation in animal models. To this end, we prepared intact mitochondria from umbilical cord-derived mesenchymal stem cells maintaining their membrane potential. To examine the efficacy of mitochondrial transplantation on muscle regeneration, we measured muscle mass, cross-sectional area of muscle fiber, and changes in muscle-specific protein. In addition, changes in the signaling mechanisms related to muscle atrophy were evaluated. As a result, in mitochondrial transplantation, the muscle mass increased by 1.5-fold and the lactate concentration decreased by 2.5-fold at 1 week in dexamethasone-induced atrophic muscles. In addition, a 2.3-fold increase in the expression of desmin protein, a muscle regeneration marker, showed a significant recovery in MT 5 µg group. Importantly, the muscle-specific ubiquitin E3-ligases MAFbx and MuRF-1 were significantly decreased through AMPK-mediated Akt-FoxO signaling pathway by mitochondrial transplantation compared with the saline group, reaching a level similar to that in the control. Based on these results, mitochondrial transplantation may have therapeutic applications in the treatment of atrophic muscle disorders.

Clinical Applicability and Psychometric Properties of Manual Function Test for Patients with Stroke.

The Manual Function Test (MFT) is a tool to assess upper extremity motor impairment associated with stroke. This study investigated psychometric properties of the Korean version of the MFT and to establish normative data. Eighty-one patients were enrolled to evaluate MFT, Fugl-Meyer Assessment (FMA) and manual muscle test (MMT). MFT was completed by eight raters on two occasions separated by 6 weeks. Absolute and relative reliability and validity were examined. Additionally, MFT was assessed on 75 healthy controls of different ages. Intraclass correlation coefficient (ICC) (2,1) values for total and each dimension of Korean MFT ranged from 0.984 to 0.998 in the affected side of hemiplegic patients, indicating inter-rater reliability. Percentage values of standard error of measurement (SEM) and smallest real difference (SRD) ranged 3.10-10.57% and 8.58-29.29% respectively. Test-retest reliability ICCs for all raters were above 0.98. Effect size (ES) and standardized response mean (SRM) were larger in the acute-subacute group (onset to initial evaluation ≤ 4 months) (ES = 0.12; SRM = 0.41) than those in the chronic group (onset to evaluation > 4 months) (ES = 0.01; SRM = 0.11). MFT score was significantly correlated with FMA score (p < 0.001) and MMT score (p < 0.001). In healthy controls, regression analysis indicated that age significantly predicts manual function scores on both dominant and non-dominant. The Korean MFT showed good reliability and validity. Modest responsiveness was observed in patients evaluated early after stroke onset. The Korean MFT is useful in evaluating upper extremity motor deficits for clinical and research purposes.

Efficacy of low dose gabapentin in acute herpes zoster for preventing postherpetic neuralgia: a prospective controlled study.

Postherpetic neuralgia (PHN) is a sequela of herpes zoster that adversely affects quality of life seriously. The risk factors for PHN are well known but the effective interventions that reduce the incidence of PHN are less studied. The objective of this study is to evaluate the efficacy of treatment with gabapentin in patients with acute herpes zoster for preventing PHN. We performed a prospective randomized controlled study of 120 participants diagnosed with acute herpes zoster, aged 50 and over and complaining moderate to severe pain. All patients were treated with valacyclovir and acetaminophen. Half of the participants were assigned to the gabapentin group and received gabapentin 300 mg three times a day additionally. The intensity of pain at every visit and the incidence of PHN in both groups were measured. Total 52 and 49 patients in the gabapentin group and the control group, respectively, had completed 12 weeks of follow-up period. Although the incidence of PHN was higher in the control group, the difference was not statistically significant (6.1% vs. 3.8%, p = 0.67). Our results indicate that the use of low-dose gabapentin in acute herpes zoster seems not effective in the prevention of PHN.

Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial.

Allogeneic umbilical cord blood (UCB) has therapeutic potential for cerebral palsy (CP). Concomitant administration of recombinant human erythropoietin (rhEPO) may boost the efficacy of UCB, as it has neurotrophic effects. The objectives of this study were to assess the safety and efficacy of allogeneic UCB potentiated with rhEPO in children with CP. Children with CP were randomly assigned to one of three parallel groups: the pUCB group, which received allogeneic UCB potentiated with rhEPO; the EPO group, which received rhEPO and placebo UCB; and the Control group, which received placebo UCB and placebo rhEPO. All participants received rehabilitation therapy. The main outcomes were changes in scores on the following measures during the 6 months treatment period: the gross motor performance measure (GMPM), gross motor function measure, and Bayley scales of infant development-II (BSID-II) Mental and Motor scales (18). F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images (DTI) were acquired at baseline and followed up to detect changes in the brain. In total, 96 subjects completed the study. Compared with the EPO (n = 33) and Control (n = 32) groups, the pUCB (n = 31) group had significantly higher scores on the GMPM and BSID-II Mental and Motor scales at 6 months. DTI revealed significant correlations between the GMPM increment and changes in fractional anisotropy in the pUCB group. 18F-FDG-PET/CT showed differential activation and deactivation patterns between the three groups. The incidence of serious adverse events did not differ between groups. In conclusion, UCB treatment ameliorated motor and cognitive dysfunction in children with CP undergoing active rehabilitation, accompanied by structural and metabolic changes in the brain.

Reliability of fractional anisotropy measurement for children with cerebral palsy.

OBJECTIVE: Periventricular leukomalacia (PVL) is the leading cause of disability in children with cerebral palsy (CP). Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique for detecting microstructural lesions of white matter. Fractional anisotropy (FA) is a widely used DTI index with clinical significance in children with CP. This study aims to estimate the reliability of FA for children with CP. DESIGN: Four observers measured FA values in 78 children with spastic CP from PVL. Region of interests (ROIs) were placed in three anatomical loci at each side: medial and lateral portions of posterior limb of internal capsule and ascending sensory tract. Intra- and interobserver reliability indices including intraclass correlation coefficient (ICC), standard error of measurement, smallest real difference percentage (SRD%), and limit of agreement using Bland-Altman analysis were examined. RESULTS: Intraobserver ICCs were 0.85 or greater in all ROIs, and SRD% ranged from 3.59 to 12.33%. Interobserver ICCs exceeded 0.90 in all ROIs, and the SRD% were less than 10%. The Bland-Altman analysis showed good intra- and interobserver agreements. The reliability was not affected by severity of impairment. CONCLUSIONS: Reliability of DTI-derived FA value using ROIs was satisfactory in children with PVL.

Paraspinal muscles atrophy on both sides and at multiple levels after unilateral lumbar partial discectomy.

To identify the changes in cross-sectional areas (CSAs) and fatty infiltration of both sides of the paravertebral muscles and their associations with prognostic factors in patients who underwent unilateral lumbar discectomy. We retrospectively reviewed 27 patients who underwent magnetic resonance imaging before and after 1- or 2-level lumbar discectomy. The CSAs and functional cross-sectional areas of the paraspinal muscles were bilaterally measured from L1 to L2 to L5 to S1 based on T2-weighted axial images. These parameters were compared pre-and postoperatively. CSAs and functional cross-sectional areas decreased also in non-operative, non-surgical levels, not only in operated levels after discectomy. In the correlation analysis, the CSA of psoas major muscle at L1 to L2 was significantly decreased in patients with lower preoperative lordosis (r = 0.598, P = .040). The postoperative CSA of psoas major muscle at L4 to L5 was lower in those with the higher Pfirrmann grade (r = -0.590, P = .002); however, the CSA of quadratus lumborum muscle at L1 to L2 showed the opposite result (r = 0.526, P = .036). Similar results were also observed in the partial correlation adjusted for age and postoperative duration. Patients who underwent discectomy experienced overall paraspinal muscle atrophy in the lumbar region, including surgical and non-surgical sites. Such atrophic changes emphasized the need for core strengthening and lumbar rehabilitation from the early period after partial discectomy.

Maintenance of the synergistic effects of cord blood cells and erythropoietin combination therapy after additional cord blood infusion in children with cerebral palsy: 1-year open-label extension study of randomized placebo-controlled trial.

BACKGROUND: This 1-year open-label extension study aimed to identify the persistent synergistic effects of allogeneic umbilical cord blood (UCB) cells and erythropoietin (EPO) in children with cerebral palsy (CP) for up to 2 years. METHODS: This open-label extension study followed children with CP who were enrolled in the previous randomized, double blind, placebo-controlled trial. The following groups from the first trial were maintained: (A) UCB + EPO, (B) UCB, (C) EPO, and (D) only placebo, and all the participants had continued active rehabilitation. This extended study started 3 months after termination of the first trial, which had a 1-year follow-up duration. All subjects received single additional UCB intravenous infusion at the extension baseline regardless of their initial allocation. Outcome measures were the gross motor performance measure (GMPM), gross motor function measure-66 (GMFM-66), and Bayley scales of infant development-II (BSID-II), which were followed at 3, 6, and 12 months after the extension baseline. Changes in the outcome scores from the baseline values of the previous trial and this study were analysed. RESULTS: Sixty-nine children (4.29 ± 1.28 years, M:F = 34:35) were included in this study. Each group showed improvements in the outcome measures at 12 months after additional UCB infusion compared to the baseline scores, except for GMFM and GMPM in Group C which were elevated at 3 and 6 months post-therapy. Total subject analyses did not show significant differences in the outcome measures between the four different groups at 3, 6 and 12 months after additional UCB therapy. However, patients with severe dysfunction, whose GMFCS levels were IV and V, revealed a larger improvement of the GMPM score in Group A than in Group D (Ps < 0.05) from the baseline value of the previous trial. The changes in BSID-II mental scale scores were positively correlated with the number of administered total nucleated cells per unit body weight during this one-year extension study period (r = 0.536, P = 0.001). CONCLUSIONS: These results suggest that when administering UCB to treat patients with CP, combination therapy with EPO is more effective, and the effect might last as long as 2 years, especially in patients with severe impairments. TRIAL REGISTRATION: CHA Bundang Medical Center IRB, No. 2015-06-093, approved on July 29, 2015, ( https://www.e-irb.com:3443/devlpg/nlpgS200.jsp ), ClinicalTrials.gov, NCT03130816, retrospectively registered on April 27, 2017 ( https://clinicaltrials.gov/ct2/show/NCT03130816?term=NCT03130816&draw=2&rank=1 ).

Enhancement of the Anticancer Ability of Natural Killer Cells through Allogeneic Mitochondrial Transfer.

An in vitro culture period of at least 2 weeks is required to produce sufficient natural killer (NK) cells for immunotherapy, which are the key effectors in hematological malignancy treatment. Mitochondrial damage and fragmentation reduce the NK cell immune surveillance capacity. Thus, we hypothesized that the transfer of healthy mitochondria to NK cells could enhance their anticancer effects. Allogeneic healthy mitochondria isolated from WRL-68 cells were transferred to NK cells. We evaluated NK cells' proliferative capacity, cell cycle, and cytotoxic capacity against various cancer cell types by analyzing specific lysis and the cytotoxic granules released. The relationship between the transferred allogenic mitochondrial residues and NK cell function was determined. After mitochondrial transfer, the NK cell proliferation rate was 1.2-fold higher than that of control cells. The mitochondria-treated NK cells secreted a 2.7-, 4.1-, and 5-fold higher amount of granzyme B, perforin, and IFN-γ, respectively, when co-cultured with K562 cells. The specific lysis of various solid cancer cells increased 1.3-1.6-fold. However, once allogeneic mitochondria were eliminated, the NK cell activity returned to the pre-mitochondrial transfer level. Mitochondria-enriched NK cells have the potential to be used as a novel solid cancer treatment agent, without the need for in vitro cytokine-induced culture.

Fracture Liaison Service in Korea: 2022 Position Statement of the Korean Society for Bone and Mineral Research.

Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Controlled vitamin D delivery with injectable hyaluronic acid-based hydrogel for restoration of tendinopathy.

Tendinopathy is a term used to describe tendon disorders that are marked by pain and a loss of function. Recent studies demonstrated that inflammation plays an important role throughout the broad spectrum of tendinopathy. Conventional treatments such as steroid injections, analgesics, and physical modalities simply give pain relief and do not alter the disease progression without the tendon regeneration effect. Tenocytes are responsible for maintaining the tendon matrix and understanding how they function is essential to studying new treatments for tendinopathy. Our previous study showed the protective effects of vitamin D (Vit D) on damaged tenocytes. Besides its well-known effects on bone metabolism, the non-classical action of Vit D is the pleiotropic effects on modulating immune function. In the present study, we developed a Vit D delivery system with hyaluronic acid (HA), which is one of the major components of the extracellular matrix that has anti-inflammation and wound-healing properties. A novel Vit D delivery system with cross-linked HA hydrogel (Gel) and Tween 80 (T80), Vit D@Gel/T80, could be a new regeneration technique for the treatment of tendinopathy. Vit D@Gel/T80 reduced TNF-α induced damage to human tenocytes in vitro. In an animal study, the Vit D@Gel/T80 injected group demonstrated tendon restoration features. As a result, this Vit D@Gel/T80 system might be a local injection material in the treatment for tendinopathy.

Asymmetric atrophy of the multifidus in persons with hemiplegic presentation post-stroke.

Objective: To identify the asymmetry of fatty infiltration and cross-sectional areas (CSAs) of individual paravertebral muscles in persons with hemiplegic presentation post-stroke.Methods: We retrospectively reviewed 26 patients with unilateral hemiplegia who underwent lumbar magnetic resonance imaging post-stroke. CSAs and functional CSAs (FCSAs) of individual paraspinal muscles (multifidus, erector spinae, quadratus lumborum, and psoas major) at the mid-disc level were bilaterally measured from L1-L2 to L5-S1 on T2-weighted lumbar axial images. The FCSA-to-total CSA ratio of each paraspinal muscle was also calculated. These parameters were compared between the more-affected and less-affected sides, and between the less chronic and chronic phases.Results: FCSA (p = .049) and FCSA-to-total CSA ratio (p = .044) were significantly smaller at the L5-S1 multifidus on the more-affected side than on the less-affected side in the chronic phase. Other muscles showed no meaningful changes. The erector spinae on the more-affected side and the multifidus on the less-affected side significantly increased in size in the chronic phase compared with the less chronic phase.Conclusions: Persons with hemiplegic presentation may have unilateral atrophy and fatty infiltration of the multifidus on the more-affected side during the chronic phase. The comparison between the less chronic and chronic phases suggested that the recovery pattern of the trunk muscles could differ between sides in unilateral hemiplegia: increased size of the multifidus, a tonic stabilizer, on the less-affected side and of the erector spinae, a phasic muscle, on the more-affected side. This finding could be applied to trunk rehabilitation strategies for persons post-stroke.

Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro.

Tendinopathy is a common musculoskeletal condition causing pain and dysfunction. Conventional treatment and surgical procedures for tendinopathy are insufficient; accordingly, recent research has focused on tendon-healing regenerative approaches. Tendon injuries usually occur in the hypoxic critical zone, characterized by increased oxidative stress and mitochondrial dysfunction; thus, exogenous intact mitochondria may be therapeutic. We aimed to assess whether mitochondrial transplantation could induce anti-inflammatory activity and modulate the metabolic state of a tendinopathy model. Exogenous mitochondria were successfully delivered into damaged tenocytes by centrifugation. Levels of Tenomodulin and Collagen I in damaged tenocytes were restored with reductions in nuclear factor-κB and matrix metalloproteinase 1. The dysregulation of oxidative stress and mitochondrial membrane potential was attenuated by mitochondrial transplantation. Activated mitochondrial fission markers, such as fission 1 and dynamin-related protein 1, were dose-dependently downregulated. Apoptosis signaling pathway proteins were restored to the pre-damage levels. Similar changes were observed in a collagenase injection-induced rat model of tendinopathy. Exogenous mitochondria incorporated into the Achilles tendon reduced inflammatory and fission marker levels. Notably, collagen production was restored. Our results demonstrate the therapeutic effects of direct mitochondrial transplantation in tendinopathy. These effects may be explained by alterations in anti-inflammatory and apoptotic processes via changes in mitochondrial dynamics.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell.

Background: Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell. Methods: Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell. Results: Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance. Conclusion: UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures.

OBJECTIVE: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. METHODS: Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. RESULTS: A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. CONCLUSION: This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

Peroneal neuropathy caused by an extraneural ganglion cyst in the supracondylar area of the femur: A case report.

RATIONALE: Peroneal neuropathy is the most common type of peripheral neuropathy in the lower extremities. The peroneal nerve is usually compressed at the lateral aspect of the fibular head. Compression by ganglion cysts are one of the numerous underlying etiologies for peroneal nerve neuropathy and are most frequently located around the fibular neck and proximal tibiofibular joint. To the best of our knowledge, this is the first report of an extraneural ganglion cyst located at the level of the distal thigh that resulted in compressive peroneal neuropathy. PATIENT CONCERNS: We report a case of a 56-year-old man with sudden onset of left foot drop and gait disturbance caused by an extraneural ganglion cyst located in the popliteal fossa. DIAGNOSIS: Electrodiagnosis (EDX) suggested a peroneal nerve lesion. Subsequently, diagnostic ultrasonography (USG) revealed a cystic mass located within the left side of the supracondylar area of femur. Further magnetic resonance imaging confirmed that the mass was located at the proximal of popliteal fossa. INTERVENTIONS: Surgical excision was performed using a direct posterior approach. The cystic mass was compressing the common peroneal nerve, and was carefully and completely removed ensuring that all nerve branches were protected. OUTCOMES: A histopathologic evaluation confirmed the diagnosis of a ganglion cyst. There were no postoperative complications. Two months after the surgery, follow-up USG revealed no evidence of cyst recurrence or residual lesions. Six months after the surgery, the ankle dorsiflexor motor power improved and he experienced less pain and hypoesthesia. LESSONS: Physicians should bear in mind that the peroneal neuropathy can occur because of the ganglion cyst in the distal thigh. The thorough evaluation of EDX and USG is crucial for the early diagnosis and surgical intervention, although there is no abnormal finding around the fibular neck.

Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2 × 2 factorial randomized placebo-controlled trial.

BACKGROUND: Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP. METHODS: Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 107/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored. RESULTS: Eighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration. CONCLUSIONS: These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01991145 , registered 25 November 2013.

Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists.

Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron with IC(50)s of 25, 32 and 28 nM, respectively.

Restoration of Cellular Proliferation and Characteristics of Human Tenocytes by Vitamin D.

Vitamin D (Vit D) increases calcium absorption in the intestine after binding to the Vit D receptor (VDR). The VDR has also been identified in muscle cells. Vit D supplementation resulted in improved muscle strength. However, there is a paucity of studies of the role of Vit D on tenocytes. We investigated the effects of Vit D on damaged tenocytes. Human tenocytes were treated with dexamethasone (Dex) to induce cell injury. Expression of the tenocyte-related markers tenomodulin (Tnmd), tenascin C (Tnc), scleraxis (Scx), mohawk (Mkx), and collagen (Col) 1 and 3 were measured. Then, tenocytes were cotreated with Vit D. 1-α-Hydroxylase and VDR were explored in tenocytes. With 10 µM Dex, the growth of tenocytes was significantly inhibited, and the gene expression of Tnmd, Tnc, Scx, Mkx, Col 1 and 3 also decreased. When tenocytes were cotreated with Vit D, cell proliferation recovered in a dose-dependent manner, and the expression of TNMD and Col 1 improved. When studying the mechanisms of the effects of Vit D on tenocytes, reactive oxygen species produced by Dex decreased with Vit D, and the phosphorylation of extracellular signal-regulated kinase and p38 was stimulated by Vit D cotreatment. 1-α-Hydroxylase and VDR were found in tenocytes, indicating that the cells have the ability to use an inactive form of Vit D and interact with it. Vit D is known to perform diverse actions and its protective effects on tenocytes suggest its beneficial role in tendon in addition to muscle and bone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2241-2248, 2019.