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Natural resources have recently received considerable attention as complementary or alternative hematinic agents. In this regard, olive leaf extract, which is rich in bioactive phenolic compounds, has been reported to induce erythroid differentiation in human hematopoietic stem cells. Therefore, in the present study, we aimed to explore the potential hematinic properties of aqueous olive leaf extract (WOL) in vivo. After 24 days of administering WOL to healthy mice orally, red blood cell (RBC), hematocrit, reticulocyte, and reticulocyte hemoglobin content (CHr) showed a significant increase. Additionally, WOL promoted plasma iron levels and the expression of splenic ferroportin (Fpn), an iron transporter. Additionally, a single-arm pilot study involving a limited number of healthy volunteers was conducted to assess WOL's feasibility, compliance, and potential benefits. Following an 8-week intervention with WOL, RBC count and hemoglobin level were significantly increased. Notably, there were no significant changes in the safety measures related to liver and kidney functions. Furthermore, we identified oleuropein and oleuroside as the active components in WOL to induce erythroid differentiation in the K562 cell line. Altogether, our study presents evidence of the hematinic potential of WOL in the in vivo studies, opening up exciting possibilities for future applications in preventing or treating anemia.
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Hematínicos , Olea , Humanos , Ratones , Animales , Voluntarios Sanos , Proyectos Piloto , Hierro , HemoglobinasRESUMEN
Although anterior subcutaneous pelvic internal fixation is a valuable tool for the reduction and fixation of unstable pelvic ring injuries, lateral femoral cutaneous nerve irritation by the implant is the most common complication. This study aimed to investigate the association between the nerve-to-implant distance and the postoperative lateral femoral cutaneous nerve symptom. Patients who underwent anterior subcutaneous pelvic internal fixation between 2016 and 2019 were retrospectively analyzed. Lateral femoral cutaneous nerve status was defined as follows: not identified, nerve-to-implant distance <13 mm, and ≥13 mm. The proportion of patients who experienced postoperative nerve disorders was compared using the nerve status. Nerve-to-implant distances were compared using the presence or absence of postoperative lateral femoral cutaneous nerve disorders. The predictive value of a nerve-to-implant distance of 13 mm for postoperative nerve disorders was assessed. Overall, 26 lateral femoral cutaneous nerves were included. Ten patients had postoperative nerve disorders, of which seven had an nerve-to-implant distance <13 mm, while the other three occurred in patients whose nerves were not identified. A nerve-to-implant distance ≥13 mm was significantly associated with a decreased risk of postoperative nerve disorder compared to a nerve-to-implant distance <13 mm (p = 0.017). A nerve-to-implant distance ≥13 mm had a perfect sensitivity (100%) and modest specificity (58.3%). Nerve-to-implant distance was ≥13 mm. Nerve disorders were frequently observed when the nerve-to-implant distance was <13 mm or the nerve was not identified intraoperatively. Efforts to identify the lateral femoral cutaneous nerve may be useful to avoid internal fixation-related nerve disorders.
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Fracturas Óseas , Huesos Pélvicos , Humanos , Fracturas Óseas/cirugía , Estudios Retrospectivos , Huesos Pélvicos/lesiones , Fijación Interna de Fracturas , PelvisRESUMEN
Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue infection that needs acute surgical intervention and other types of supportive care. The upper extremities are a less frequent site for this infection than the lower extremities. Axillary necrotizing fasciitis is quite rare and bears a high risk of iatrogenic neurovascular injuries. We report a severe case of a 39-year-old man with a right axillary necrotizing fasciitis caused by Streptococcus pyogenes. While dealing with important nerves and blood vessels at the initial emergency surgery, we marked and preserved them with vascular tapes. The patient underwent several surgical interventions for infection control in addition to supportive care to avoid limb loss and to survive. Intraoperatively, the locations of nerves and vessels could be easily found by checking the vessel tapes. Twelve months after the initial admission, the patient had no symptoms of nerve injuries and resumed work. With necrotizing fasciitis, the risk of an iatrogenic nerve injury exists even if limb amputation is avoided due to repeated debridement. We report that marking and preserving nerves and blood vessels with vascular tapes at the initial surgery may make the subsequent ones easier and may reduce iatrogenic neurovascular injury.
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Fascitis Necrotizante , Masculino , Humanos , Adulto , Fascitis Necrotizante/cirugía , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/etiología , Streptococcus pyogenes , Extremidad Superior , Enfermedad IatrogénicaRESUMEN
After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.
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Arritmias Cardíacas , Channelrhodopsins , Cicatriz , Fibroblastos , Miocitos Cardíacos , Animales , Ratones , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Cicatriz/patología , Cicatriz/fisiopatología , Fibroblastos/fisiología , Miocitos Cardíacos/fisiología , Channelrhodopsins/genética , Channelrhodopsins/fisiología , Optogenética , Conexina 43/genética , Conexina 43/fisiología , Técnicas de Inactivación de GenesRESUMEN
Background: Fracture-related infection (FRI) sometimes occurs with peri-prosthetic femoral fracture (PPF) treatment. Fracture-related infection often leads to multiple re-operations, possible non-union, a decreased clinical function, and long-term antibiotic treatment. In this multicenter study, we aimed to clarify the incidence of FRI, the causative organisms of wound infection, and the risk factors associated with post-operative infection for PPF. Patients and Methods: Among 197 patients diagnosed with peri-prosthetic femoral fracture who received surgical treatment in 11 institutions (named the TRON group) from 2010 to 2019, 163 patients were included as subjects. Thirty-four patients were excluded because of insufficient follow-up (less than six months) or data loss. We extracted the following risk factors for FRI: gender, body mass index, smoking history, diabetes mellitus, chronic hepatitis, rheumatoid arthritis, dialysis, history of osteoporosis treatment, injury mechanism (high- or low-energy), Vancouver type, and operative information (waiting period for surgery, operation time, amount of blood loss, and surgical procedure). We conducted a logistic regression analysis to investigate the risk factors for FRI using these extracted items as explanatory variables and the presence or absence of FRI as the response variable. Results: Fracture-related infection occurred after surgery for PPF in 12 of 163 patients (7.3%). The most common causative organism was Staphylococcus aureus (n = 7). The univariable analysis showed differences for dialysis (p = 0.001), Vancouver type (p = 0.036), blood loss during surgery (p = 0.001), and operative time (p = 0.001). The multivariable logistic-regression analysis revealed that the patient background factor of dialysis (odds ratio [OR], 22.9; p = 0.0005), and the operative factor of Vancouver type A fracture (OR, 0.039-1.18; p = 0.018-0.19) were risk factors for FRI. Conclusions: The rate of post-operative wound infection in patients with a PPF was 7.3%. Staphylococcus was the most frequent causative organism. The surgeon should pay attention to infection after surgery for patients with Vancouver type A fractures and those undergoing dialysis.
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Fracturas del Fémur , Fracturas Periprotésicas , Humanos , Estudios Retrospectivos , Incidencia , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Fracturas del Fémur/epidemiología , Fracturas del Fémur/cirugía , Fracturas del Fémur/diagnóstico , Factores de Riesgo , Infección de la Herida Quirúrgica/epidemiologíaRESUMEN
We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.
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Case: A 59-year-old man presented with posterior sternoclavicular joint dislocation concomitant with fracture-dislocations of multiple thoracic costovertebral joints caused by traumatic injury. The posterior sternoclavicular joint dislocation was treated using an ultra-high molecular weight polyethylene fiber cable and the joint was stabilized. The degree of malpositioning of the thoracic costovertebral joints was difficult to reduce. Conclusion: The patient achieved an excellent shoulder range of motion at 12 months postoperatively; however, chronic shoulder stiffness and posterior neck discomfort persisted.
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Osteoporotic acetabular fractures in elderly patients have recently been increasing, but the best treatment remains uncertain due to the difficulty in stabilizing these fractures with osteosynthesis. We performed total hip arthroplasty with an impacted bone graft on the acetabula of 3 elderly patients with comminuted acetabular fractures after confirming acetabular callus formation via radiographic imaging 2 months following the patients' initial injuries. Two of the patients presented in the subacute phase after conservative treatment, and 1 patient had no history of trauma or quadrilateral surface destruction. Two patients achieved good functional results at the 3-year follow-up. Furthermore, no loosening of the prosthesis components or subsidence of the acetabular cemented cup was evident on radiographic imaging in any of the patients.
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An extensor tendon defect in the hand requires reconstruction to restore extension. We report a 44-year-old woman with a 24-mm extensor tendon defect of the middle finger over the dorsum of the hand that was reconstructed using a composite graft consisting of the triceps tendon and paratenon. This composite graft from the posterior aspect of the distal arm is simple, safe and may be considered in extensor tendon reconstruction. Level of Evidence: Level V (Therapeutic).
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Brazo , Procedimientos de Cirugía Plástica , Femenino , Humanos , Adulto , Brazo/cirugía , Tendones/trasplante , Extremidad Superior/cirugía , Mano/cirugíaRESUMEN
BACKGROUND Peripherally inserted central catheters (PICCs) are commonly used by clinicians in daily practice as a safe and reliable alternative to central venous catheters. While there are advantages to the use of PICCs, such as a low insertion-related complication rate and cost-effectiveness, using PICCs may expose patients to life-threatening severe complications such as a central line-associated bloodstream infection and deep venous thrombosis (DVT). There have been no reports of infectious myositis associated with PICC insertion. CASE REPORT We report a case of infectious myositis related to PICC insertion complicated by brachial DVT in a 43-year-old immunocompromised patient with myelodysplastic syndrome. Despite the administration of broad-spectrum antibiotics, the patient's condition did not improve. He developed septic shock and required emergency excision of the infected and necrotic muscles. Although the pathogen responsible for the infection was unknown, infectious myositis and myonecrosis were observed intraoperatively. Furthermore, histopathological examination revealed evidence of infectious myositis in the biceps brachii and brachial muscles. The septic shock resolved with treatment and the patient survived with residual elbow joint dysfunction. CONCLUSIONS We present a case of infectious myositis related to PICC insertion. We believe that urgent resection of infected and necrotic tissues, rather than broad-spectrum antimicrobial therapy alone, was essential to save the patient's life.
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Cateterismo Venoso Central , Cateterismo Periférico , Catéteres Venosos Centrales , Miositis , Choque Séptico , Adulto , Antibacterianos , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Humanos , Masculino , Miositis/etiología , Miositis/terapia , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Choque Séptico/etiologíaRESUMEN
BACKGROUND: Muscle denervation from trauma and motor neuron disease causes disabling morbidities. A limiting step in functional recovery is the regeneration of neuromuscular junctions (NMJs) for reinnervation. Stem cells have the potential to promote these regenerative processes, but current approaches have limited success, and the optimal types of stem cells remain to be determined. Neural crest stem cells (NCSCs), as the developmental precursors of the peripheral nervous system, are uniquely advantageous, but the role of NCSCs in neuromuscular regeneration is not clear. Furthermore, a cell delivery approach that can maintain NCSC survival upon transplantation is critical. METHODS: We established a streamlined protocol to derive, isolate, and characterize functional p75+ NCSCs from human iPSCs without genome integration of reprogramming factors. To enhance survival rate upon delivery in vivo, NCSCs were centrifuged in microwell plates to form spheroids of desirable size by controlling suspension cell density. Human bone marrow mesenchymal stem cells (MSCs) were also studied for comparison. NCSC or MSC spheroids were injected into the gastrocnemius muscle with denervation injury, and the effects on NMJ formation and functional recovery were investigated. The spheroids were also co-cultured with engineered neuromuscular tissue to assess effects on NMJ formation in vitro. RESULTS: NCSCs cultured in spheroids displayed enhanced secretion of soluble factors involved in neuromuscular regeneration. Intramuscular transplantation of spheroids enabled long-term survival and retention of NCSCs, in contrast to the transplantation of single-cell suspensions. Furthermore, NCSC spheroids significantly improved functional recovery after four weeks as shown by gait analysis, electrophysiology, and the rate of NMJ innervation. MSC spheroids, on the other hand, had insignificant effect. In vitro co-culture of NCSC or MSC spheroids with engineered myotubes and motor neurons further evidenced improved innervated NMJ formation with NCSC spheroids. CONCLUSIONS: We demonstrate that stem cell type is critical for neuromuscular regeneration and that NCSCs have a distinct advantage and therapeutic potential to promote reinnervation following peripheral nerve injury. Biophysical effects of spheroidal culture, in particular, enable long-term NCSC survival following in vivo delivery. Furthermore, synthetic neuromuscular tissue, or "tissues-on-a-chip," may offer a platform to evaluate stem cells for neuromuscular regeneration.
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Células Madre Pluripotentes Inducidas , Células-Madre Neurales , Desnervación , Humanos , Cresta Neural , Neurogénesis/fisiologíaRESUMEN
Introduction: The coronoid process of the ulna is the primary stabilizer of the elbow joint. There has not yet been an accurate off-the-shelf dedicated implant because fragments of coronoid process fractures are often small and diverse. The variable angle locking compression mesh plate 2.4/2.7 (Depuy Synthes, West Chester, PA, USA) acts as a versatile, low-profile implant that can be cut to suit the specific fracture pattern and fits anatomically. Case presentations: We report two cases of Regan-Morrey type II ulnar coronoid process fractures in terrible triad elbow injuries. In both cases, persistent instability was fluoroscopically diagnosed after repair of the lateral structures. We performed osteosynthesis for the ulnar coronoid process fractures using a mesh plate, which we cut into a rhombus-like shape and used as a buttress plate. Here we report the good results obtained thereof. Conclusion: Considering our positive experience with using mesh plates, the mesh plate may be a good method of fixation for ulnar coronoid process fractures.
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BACKGROUND Chromobacterium violaceum (C. violaceum) is a gram-negative and facultative anaerobic oxidase-positive bacillus generally seen in tropical or subtropical areas (latitudes between 35°N and 35°S). C. violaceum infection is a rare but serious infection with high morbidity and mortality rates. Most clinicians practicing in non-tropical counties, such as Japan, are unfamiliar with it. CASE REPORT We report the first fatal case of a 49-year-old man infected with C. violaceum after a traffic accident in Japan (latitude 34.8°N). The patient reported brief submergence in a marshy muddy rice field after the accident. There was some evidence of soil and water contamination of the patient's skin and clothing, but he denied swallowing water or soil. There were no findings of pneumonitis or severe open wounds on admission. Until the night of the 7th day of hospitalization, his general conditions remained stable despite a persistent fever. However, he suddenly collapsed on the 8th day of hospitalization and died. C. violaceum bacteremia led to fatal sepsis on dissemination to the iliopsoas abscess, which is a rare combination for this infection. CONCLUSIONS Episodes of exposure to contaminated water or soil, especially in summer, are important predisposing factors for C. violaceum infection. Thus, it is vital to include C. violaceum infections as a differential diagnosis, since the mortality rate of C. violaceum infections is high and the cases of this infection have increased in non-tropical counties.
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Accidentes de Tránsito , Chromobacterium , Hospitalización , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
This report describes technical tools for the treatment of pediatric displaced and unstable diaphyseal forearm fractures, which are difficult to treat by manual closed reduction. During intramedullary fixation with Kirchner wires, we propose our original small distractor as an intraoperative distraction apparatus without open reduction. This apparatus is made using parts of the Ilizarov external fixator. Apart from general external fixation devices, our apparatus is adequate for the effective shortening and lateral dislocation of the fracture site. This adequacy is not only because of the three-dimensional control by ball joints but also owing to the gradual adjustment structure of the Quick adjust strut (Orthofix, Verona, Italy), which allows tight and fine stretching, thus making the distractor an effective reduction tool. Our findings show the feasibility and usefulness of our reduction technique and small distractor. Our small distractor is a useful intraoperative distraction apparatus without open reduction for pediatric displaced and unstable diaphyseal forearm fractures that cannot be treated by manual closed reduction. In this report, we describe the distractor, the closed reduction technique, and the clinical results of four representative cases.
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Fijación Intramedular de Fracturas , Fracturas Óseas , Niño , Antebrazo , Fracturas Óseas/cirugía , Humanos , Fracturas del Radio/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Fracturas del Cúbito/cirugíaRESUMEN
CASE PRESENTATION: A five-year-old boy presented to our emergency department with severe posterior neck pain that was exacerbated upon neck movement. Cervical spine radiography revealed calcification in the cervical intervertebral disk 3-4. DISCUSSION: Pediatric idiopathic intervertebral disk calcification is a benign, rare condition that might be complicated by associated severe neurological symptoms. In this case, the symptoms gradually subsided with conservative management alone.
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CASE PRESENTATION: A 14-year-old boy presented to the emergency department complaining of severe groin pain on the right side following a minor fall. Computed tomography and magnetic resonance imaging revealed a hematoma in his right iliacus muscle. He was diagnosed with a traumatic iliacus hematoma, and he recovered spontaneously with short-term oral analgesics. DISCUSSION: Traumatic iliacus hematomas are rare entities and subside with conservative management in most cases. However, this condition may be associated with femoral nerve palsy, and surgery is indicated in severe cases. Traumatic iliacus hematoma should be considered in the differential diagnosis of severe groin pain.
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Luxaciones Articulares/diagnóstico por imagen , Articulación Metacarpofalángica/diagnóstico por imagen , Traumatismos de los Dedos/diagnóstico por imagen , Traumatismos de los Dedos/cirugía , Humanos , Luxaciones Articulares/cirugía , Masculino , Articulación Metacarpofalángica/cirugía , Persona de Mediana Edad , Dolor/etiología , RadiografíaRESUMEN
Anaemia is one of the leading causes of disability in young adults and is associated with increased morbidity and mortality in elderly. With a global target to reduce the disease burden of anaemia, recent researches focus on novel compounds with the ability to induce erythropoiesis and regulate iron homeostasis. We aimed to explore the biological events and potential polypharmacological effects of water-extracted olive leaf (WOL) on human bone marrow-derived haematopoietic stem cells (hHSCs) using a comprehensive gene expression analysis. HPLC analysis identifies six bioactive polyphenols in the WOL. Treatment with WOL for 12 days regulated gene expressions related to erythroid differentiation, oxygen homeostasis, iron homeostasis, haem metabolism and Hb biosynthesis in hHSCs. Functional clustering analysis reveals several major functions of WOL such as ribosomal biogenesis and mitochondrial translation machinery, glycolytic process, ATP biosynthesis and immune response. Additionally, the colonies of both primitive and mature erythroid progenitors, CFU-E and BFU-E, were significantly increased in WOL-treated hHSCs. The expressions of erythroid markers, CD47, glycophorin A (GYPA), and transferrin receptor (TFRC) and adult Hb subunits-HBA and HBB were also confirmed in immunofluorescent staining and flow cytometer analysis in WOL-treated hHSCs. It is well known that induction of lineage-specific differentiation, as well as the maturation of early haematopoietic precursors into fully mature erythrocytes, involves multiple simultaneous biological events and complex signalling networks. In this regard, our genome-wide transcriptome profiling with microarray study on WOL-treated hHSCs provides general insights into the multitarget prophylactic and/or therapeutic potential of WOL in anaemia and other haematological disorders.