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BACKGROUND AND AIMS: Vulnerable plaques are closely related to ischemic stroke. To investigate the diagnostic value of multimodal plaque vulnerability ultrasound scoring system (PV-USS) using histopathology as the gold standard. METHODS: A total of 45 subjects who would be underwent carotid endarterectomy were recruited. The postoperative specimens were examined by histopathology. All responsible plaques were scanned dynamically in multiple sections by carotid ultrasound to measure maximum thickness and lumen stenotic degree, as well as, the echo, homogeneity, surface morphology, and echo type were observed. The above two-dimensional (2D) ultrasonic features were systematically scored, that is, PV-USS2D . Combined with contrast-enhanced ultrasonography (CEUS), neovascularization grade in plaque was scored, which is PV-USS2D+CEUS . RESULTS: According to the pathological results, 45 subjects were divided into vulnerable plaque group (27 cases, 60%) and non-vulnerable plaque group (18 cases, 40%). PV-USS2D and PV-USS2D+CEUS in vulnerable plaque group were higher than those in non-vulnerable plaque group (PV-USS2D : 9.44 ± 2.10 vs 7.22 ± 1.73; PV-USS2D+CEUS: 12.37 ± 2.10 vs 8.28 ± 1.81, P < .001). ROC curve analysis showed that the AUC of PV-USS2D and PV-USSCEUS was 0.783 and 0.929, respectively (P < .001). The best cutoff values of PV-USS2D and PV-USS2D+CEUS were, respectively, 9.5 (the maximum Youden index was 0.425, the sensitivity was 48.1%, the specificity was 94.4%) and 10.5 (the maximum Youden index was 0.667, the sensitivity was 77.8%, the specificity was 88.9%). CONCLUSIONS: Ultrasound scoring system may be used as an effective method to evaluate the vulnerability of plaque. The diagnostic efficiency of PV-USS2D+CEUS is more higher than PV-USS2D .
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Arterias Carótidas , Endarterectomía Carotidea , Ultrasonografía de las Arterias Carótidas , Humanos , Endarterectomía Carotidea/efectos adversos , Placa Aterosclerótica/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Estudios Prospectivos , Masculino , FemeninoRESUMEN
PURPOSE: Cases of allergy to large surgical implants have been reported. However, few studies have reported allergy to small titanium-containing implants (e.g. Zero-P device). METHODS: We reported the case of a 51-year old male patient who underwent the anterior cervical discectomy and fusion (ACDF) procedure using a Zero-P device and exhibited allergic symptoms 1 month after the surgery. RESULTS: The allergic symptoms included intermittent tingling and itches in the throat induced by speaking. Systemic rashes over the skin surface and congestion of the eyeball, and dysphagia were also present. Anti-allergic treatment did not resolve the symptoms. Patch tests revealed negative reactions to the rested reagents including titanium. Radiographic results showed solid bone fusion and no signs of chronic inflammation or hypotoxic infection in the surrounding tissues. Upon the patient's request, we removed the titanium screws and plate of the Zero-P device. No allergic reactions were observed after the surgery and at a 6-month follow-up. CONCLUSIONS: Even with a small implant such as the Zero-P device, allergy to titanium may still occur. This case demonstrated the need to screen for the presence of allergy to metals including titanium before the surgery.
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Hipersensibilidad , Fusión Vertebral , Masculino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Titanio/efectos adversos , Prótesis e Implantes , Hipersensibilidad/etiología , Hipersensibilidad/cirugía , Discectomía/efectos adversos , Discectomía/métodos , Fusión Vertebral/métodos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugíaRESUMEN
BACKGROUND: Oblique lumbar interbody fusion (OLIF) surgery has been performed as a minimally invasive lateral lumbar fusion technique in recent years. Reports of operative complications of OLIF are limited, and there are fewer reports of ureteral injuries. CASE PRESENTATION: A 62-year-old Chinese woman diagnosed with "lumbar spondylolisthesis (L4 forward slip, I degree)" underwent OLIF treatment. The surgical decompression process was smooth, and the cage was successfully placed. After the expansion sleeve of OLIF was removed, clear liquid continuous outflow from the peritoneum was found. The patient was diagnosed with a ureteral injury. The urological surgeon expanded the original incision, and left ureteral injury anastomosis and ureteral stent implantation were performed. The patient was changed to the prone position and a percutaneous pedicle screw was placed in the corresponding vertebral body. The patient was indwelled with a catheter for 2 weeks, and regular oral administration of levofloxacin to prevent urinary tract infection. After 2 months, the double J tube was removed using a cystoscope. One year after surgery, the symptoms of lumbar back were significantly improved, and there were no urinary system symptoms. However, the patient needed an annual left ureter and kidney B-ultrasound. CONCLUSION: Ureteral injury is a rare complication and is easily missed in OLIF surgery. If the diagnosis is missed, the consequences can be serious. Patients should undergo catheterization before the operation and hematuria should be observed during the operation. We emphasize the careful use of surgical instruments to prevent intraoperative complications. In addition, after withdrawing the leaf in the operation, it is necessary to carefully observe whether a clear liquid continues to leak. If ureteral injury is found, one-stage ureteral injury repair operation should be performed to prevent ureteral stricture.
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Fusión Vertebral , Espondilolistesis , Uréter , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Vértebras Lumbares/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Espondilolistesis/complicaciones , Espondilolistesis/cirugía , Resultado del Tratamiento , Uréter/cirugíaRESUMEN
BACKGROUND: Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated. METHODS: The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis. RESULTS: The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells. CONCLUSIONS: In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma.
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OBJECTIVE: The aim of this study was to evaluate the sonographic features and to compare the sonographic findings with the pathologic features. METHODS: The sonographic and pathological features of all patients were retrospectively reviewed. RESULTS: All these 9 patients presented with a palpable breast mass first found by the patient before presentation. The median diameters were 3.67 cm. On two-dimensional imaging, 8 masses showed mixed echogenicity with both solid and cystic components, and only 1 mass showed hypoechoic. All the masses had irregular shapes. 1 mass had indistinct margin and 8 masses had microlobulated margins. Calcifications was seen in 1 mass. On color Doppler flow imaging, 8 masses had high vascularity with high resistance index; 5 masses had grade III blood flow signal; 3 masses had grade II blood flow signal. On histopathological examination, 5 masses were adenocarcinoma with squamous metaplasia, and 4 masses were pure SCC. On immunohistochemical staining, estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER2) were negative in 5 masses. There were 2 patients with lymph node metastasis. CONCLUSIONS: Most of the sonographic features of MSCC were mixed echogenicity with central cystic components, posterior echo enhancement, abundant vascularity with high resistance.
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Neoplasias de la Mama , Carcinoma de Células Escamosas , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Femenino , Humanos , Metástasis Linfática , Estudios Retrospectivos , UltrasonografíaRESUMEN
BACKGROUND: There is no available literature for comparison on muscle atrophy between the "stand-alone" oblique lateral interbody fusion (OLIF) and regular OLIF (i.e., combined with percutaneous pedicle screws fixation (PPSF) in patients with spondylolisthesis). This study aimed to identify changes in back muscle atrophy between the two surgeries. METHODS: This was a retrospective cohort study of patients who underwent OLIF or OLIF+PPSF at Beijing Jishuitan Hospital and Shanghai ChangZheng Hospital between 07/2014 and 10/2017. Computed tomography (CT) was used to measure functional cross-sectional area (FCSA) and fat infiltration percentage (FIP) of the multifidus and erector spinae before and 24 months after surgery. RESULT: There were no differences in FCSA and FIP between OLIF (n = 32) and OLIF+PPSF (n = 41) groups before surgery. In the OLIF group, the multifidus and erector spinae FCSA and FIP did not change at 24 months (FCSA: multifidus: from 8.59 ± 1.76 to 9.39 ± 1.74 cm2, P = 0.072; erector spinae: from 13.32 ± 1.59 to 13.55 ± 1.31 cm2, P = 0.533) (FIP: multifidus: from 15.91 ± 5.30% to 14.38 ± 3.21%, P = 0.721; erector spinae: from 11.63 ± 3.05% to 11.22 ± 3.12%, P = 0.578). In the OLIF+PPSF group, the multifidus and erector spinae FCSA decreased (multifidus: from 7.72 ± 2.69 to 5.67 ± 1.71 cm2, P < 0.001; erector spinae: from 12.60 ± 2.04 to 10.15 ± 1.82 cm2, P < 0.001), while the FIP increased (multifidus: from 16.13 ± 7.01% to 49.38 ± 20.54%, P < 0.001; erector spinae: from 11.93 ± 3.22% to 22.60 ± 4.99%, P < 0.001). The differences of FCSA and FIP between the two groups at 24 months were significant (all P < 0.001). The patients in the standalone OLIF group had better VAS back pain, and JOA scores than the patients in the OLIF combined group (all P < 0.05) at 1 week and 3 months after surgery. There were two cases (4.9%) of adjacent segment degeneration in the OLIF combined group, while there was no case in the OLIF alone group. CONCLUSIONS: Standalone OLIF had better clinical outcomes at 1 week and 3 months than OLIF+PPSF in patients with spondylolisthesis. OLIF may not result in paraspinal muscle atrophy at 24 months after surgery.
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Fijadores Internos , Complicaciones Intraoperatorias/etiología , Vértebras Lumbares/cirugía , Atrofia Muscular/etiología , Músculos Paraespinales/patología , Tornillos Pediculares , Fusión Vertebral/métodos , Espondilolistesis/cirugía , Tejido Adiposo/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Intraoperatorias/patología , Dolor de la Región Lumbar/etiología , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Atrofia Muscular/patología , Osteoporosis/complicaciones , Músculos Paraespinales/lesiones , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Fusión Vertebral/instrumentación , Espondilolistesis/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: To compare standalone oblique lateral interbody fusion (OLIF) vs. OLIF combined with posterior bilateral percutaneous pedicle screw fixation (OLIF combined) for the treatment of lumbar spondylolisthesis. METHODS: This was a retrospective study of patients who underwent standalone OLIF or combined OLIF between 07/2014 and 08/2017 at two hospitals in China. Direct decompressions were not performed. Visual analog scale (VAS), Oswestry Disability Index (ODI), satisfaction rate, anterior/posterior disc heights (DH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, fusion rate, and complications were analyzed. All imaging examinations were read independently by two physicians and the mean measurements were used for analysis. RESULTS: A total of 73 patients were included: 32 with standalone OLIF and 41 with combined OLIF. The total complication rate was 25.0% with standalone OLIF and 26.8% with combined OLIF. There were no differences in VAS and ODI scores by 2 years of follow-up, but the scores were better with standalone OLIF at 1 week and 3 months (P < 0.05). PDH and FW was smaller in the combined OLIF group compared with the standalone OLIF group before and after surgery (all P < 0.05). There were significant differences in FH before surgery and at 1 week and 3 months between the two groups (all P < 0.05), but the difference disappeared by 2 years (P = 0.111). Cage subsidence occurred in 7.3% (3/41) and 7.3% (3/41) of the patients at 3 and 24 months, respectively, in the combined OLIF group, compared with 6.3% (2/32) and 15.6% (5/32), respectively, in the standalone OLIF group at the same time points (P = 0.287). There was no cage retropulsion in both groups at 2 years. The fusion rate was 85.4%(35/41) in the combined OLIF group and 84.4% (27/32) in the standalone OLIF group at 3 months(P = 0.669). At 24 months, the fusion rate was 100.0% in the combined OLIF group and 93.8% (30/32) in the standalone OLIF group (P = 0.066). CONCLUSION: Standalone OLIF may achieve equivalent clinical and radiological outcomes than OLIF combined with fixation for spondylolisthesis. The rate of complications was similar between the two groups. Patients who are osteoporotic might be better undergoing combined rather than standalone OLIF. The possibilty of proof lies within a future prospective study, preferably an RCT.
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Fijadores Internos , Complicaciones Intraoperatorias/etiología , Vértebras Lumbares/cirugía , Tornillos Pediculares , Fusión Vertebral/métodos , Espondilolistesis/cirugía , Anciano , China , Femenino , Humanos , Complicaciones Intraoperatorias/patología , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Músculos Paraespinales/lesiones , Músculos Paraespinales/patología , Radiografía , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Fusión Vertebral/instrumentación , Espondilolistesis/complicacionesRESUMEN
Objective: To evaluate the clinical efficacy, practicability, and safety of an ultrasonic osteotome for percutaneous transforaminal endoscopic discectomy (PTED) in patients with calcified lumbar disc herniation (CLDH).Methods: A total of 25 CLDH patients who underwent PTED at our department between December 2017 and August 2018 were analyzed retrospectively. Post-operative lumbar spine CT was used to evaluate residual calcification. Efficacy was evaluated by pre- and post-operative with the pain visual analog scale (VAS), Oswestry disability index (ODI), and the Modified MacNab Scale; the incidence of intra- and postoperative complications was also analyzed.Results: All procedures were successfully completed and none of the patients was lost to follow-up. Postoperative CT verified the successful removal of calcified protrusions. VAS and ODI scores improved significantly after surgery. Based on the Modified MacNab scale, >90% patients achieved good or excellent outcomes. There were no complications such as dural tear and infection. Seven patients had varying degrees of postoperative dysesthesia. One patient experienced recurrence of herniation within 1 week after operation; successful recovery was achieved after repeat PTED.Conclusions: Use of this ultrasonic osteotome for PTED facilitated effective removal of calcified disc protrusion, relieved nerve compression, and protected the adjacent neurovascular tissues. The instrument may help expand the indications for endoscopic surgery and avoid open surgery for some CLDH patients.
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Calcinosis/cirugía , Discectomía Percutánea/métodos , Endoscopía/métodos , Endosonografía/métodos , Desplazamiento del Disco Intervertebral/cirugía , Procedimientos Neuroquirúrgicos/métodos , Adulto , Calcinosis/diagnóstico por imagen , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Complicaciones Intraoperatorias/epidemiología , Masculino , Dimensión del Dolor , Dolor Postoperatorio/epidemiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the methodology for the establishment of the urethral stricture model in rats, the methods of end-point imaging evaluation of the model establishment and their efficiency. METHODS: Twenty-four adult male rats were randomly divided into a blank control (n = 6) and a model group (n = 18), and the model was established by cutting the penile segment of the urethra to induce incomplete urethral rupture. Then the model rats were treated by injection of transforming growth factor-ß1 (the TGF group, n = 6) or mesenchymal stem cells (the MSC group, n = 12) into the urethral cavernosum. At 4 weeks after modeling, the urethral condition of all the rats was evaluated blindly using high-frequency ultrasound combined with water bath, followed by comparison among different groups. RESULTS: Compared with the blank controls, the model rats showed evident urethral stricture, with more significant urethral fibrous tissue hyperplasia in the TGF than in the MSC group. Ultrasonography revealed significantly narrowed echo strips (P < 0.01), decreased echo intensity and blurred echoes in some strips. The grouping of the model rats according to the assigned values to the ultrasonographic changes was consistent with the actual condition. The area under the ROC curve for distinguishing between the TGF and MSC groups was 0.972, with a sensitivity of 100.0% and a specificity of 83.3% when ultrasound assignment score was 7.5. CONCLUSIONS: High-frequency ultrasonography combined with water bath is effective for evaluating urethral stricture in rats and may give some guidance in the establishment of the urethral stricture model.
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Uretra/diagnóstico por imagen , Estrechez Uretral , Animales , Masculino , Trasplante de Células Madre Mesenquimatosas , Ratas , Factor de Crecimiento Transformador beta1/administración & dosificación , Ultrasonografía , Uretra/patología , Estrechez Uretral/diagnóstico por imagenRESUMEN
The effective treatment of urethral stricture remains a medical problem. The use of proinflammatory cytokines as stimuli to improve the reparative efficacy of mesenchymal stem cells (MSCs) towards damaged tissues represents an evolving field of investigation. However, the therapeutic benefits of this strategy in the treatment of urethral stricture remain unknown. Here, we enriched exosomes derived from human umbilical cord-derived MSCs pretreated with or without tumor necrosis factor alpha (TNF-α) to evaluate their therapeutic effects in an in vivo model of TGFß1-induced urethral stricture. Male Sprague-Dawley rats received sham (saline) or TGFß1 injections to urethral tissues followed by incisions in the urethra. Animals in the TGFß1 injection (urethral fibrosis) cohort were subsequently injected with vehicle control, or with exosomes derived from MSCs cultured with or without TNF-α. After 4 weeks, rats underwent ultrasound evaluation and, following euthanasia, urethral tissues were harvested for histological and molecular analysis. In vitro, the effects of MSC-derived exosomes on fibroblast secretion of collagen and cytokines were studied by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. Exosomes derived from MSCs pretreated with TNF-α were more effective in suppressing urethral fibrosis and stricture than exosomes from untreated MSCs. We found that miR-146a, an anti-inflammatory miRNA, was strongly upregulated in TNF-α-stimulated MSCs and was selectively packaged into exosomes. Moreover, miR-146a-containing exosomes were taken up by fibroblasts and inhibited fibroblast activation and associated inflammatory responses, a finding that may underlie the therapeutic mechanism for suppression of urethral stricture. Inhibition of miR-146a in TNF-α-treated MSCs partially reduced antifibrotic effects and increased the release of proinflammatory factors of exosomes derived from these cells. Together these findings demonstrate that exosomes derived from TNF-α-treated MSCs are of therapeutic benefit in urethral fibrosis, suggesting that this strategy may have utility as an adjuvant therapy in the treatment of urethral stricture diseases.
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Exosomas/trasplante , MicroARNs/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Estrechez Uretral/patología , Animales , Exosomas/metabolismo , Fibroblastos/metabolismo , Fibrosis , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Discography can increase disc degeneration, but the influence of different discography variables on the degeneration of discs has not been reported. The aim of this study was to investigate the effects of discography variables of needle diameter, type of contrast agent and volume of contrast agent on disc degeneration. METHODS: Three separate experiments examined needle diameter, and type and volume of contrast agent. Coccygeal discs (Co7-10) adult male rats were used. X-rays were used to detect the disc height degeneration index at 1, 2 and 4 weeks after the procedure. MRI was used to study the changes in the disc structure and the signal intensity of IVD 2 and 4 weeks after the procedure. Disc water content and histology were measured at 4 weeks after the procedure. RESULTS: A 21-g needle significantly increased disc degeneration when compared with the 30-g needle as detected by X-ray, MRI, disc water content and histology (P < 0.05). Two microlitres of iodine significantly decreased the disc MRI signal and water content at 4 weeks compared with the same volume of normal saline (P < 0.05). Three microlitres of iodine significantly increased disc degeneration when compared with 2 µl iodine, as detected by X-ray, MRI, disc water content and histology at 4 weeks (P < 0.05). CONCLUSION: To reduce disc degeneration after discography, it may be best to choose a smaller needle size, minimize the use of contrast agent and use non-ionic contrast agents with osmotic pressure similar to the intervertebral disc. These slides can be retrieved under Electronic Supplementary Material.
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Medios de Contraste , Técnicas de Diagnóstico Neurológico , Degeneración del Disco Intervertebral , Disco Intervertebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Animales , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Técnicas de Diagnóstico Neurológico/efectos adversos , Técnicas de Diagnóstico Neurológico/instrumentación , Degeneración del Disco Intervertebral/diagnóstico , Degeneración del Disco Intervertebral/etiología , Masculino , Agujas/efectos adversos , RatasRESUMEN
OBJECTIVES: To discuss Doppler ultrasonographic and clinical features of middle aortic syndrome (MAS). MATERIALS AND METHODS: Doppler ultrasonographic images and clinical dates of 11 patients with MAS confirmed by angiography were retrospectively analyzed from January 2004 to September 2016. RESULTS: The median age of 11 patients was 10 years (1-39 years). Ten patients presented with hypertension, only 2 cases presented with symptomatic intermittent claudication, and 1 case presented with abdominal pain. The ultrasonographic features of 11 patients with MAS included: (a) Gray-scale image showed significant segmental narrowing of the aorta in 9 cases. (b) Color Doppler demonstrated aliasing in the suspicious narrowed vessels of all cases. (c) On Spectral Doppler image, peak systolic velocity in the location of aorta coarctation was significantly elevated (range, 2.3~4.8 m/s). When infrarenal aorta was involved, a tardus-parvus waveform was only seen in the distal aorta. When suprarenal or inter-renal aorta was involved, a tardus-parvus pattern was seen in the distal aorta as well as renal artery. CONCLUSIONS: Significant segmental narrowing and a tardus-parvus waveform are the important ultrasonographic features in patients with MAS, the latter may be more reliable. Doppler ultrasound can be used as a simple screening method, especially for children and adolescents suspected of having a vascular cause of refractory hypertension.
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Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/fisiopatología , Ultrasonografía Doppler/métodos , Adolescente , Adulto , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/fisiopatología , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Síndrome , Adulto JovenRESUMEN
BACKGROUND/AIMS: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1ß, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1ß. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1ß mediated NP cell degeneration and apoptosis. METHODS: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1ß (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1ß for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. RESULTS: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1ß induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1ß induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1ß. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1ß, this function was blocked by autophagy inhibitor, 3-methyladenine. CONCLUSION: APO866 protects NP cells and induces autophagy by inhibiting IL-1ß-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.
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Acrilamidas/farmacología , Autofagia/efectos de los fármacos , Interleucina-1beta/farmacología , Degeneración del Disco Intervertebral/patología , Nicotinamida Fosforribosiltransferasa/metabolismo , Piperidinas/farmacología , Proteína ADAMTS4/metabolismo , Agrecanos/metabolismo , Células Cultivadas , Colágeno Tipo II/metabolismo , Citocinas/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Humanos , Degeneración del Disco Intervertebral/metabolismo , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Nicotinamida Fosforribosiltransferasa/genética , Núcleo Pulposo/citología , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismoRESUMEN
Spinal disk herniation can induce radicular pain through chemical irritation caused by proinflammatory and immune responses. Bone marrow mesenchymal stem cells (BMSCs) are a unique type of adult stem cell with the functions of suppressing inflammation and modulating immune responses. This study was undertaken to observe the effect of intrathecal BMSCs on the treatment of mechanical allodynia and the suppression of microglial activation in a rat noncompressive disk herniation model. The model was induced by the application of nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). The study found that the use of NP in the DRG can induce abnormal mechanical pain, increase the contents of the proinflammatory factors TNF-α and IL-1ß, decrease the content of the anti-inflammatory cytokine TGF-ß1 and activate microglia in the spinal dorsal horns (L5) (P < 0.05). BMSC administration could increase the mechanical withdrawal thresholds dramatically, decrease the contents of IL-1ß and TNF-α, increase the content of TGF-ß1 significantly (P < 0.05) and inhibit microglial activation in the bilateral spinal dorsal horn. Our results indicate that BMSC administration can reduce mechanical allodynia and downregulate the expression of proinflammatory cytokines by inhibiting microglial activation in the spinal dorsal horn in a rat noncompressive disk herniation model.
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Degeneración del Disco Intervertebral/terapia , Desplazamiento del Disco Intervertebral/terapia , Células Madre Mesenquimatosas/metabolismo , Microglía/metabolismo , Animales , Degeneración del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral/patología , Masculino , Células Madre Mesenquimatosas/citología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The aim of this study was to determine whether internal or external drainage with a pancreatic duct stent is the optimal pancreaticojejunostomy method to prevent pancreatic fistula (PF) after pancreaticoduodenectomy (PD) for subgroups of patients at high risk for PF. MATERIALS AND METHODS: A total of 495 patients who underwent PD were reviewed. Univariate and multivariate analyses were used to identify risk factors for PF after PD. We further compared the incidence of PF and outcomes between the internal and external drainage groups for subgroups of patients at high risk for PF. RESULTS: There was no difference in the incidence of complications according to the Clavien-Dindo classification or the rate of PF after PD in both groups (P = 0.961 and P = 0.505, respectively). The incidence of mortality was 3.8% in the internal drainage group and 3.9% in the external drainage group (P = 0.980). Univariate and multivariate analyses identified male gender (odds ratio [OR] = 2.93; 95% confidence interval [CI], 1.78-4.83; P = 0.000), pancreatic duct diameter (<3 mm) (OR = 2.58; 95% CI, 1.57-4.23; P = 0.000), and soft pancreatic texture (OR = 2.92; 95% CI, 1.71-4.98; P = 0.000) as independent risk factors for PF after PD. No differences in the incidence of PF for the subgroups of patients with one, two, or three risk factors were observed between the internal and external drainage groups (P = 0.334, P = 1.000, and P = 0.936, respectively). No differences in total complications, delayed gastric emptying, postpancreatectomy hemorrhage, biliary fistula, infection complications, reoperation, perioperative mortality, or postoperative hospital stay were noted. In addition, liquid loss and tube-related complications occurred in the external drainage group. CONCLUSIONS: Internal drainage is the optimal method to prevent PF after PD for subgroups of patients at high risk for PF because the surgical procedure is simple and prevents liquid loss and tube-related complications associated with external drainage. However, no differences in the incidence of PF and other complications after PD were observed between the two approaches.
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Drenaje/métodos , Conductos Pancreáticos , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/métodos , Pancreatoyeyunostomía/métodos , Stents , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/prevención & control , Factores de RiesgoRESUMEN
This study aims to fabricate and deposit nanoscale multilayers on polyetheretherketone (PEEK) to improve cell adhesion and osseointegration. Bio-activated PEEK constructs were designed with prepared surface of different layers of polystyrene sulfonate (PSS) and polyallylamine hydrochloride (PAH) multilayers. Irregular morphology was found on the 5 and 10-layer PEEK surfaces, while "island-like" clusters were observed for 20-layer (20 L) multilayers. Besides, the 20 L PEEK showed more hydrophilic feature than native PEEK, and the surface contact angle reduced from 39.7° to 21.7° as layers increased from 5 to 20. In vitro, modified PEEK allowed excellent adhesion and proliferation of bone marrow stromal cells, and induced higher cell growth rate and alkaline phosphatase level. In vivo, this bio-active PEEK exhibited significantly enhanced integration with bone tissue in an osteoporosis rabbit model. This work highlights layer-by-layer self-assembly as a practical method to construct bio-active PEEK implants for enhanced osseointegration.
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Cetonas/química , Células Madre Mesenquimatosas/efectos de los fármacos , Oseointegración , Osteoporosis/tratamiento farmacológico , Polietilenglicoles/química , Prótesis e Implantes , Animales , Benzofenonas , Materiales Biocompatibles/química , Adhesión Celular , Células Cultivadas , Femenino , Células Madre Mesenquimatosas/citología , Polímeros , Conejos , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Lateral lumbar interbody fusion (LLIF) is a popular, minimally invasive technique that is used to address challenging multilevel degenerative spinal diseases. It remains controversial whether supplemental instrumentation should be added for multilevel LLIF. In this study, we compared the kinematic stability afforded by stand-alone lateral cages with those supplemented by bilateral pedicle screws and rods (PSR), unilateral PSR, or lateral plate (LP) fixation using a finite-element (FE) model of a multi-level LLIF construct with simulated osteoporosis. Additionally, to evaluate the prospect of cage subsidence, the stress change characteristics were surveyed at cage-endplate interfaces. METHODS: A nonlinear 3-dimensional FE model of the lumbar spine (L2 to sacrum) was used. After validation, four patterns of instrumented 3-level LLIF (L2-L5) were constructed for this analysis: (a) 3 stand-alone lateral cages (SLC), (b) 3 lateral cages with lateral plate and two screws (parallel to endplate) fixated separately (LPC), (c) 3 lateral cages with bilateral pedicle screw and rod fixation (LC + BPSR), and (d) 3 lateral cages with unilateral pedicle and rod fixation (LC + UPSR). The segmental and overall range of motion (ROM) of each implanted condition were investigated and compared with the intact model. The peak von Mises stresses upon each (superior) endplate and the stress distribution were used for analysis. RESULTS: BPSR provided the maximum reduction of ROM among the configurations at every plane of motion (66.7-90.9% of intact spine). UPSR also provided significant segmental ROM reduction (45.0-88.3%). SLC provided a minimal restriction of ROM (10.0-75.1%), and LPC was found to be less stable than both posterior fixation (23.9-86.2%) constructs. The construct with stand-alone lateral cages generated greater endplate stresses than did any of the other multilevel LLIF models. For the L3, L4 and L5 endplates, peak endplate stresses caused by the SLC construct exceeded the BPSR group by 52.7, 63.8, and 54.2% in flexion, 22.3, 40.1, and 31.4% in extension, 170.2, 175.1, and 134.0% in lateral bending, and 90.7, 45.5, and 30.0% in axial rotation, respectively. The stresses tended to be more concentrated at the periphery of the endplates. CONCLUSIONS: SLC and LPC provided inadequate ROM restriction for the multilevel LLIF constructs, whereas lateral cages with BPSR or UPSR fixation provided favorable biomechanical stability. Moreover, SLC generated significantly higher endplate stress compared with supplemental instrumentation, which may have increased the risk of cage subsidence. Further biomechanical and clinical studies are required to validate our FEA findings.
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Vértebras Lumbares/cirugía , Región Lumbosacra/cirugía , Osteoporosis/cirugía , Rango del Movimiento Articular , Fusión Vertebral/instrumentación , Fenómenos Biomecánicos , Placas Óseas , Cadáver , Análisis de Elementos Finitos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiología , Región Lumbosacra/diagnóstico por imagen , Región Lumbosacra/fisiología , Masculino , Tornillos Pediculares , Fusión Vertebral/métodos , Tomografía Computarizada por Rayos XRESUMEN
A suitable drug-loaded scaffold that can postoperatively release an antituberculosis drug efficiently in a lesion area and help repair a bone defect is very important in the clinical treatment of bone tuberculosis (TB). In this study, a composite drug-loaded cylindrical scaffold was prepared by using three-dimensional printing technology in combination with the mesoporous confinement range, surface chemical groups, and gradual degradation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). This achieves the slow release of a drug for as long as possible. We implanted the drug-loaded compound scaffold into New Zealand rabbits' femur defect model to study the in vivo drug release performance and osteogenic ability. The in vivo release of isoniazid and rifampicin from the prepared composites could be effectively sustained for 12 weeks in local tissues, whereas these drugs were sustained for just 2 weeks in a control group. The blood drug concentrations were very low and most concentrations were below 5 µg/ml. Therefore, the systemic toxic adverse effect is very low. In addition, the composite exhibits good osteogenic potential in a rabbit bone defect model. The results of this study indicate that this composite has great potential for treating osteoarticular TB.
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Antituberculosos/administración & dosificación , Implantes de Medicamentos/química , Fracturas del Fémur/terapia , Regeneración Tisular Dirigida/instrumentación , Andamios del Tejido , Tuberculosis Osteoarticular/tratamiento farmacológico , Ácido 3-Hidroxibutírico/química , Animales , Antituberculosos/química , Regeneración Ósea/efectos de los fármacos , Caproatos/química , Terapia Combinada/instrumentación , Terapia Combinada/métodos , Implantes de Medicamentos/administración & dosificación , Análisis de Falla de Equipo , Vidrio/química , Osteogénesis/efectos de los fármacos , Impresión Tridimensional , Diseño de Prótesis , Conejos , Resultado del TratamientoRESUMEN
OBJECTIVE: To establish the three dimensional finite element model of bilateral cervical articular process locking and verify its effectiveness. METHODS: A healthy adult male underwent cervical thin-layer computed tomography (CT) scan. The software programs of Simpleware3.0, Geomagic8.0, Hypermesh9.0, Abaqus6.9 and Rhino4.0 were employed to establish a complete C4, C5 segment (including intervertebral disc and ligament tissue) finite element model. A spring force load of 180 n was applied along the direction of cervical curvature. The locking of articular process was simulated. And its effectiveness was compared with previous experiments. RESULTS: Detailed anatomy structure of cervical spine was established. Simulated bilateral joints in journey finally formed. The load-displacement situations and experiment results of small joint ligament were consistent. And shear forces and displacement differences of modeling was insignificant. CONCLUSION: The three dimensional finite element model of bilateral cervical articular process locking has excellent biological fidelity. And it is suitable for clinical applications.
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Vértebras Cervicales/anatomía & histología , Análisis de Elementos Finitos , Disco Intervertebral/anatomía & histología , Articulación Cigapofisaria/anatomía & histología , Adulto , Humanos , Imagenología Tridimensional , Masculino , Modelos Anatómicos , Rango del Movimiento ArticularRESUMEN
OBJECTIVE: To evaluate the mid-term clinical outcomes of unilateral pedicle screw fixation with lumbar interbody fusion for lumber degenerative diseases. METHODS: From October 2008 to December 2010, unilateral pedicle screw fixation with lumbar interbody fusion was performed for a consecutive cohort of 42 patients. There were 18 males and 24 females with an average age of 52 (38-69) years. The operation level at L3-4 (n = 2), L4-5 (n = 19), L5-S1 (n = 21) and multilevel (n = 0). Their clinical outcomes were assessed by Oswestry (ODI) scores and Japanese Orthopedics Association (JOA) questionnaires before and after operation. Operative duration, intraoperative blood loss, incision status and complications were recorded. Radiological examination was performed to assess the height of intervertebral space, the postoperative intervertebrai fusion conditions and the degeneration of adjacent segments. RESULTS: The mean operative duration was 90 minutes and mean blood loss 150 ml. All incisions healed primarily. The mean follow-up period was 40 (36-58) months. The ODI scores decreased significantly from 59.1 ± 9.6 preoperatively to 8.5 ± 2.7 postoperatively (P < 0.05). The JOA scores improved markedly from 8.3 ± 2.7 preoperatively to 23.3 ± 2.1 postoperatively (P < 0.05). And the proportion of optimal outcomes was 88.1%. The ventral and dorsal heights of intervertebal disc were significantly higher than those before operation. The fusion rate was 95.2% and the incidence of adjacent segment degeneration 9.5%. There was no occurrence of such complications as secondary scoliosis, screw loosening, internal fixation failure and cage slippage. CONCLUSION: Unilateral pedicle screw fixation with lumbar interbody fusion is efficacious for lumber degenerative diseases with little surgical trauma.