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Spinal Cord Compression (spinal + cord_compression)
Kinds of Spinal Cord Compression Selected AbstractsCervical osteochondroma as a cause of spinal cord compression in a patient with hereditary multiple exostoses: Computed tomography and magnetic resonance imaging findingsJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2002Bayram Çirak SUMMARY Spinal cord compression is a rare but extremely serious complication of hereditary multiple exostoses (HME). Imaging of the spine is important for surgical planning and follow up. We present CT and MR findings in a male patient with HME who developed spinal cord compression from a cervical osteochondroma. Complete recovery was achieved following surgery. [source] Catheter Tip Granuloma Associated with Sacral Region Intrathecal Drug AdministrationNEUROMODULATION, Issue 4 2003Fernandez Julius MD Abstract Spinal cord compression from catheter tip granulomatous masses following intrathecal drug administration may produce devastating permanent neurologic deficits. Some authors have advocated intrathecal catheter placement below the conus medullaris to avoid the possibility of spinal cord involvement. Multiple cases of catheter tip granulomas in the thoracolumbar region have been reported. We present a unique case of a sacral region catheter tip inflammatory mass producing permanent neurologic deficits. A 71-year-old white male with a diagnosis of failed back surgery syndrome was referred to the senior author for evaluation. After more extensive conservative therapy, including spinal cord stimulation, failed to yield adequate pain relief, he was offered implantation of an intrathecal pump for opioid administration. Excellent pain relief was achieved in the postoperative period; however, three years after implantation, he presented with progressive saddle anesthesia and bowel/bladder incontinence. Magnetic resonance imaging demonstrated a space occupying lesion associated with the catheter tip. The patient underwent emergent second level complete sacral laminectomy with partial resection of an intradural extra-axial mass and removal of intrathecal catheter. At discharge, the patient had no restoration of neurologic function. Histologic examination of the mass confirmed a sterile inflammatory mass. It has been suggested that intrathecal catheters be placed below the conus medullaris to avoid the possibility of spinal cord involvement. We present an unusual case documenting devastating permanent neurologic deficits from a catheter tip granuloma in the sacral region. [source] Evaluation of decision criteria for detection of spinal cord compression based on cervical myelography in horses: 38 cases (1981,2001)EQUINE VETERINARY JOURNAL, Issue 1 2004J. Van Biervliet Summary Reasons for performing study: Different criteria have been described based on height reduction of the total myelographic contrast column and components of it as tests for compression of the spinal cord due to cervical stenotic myelopathy (CSM). Fifty percent height reduction of the dorsal myelographic column (DMC), <2 mm empiric height of the DMC and a 40% reduction of the ratio of stenosis calculated based on the height reduction of the entire dural diameter (DD) have been described as decision criteria for considering the test result positive. The reasons for selecting these decision criteria or their accuracies have rarely been reported. Objectives: To evaluate the accuracy of diagnostic criteria based on reduced height of the total myelographic column and components of it for diagnosing extradural spinal cord compression using different decision criteria, and make recommendations for consistent myelographic interpretation in horses suspected of having CSM. Methods: Four measurements were obtained by 2 readers in a retrospective sample population of 38 horses in which both cervical myelography and histopathological examination of the cervical spinal cord were performed. The prevalence of CSM in the sample was 50%. At intervertebral sites, the minimum heights of the DD and DMC were measured. At intravertebral sites, the maximum heights of the entire DD and DMC were obtained. Percent height reductions of the DMC and DD were determined as the ratio of minimum intervertebral height to maximum intravertebral height within the next cranial vertebra. Histological examination was used as the gold standard for determining the actual site of spinal cord compression. Sensitivity and specificity for the diagnostic criteria were estimated at each site in neutral and flexed neck positions using several different decision criteria. Conclusions: At C6-C7, in neutral or flexed neck position and using 20% reduction of DD, the test was highly sensitive and specific for CSM. At other sites, reduced height of the myelographic column generally was not accurate for diagnosing extradural spinal cord compression. Using 20% reduction of DD in neutral position at the mid-cervical sites, the test had only low sensitivity and high specificity. Flexion of the neck appeared to increase detection of spinal cord compression in the mid-cervical region, but also substantially increased the frequency of false-positive diagnoses. Potential relevance: By using the reported sensitivity and specificity estimates, readers may decide on a decision criterion for diagnosis of extradural spinal cord compression due to CSM. However, in planning a surgical correction, it is difficult to define a decision criterion that combines acceptable sensitivity and specificity, especially at the mid-cervical sites. [source] Efficacy of ibandronate for the treatment of skeletal events in patients with metastatic breast cancerEUROPEAN JOURNAL OF CANCER CARE, Issue 6 2009P. HERAS md HERAS P., KRITIKOS K., HATZOPOULOS A. & GEORGOPOULOU A.-P. (2009) European Journal of Cancer Care Efficacy of ibandronate for the treatment of skeletal events in patients with metastatic breast cancer Patients with breast carcinoma often develop bone metastases that carry a high risk of complications. A randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of ibandronate in patients with metastatic bone disease following breast cancer. The primary efficacy end point of the study was the proportion of patients who developed skeletal-related events (SREs, defined as pathologic fracture, spinal cord compression, radiation therapy to bone, change in anti-neoplastic therapy and surgery to bone). Secondary end points included time to first skeletal event, skeletal morbidity rate (events/year) and time to progression of bone lesions. In 150 patients (148,/2,) with breast carcinoma and bone metastases, treatment with intravenous ibandronate 6 mg over 15 min every 4 weeks for 24 months significantly reduced the proportion of patients who experienced an SRE compared with placebo (36% vs. 48%; P = 0.027). Time to first SRE was also delayed significantly (median 457 vs. 304 days; P = 0.007). Multiple event analysis showed that ibandronate reduced the risk of developing an SRE by 32% (hazard ratio = 0.69; 95% confidence interval 0.42,0.79; P = 0.003). In general, ibandronate was well tolerated with very rare grade 3 or 4 toxicity. In this study, ibandronate was shown to be significantly more effective than placebo as a treatment for metastatic bone disease from breast cancer using multiple end points. [source] Metastatic spinal cord compression: an oncological emergencyEUROPEAN JOURNAL OF CANCER CARE, Issue 5 2009IAIN LAWRIE mb, consultant in palliative medicine, mrcgp This module considers the identification and management of metastatic spinal cord compression. [source] Thoracic spinal cord compression by a rheumatoid noduleINTERNAL MEDICINE JOURNAL, Issue 3 2004Y. Levy No abstract is available for this article. [source] Osteological features in pure-bred dogs predisposing to cervical spinal cord compressionJOURNAL OF ANATOMY, Issue 5 2001S. BREIT Relative to body size, midsagittal and interpedicular diameters of the cranial and caudal aspects of cervical vertebral foramina (C3,C7) were found to be significantly (P < 0·05) larger in small breeds than in large breeds and Dachshunds, and also larger in Dachshunds (P < 0·05) than in large breeds. This condition increases the risk for spinal cord compression resulting from relative stenosis of the cervical vertebral foramina, especially in large dogs, and this is also exacerbated by the typical shape of the vertebral foramina (i.e. dorsoventrally flattened cranially and bilaterally narrowed caudally). Within large dogs those breeds highly predisposed to cervical spinal cord compression were Great Danes (the breed with the smallest midsagittal vertebral foramen diameters from cranial C6 to cranial T1) and Doberman Pinschers, because of the most strikingly cranially dorsoventrally narrowed cone-shaped vertebral foramina at C6 and C7. The existence of a small midsagittal diameter in the cranial cervical spine was a high risk factor predisposing to spinal cord compression in small breeds and Dachshunds. Remarkable consistency was noted between the spinal level of the maximum enlargement of the spinal cord which previously was reported to be at C6, and the site of maximum enlargement of the vertebral canal currently stated in Dachshunds and small breeds. In large breeds the maximum enlargement of the vertebral canal tended to be located more caudally at the caudal limit of C7. The average age at which large dogs were most susceptible to noxious factors causing abnormal growth of the pedicles was determined to be 16 wk. [source] Metastatic spinal cord compression: a review of practice and careJOURNAL OF CLINICAL NURSING, Issue 13-14 2010Lynn Kilbride Aim and objectives., The aim of this review was to address: (1) How is spinal stability assessed? (2) What is the role of bracing/should braces be used? (3) When is it safe to mobilise the patient? (4) What position should the patient be nursed in? Background., Controversy surrounds the care for patients with metastatic spinal cord compression (MSCC). There is some evidence to indicate that care for patients with MSCC is based on individual clinician preference rather than evidence-based guidelines which has been shown to cause delays and discrepancies in patient treatment. Design., A structured literature review to synthesise the available evidence about the management of MSCC. Methods., The following databases were searched: Medline, EMBASE, Cochrane Systematic Reviews Database, SIGN (Scottish Intercollegiate Guidelines Network), NICE (National Institute for Clinical Excellence), AMED (Allied and Complementary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health Literature) and BNI (British Nursing Index). Publications were selected from the past 10 years. The search yielded a total of 1057 hits, 755 abstracts were screened, and 73 articles were retrieved and examined. Thirty-five articles were included. Results., The findings identified a gap and evidence relating to spinal stability, bracing, patient mobilisation, and positioning is limited and may be inconclusive. It is important for patients with a poor prognosis that their preferences and quality of life are considered. Conclusion., Currently, the evidence base to underpin care is limited, and further research in this area is necessary for patients and healthcare professionals alike. Relevance to clinical practice., Patients who suffer from MSCC suffer numerous physical, psychological and social issues. Because of lack of consensus, the current guidelines to inform clinical decision-making of professional staff are of limited benefit. [source] Cervical osteochondroma as a cause of spinal cord compression in a patient with hereditary multiple exostoses: Computed tomography and magnetic resonance imaging findingsJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2002Bayram Çirak SUMMARY Spinal cord compression is a rare but extremely serious complication of hereditary multiple exostoses (HME). Imaging of the spine is important for surgical planning and follow up. We present CT and MR findings in a male patient with HME who developed spinal cord compression from a cervical osteochondroma. Complete recovery was achieved following surgery. [source] Association of spinal cord compression seen on magnetic resonance imaging with clinical outcome in 67 dogs with thoracolumbar intervertebral disc extrusionJOURNAL OF SMALL ANIMAL PRACTICE, Issue 11 2006V. Penning Objectives: To determine whether there is an association between the degree of transverse spinal cord compression detected by magnetic resonance imaging following thoracolumbar Hansen type 1 intervertebral disc disease in dogs and their presenting and postsurgical neurological status. Methods: Medical records of 67 dogs with surgically confirmed Hansen type 1 intervertebral disc disease (2000 to 2004) were reviewed to obtain the rate of onset of disease, duration of clinical signs and presurgical and postsurgical neurological grade. Percentage of spinal cord compression was determined on transverse T2-weighted magnetic resonance images. Linear regression was used to examine the association between spinal cord compression and each of the above variables. Chi-squared tests were used to examine associations among postsurgical outcome and presurgical variables. Results: Eighty-five per cent (57 of 67) of dogs were chondrodystrophoid. Mean spinal cord compression was 53 per cent (sd=219·7, range 14·3 to 84·9 per cent). There was no association between the degree of spinal cord compression and the neurological grade at presentation, rate of onset of disease, duration of clinical signs or postsurgical outcome, with no difference between chondrodystrophoid and non-chondrodystrophoid dogs. Clinical Significance: The degree of spinal cord compression documented with magnetic resonance imaging in dogs with thoracolumbar Hansen type 1 intervertebral disc disease was not associated with the severity of neurological signs and was not a prognostic indicator in this study. [source] The effects of MRI signal intensity changes and clinical manifestations on prognosis after surgical intervention for cervical spondylotic myelopathyORTHOPAEDIC SURGERY, Issue 2 2009Ying-ze Zhang MD Objective:, To investigate whether the magnetic resonance (MR) T2 image signal intensity ratio and clinical manifestations can predict the prognosis in patients with cervical spondylotic myelopathy (CSM). Methods:, A total of 73 patients treated with anterior, posterior, or posterior-anterior combined surgery for compressive cervical myelopathy were enrolled retrospectively in this study. 1.5 T magnetic resonance imaging (MRI) was performed on all patients before surgery. T2-weighted images (T2WI) of sagittal signal intensity were obtained of the cervical spinal cord, and the regions of interest (ROI) were taken by 0.05 cm2. MR T2WI of sagittal normal cord signal at the C7-T1 disc level were also obtained, and the ROI were taken by 0.3 cm2. Signal value was measured by computer and the signal ratio between regions 0.05 cm2 and 0.3 cm2 calculated. Where no intramedullary high signal intensity was noted on MR T2WI, the ROI were taken by 0.05 cm2 of the region of most severe spinal cord compression. The 73 patients were divided into three groups by hierarchical clustering analysis with signal intensity ratio (group 1: low signal intensity ratio; group 2: middle signal intensity ratio; group 3: high signal intensity ratio). Statistical analyses were performed with SPSS 11.0. Results:, There were significant differences between the three groups according to the recovery rate (P < 0.001), age (P= 0.003), duration of disease (P= 0.001), Babinski sign (P < 0.001), pre- and postoperative Japanese Orthopaedic Association (JOA) score (P= 0.006). With increases in both signal intensity ratio grade and age, the recovery rate and pre- and postoperative JOA scores gradually decreased, and the incidence of Babinski sign increased. There was no significant difference in sex among the three groups (P= 0.387). Multiple comparison tests further supported the above-mentioned results. Conclusion:, Patients with light or no intramedullary signal changes on T2WI had a good surgical outcome. However, increase of signal intensity ratio and occurrence of the pyramidal sign were associated with a poor prognosis after surgery. [source] Waldenstrom's macroglobulinemia presenting with spinal cord compression: A case reportAMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2006Hani Al-Halabi Abstract Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma characterized by a wide range of clinical presentations related to direct tumor infiltration and the production of IgM. Most commonly it presents with cytopenia, hepatosplenomegaly, lymphadenopathy, constitutional symptoms, and hyperviscosity syndrome. We report a case of WM in an 81-year-old man who initially presented with severe back pain. The patient had no peripheral lymphadenopathy or hepatosplenomegaly and his peripheral blood smear was normal. MRI of the spine revealed an epidural mass causing spinal cord compression at T9. Surgical decompression was performed and pathological analysis of the mass revealed a lymphoproliferative B-cell process. The diagnosis of WM was established after cytomorphologic and immunohistochemical analysis of the patient's bone marrow revealed the presence of a lymphoid/lymphoplasmacytoid-like bone marrow infiltrate along with an elevated serum IgM level. The patient responded both clinically and serologically to local radiotherapy. This case is unusual because the patient lacked all common clinical features of WM. This is the first reported case of epidural spinal cord compression as the initial manifestation of WM, adding to the spectrum of clinical presentations seen in this disease. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] NEUROLOGICAL DEFICIT AS A PRESENTATION OF OCCULT METASTATIC THYROID CARCINOMAANZ JOURNAL OF SURGERY, Issue 10 2006Mark Izzard Three cases of occult metastatic thyroid carcinoma presenting with neurological deficits are reviewed. In each case the patient's initial presentation was with symptoms of neurological deficiency secondary to a spinal cord compression. All patients received a combination of surgery, external beam radiotherapy and postoperative thyroxine treatment. Two of the three patients are alive and well, able to mobilize with minor neurological dysfunction. The diagnosis and management of the patients, as well as their outcomes are reviewed, with a discussion on further management issues alongside a review of the current published work. [source] Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compressionCANCER, Issue 15 2010Dirk Rades MD Abstract BACKGROUND: Based on an analysis of 1852 retrospectively evaluated patients with metastatic spinal cord compression (MSCC), a scoring system was developed to predict survival. This study was performed to validate the scoring system in a new data set. METHODS: The score included 6 prognostic factors: tumor type, interval between tumor diagnosis and MSCC, other bone or visceral metastases, ambulatory status, and duration of motor deficits. Scores ranged between 20 and 45 points, and patients were initially divided into 5 groups: those with 20 to 25 points, those with 26 to 30 points, those with 31 to 35 points, those with 36 to 40 points, and those with 41 to 45 points. To facilitate the clinical use of the score, the patients were regrouped into 3 groups: those with 20 to 30 points, those with 31 to 35 points, and those with 36 to 45 points. In this study, data of 439 new patients were included who were divided into the same prognostic groups as in the preceding study. RESULTS: In this study, the 6-month survival rates were 7% (for those with 20-25 points), 19% (for those with 26-30 points), 56% (for those with 31-35 points), 73% (for those with 36-40 points), and 90% (for those with 41-45 points), respectively (P < .0001). After regrouping, the 6-month survival rates were 14% (for those with 20-30 points), 56% (for those with 31-35 points), and 80% (for those with 36-45 points), respectively, in this study (P < .0001). CONCLUSIONS: In the current study, the difference in 6-month survival between the prognostic groups was found to be as significant as in the preceding study. Thus, this scoring system was considered valid to estimate survival of MSCC patients. The system could have been simplified by including only 3 instead of 5 prognostic groups. Cancer 2010. © 2010 American Cancer Society. [source] Prognostic factors for functional outcome and survival after reirradiation for in-field recurrences of metastatic spinal cord compression,CANCER, Issue 5 2008Dirk Rades MD Abstract BACKGROUND. The purpose of the current study was to retrospectively investigate clinical outcome and potential prognostic factors after reirradiation (Re-RT) for in-field recurrence of metastatic spinal cord compression (MSCC). METHODS. Re-RT with 1 × 8 Gy (n = 48), 5 × 3 Gy (n = 29), 5 × 4 Gy (n = 30), 7 × 3 Gy (n = 3), 10-12 × 2 Gy (n = 11), or 17 × 1.8 Gy (n = 3) was administered to 124 patients. Cumulative biologically effective dose (BED) (first course of RT plus re-RT) ranged from 77.5 Gy2 to 142.6 Gy2, and was ,120 Gy2 in 114 (92%) patients. Twelve potential prognostic factors were investigated for associations with motor function and survival. RESULTS. Motor function improved in 45 (36%) patients, was stable in another 62 (50%) patients, and deteriorated in 17 (14%) patients. Upon multivariate analyses, the effect of Re-RT on motor function was significantly associated with the effect of the first course of RT (P = .048), Eastern Cooperative Oncology Group (ECOG) performance status (P = .020), time to development of motor deficits before Re-RT (P = .002), and visceral metastases (P < .001). Survival was associated with ECOG performance status (P < .001), ambulatory status before Re-RT (P < .001), time to development of motor deficits (P = .018), and visceral metastases (P <.001). Re-RT dose schedule or cumulative BED had no significant impact on functional outcome or survival. Acute toxicity was mild, and late toxicity, such as radiation myelopathy, was not observed. CONCLUSIONS. Given the limitations of a retrospective study and the relatively short follow up after Re-RT, spinal reirradiation appeared to be effective and safe when the cumulative BED is ,120 Gy2. Motor function after Re-RT was associated with the effect of first irradiation, performance status, time to development of motor deficits, and visceral metastases, whereas the Re-RT schedule had no significant impact. Cancer 2008. © 2008 American Cancer Society. [source] Kaposi sarcoma of the musculoskeletal systemCANCER, Issue 6 2007A review of 66 patients Abstract Kaposi sarcoma (KS) of bone and skeletal muscle is unusual. In this report, the authors review 66 published patients with KS who had involvement of the musculoskeletal system reported from 1925 to 2006. In only 3 patients was acquired immunodeficiency syndrome (AIDS)-related KS identified within skeletal muscle. Osseous KS lesions were more frequent and occurred with African, classic, and AIDS-related KS and occurred rarely in transplantation-associated KS. Patients seldom were asymptomatic. They usually had bone pain with limited mobility or infrequently developed serious sequelae like spinal cord compression. Locally aggressive African and classic KS lesions typically involved the peripheral skeleton; whereas, in patients with AIDS, the axial (vertebrae, ribs, sternum, and pelvis) and/or maxillofacial bones more commonly were involved. Almost all patients had concomitant nonosseous KS lesions. Joint involvement was exceptional, and pathologic fractures were not observed. Computed tomography scans and magnetic resonance images were better at detecting osseous KS lesions, which frequently went undetected on plain x-ray films or bone scans. Pathologic diagnosis was important to exclude similar lesions like bacillary angiomatosis. Treatment options, including surgery and, in more recent patients, radiation and/or chemotherapy, had limited success. Cancer 2007 © 2007 American Cancer Society. [source] Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesionCANCER, Issue 1 2004Lee S. Rosen M.D. Abstract BACKGROUND Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial. METHODS Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3,4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone. RESULTS Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]). CONCLUSIONS The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36,43. © 2003 American Cancer Society. [source] Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinomaCANCER, Issue 5 2003Allan Lipton M.D. Abstract BACKGROUND The objective of this study was to assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to renal cell carcinoma (RCC). METHODS A retrospective subset analysis of patients with RCC enrolled in a multicenter, randomized, placebo-controlled study of zoledronic acid was performed. Patients were randomized to receive zoledronic acid (4 or 8 mg as a 15-minute infusion) or placebo with concomitant antineoplastic therapy every 3 weeks for 9 months. The primary efficacy analysis was the proportion of patients with one or more skeletal-related events (SREs), which were defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate (events per year), disease progression, and multiple event analysis. RESULTS In this subset of 74 patients with RCC, zoledronic acid (4 mg) was found to significantly reduce the proportion of patients with an SRE (37% vs. 74% for placebo; P = 0.015). Similarly, zoledronic acid significantly reduced the mean skeletal morbidity rate (2.68 vs. 3.38 for placebo; P = 0.014) and extended the time to the first event (median not reached vs. 72 days for placebo; P = 0.006). A multiple event analysis demonstrated that the risk of developing an SRE was reduced by 61% compared with placebo (hazard ratio of 0.394; P = 0.008). The median time to progression of bone lesions was significantly longer for patients who were treated with zoledronic acid (P = 0.014 vs. placebo). Zoledronic acid appeared to be well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and emesis. CONCLUSIONS Zoledronic acid (4 mg as a 15-minute infusion) demonstrated significant clinical benefit in patients with bone metastases from RCC, suggesting that further investigation of zoledronic acid in this patient population is warranted. Cancer 2003;98:962,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11571 [source] | ||||||||||||||||||||||