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C Nos

Publications and source records attributed to C Nos.

At least 19 recordsLinked to original sources

Baseline MRI predicts future attacks and disability in clinically isolated syndromes.

OBJECTIVE: To determine the relation between baseline MRI and both conversion to multiple sclerosis (MS) and development of disability in a cohort of patients with clinically isolated syndromes (CIS). METHODS: From 1995 to 1998, 175 consecutive patients with CIS underwent brain MRI within 3 months of their first attack and again 12 months and 5 years later. We studied the number and location of lesions at baseline and development of new T2 lesions. We also analyzed conversion to MS and development of disability (Expanded Disability Status Scale [EDSS] > or = 3.0). RESULTS: We included 156 patients with CIS followed for a median of 7 years. Compared to the reference group with 0 Barkhof criteria at baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low, medium, and high conversion risk. EDSS at year 5 correlated with baseline number of Barkhof criteria (r = 0.46, p < 0.0001). When categorizing by number of baseline lesions, similar results were seen. Patients with a baseline MRI with three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for reaching EDSS > or = 3.0. Only 10% of the latter had disability at year 5, but 40% reached this at 8 years. CONCLUSIONS: Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.

Adult↗

Fatigue in multiple sclerosis persists over time: a longitudinal study.

BACKGROUND AND OBJECTIVE: Fatigue is one of the most frequent symptoms in multiple sclerosis (MS) but there is a lack of knowledge about its behaviour over time. The aim of our study was to investigate changes in fatigue in a large cohort of MS patients and to determine the relationship between changes in disability and depression with changes in fatigue severity. METHODS: We studied fatigue in 227 MS consecutive patients and again after one year. During the clinical interview, we recorded the patient's degree of disability using the Expanded Disability Status Scale and relapses; fatigue was measured by means of the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) and depression was measured by the Beck Depression Inventory (BDI). RESULTS: After a mean follow-up of 18 months, 86.8% of patients who were fatigued at study onset remained in a fatigued status, whereas 25% of those without fatigue at onset had become fatigued at the end of follow-up. We observed that only variations on BDI scores positively correlate with variations on fatigue scales, mainly with MFIS (r = 0.49, p < 0.0001). An increase of BDI score was the factor that best predicted the increase of fatigue over time. No differences in the increase of fatigue were found between patients with and without progression of disability during the follow-up period, or between patients with or without relapses. CONCLUSIONS: Fatigue in MS persists over time. Changes in mood status but not in disability are related to changes in fatigue in MS patients.

Adult↗

Neuromyelitis optica diagnosis in clinically isolated syndromes suggestive of multiple sclerosis.

The authors assessed the extent of overlap between current diagnostic criteria of neuromyelitis optica (NMO) and multiple sclerosis (MS) by applying NMO criteria to a large cohort of 320 patients with clinically isolated syndromes (CIS). Twenty-three (7.2%) patients fulfilled NMO absolute criteria at some time and 1 (0.3%) also fulfilled one major supportive criterion. Therefore, even by systematically applying NMO criteria in patients with CIS, NMO diagnosis is reached infrequently.

Adult↗

[Spanish adaptation of the disease-specific questionnaire MSQOL-54 in multiple sclerosis patients].

INTRODUCTION: The Multiple Sclerosis Quality of Life 54 (MSQOL-54) is a health-related quality of life specific questionnaire for multiple sclerosis (MS) patients. The objective of this study was to develop the Spanish version of the MSQOL-54 and to obtain a conceptually equivalent version to the original one for its use in patients with MS in the first phase of the project. METHODS: A transcultural adaptation procedure was designed according to the following phases: a) two independent translations made by bilingual native Spanish speaking translators (forward translation); b) a revision of the items by an expert panel; c) a back translation by a bilingual native English speaking person; d) comparison with the original version (expert panel and advise by the original authors), and e) cognitive debriefing (interviews with subjects with MS) to test the comprehension and feasibility of the instrument. RESULTS: Ten interviews were carried out with 5 men and 5 women with MS, aged 21 to 54 years, with different education levels and EDSS scores ranging from 1,0 to 8,0. Most of the patients found the questionnaire easy to fill out and the understanding favorable. Only one item (item 51) was modified after the cognitive debriefing to improve its comprehension. Finally, a final pretest version was obtained. CONCLUSIONS: The procedure carried out maximizes the conceptual equivalence between the original MSQOL-54 and the translated version and shows that the Spanish pre-test version is comprehensible and its administration feasible in patients with MS. The psychometric properties must be evaluated in the next phase of the project.

Activities of Daily Living↗

Does the Modified Fatigue Impact Scale offer a more comprehensive assessment of fatigue in MS?

BACKGROUND: As a symptom of multiple sclerosis (MS), fatigue is difficult to manage because of its unknown etiology, the lack of efficacy of the drugs tested to date and the absence of consensus about which would be the ideal measure to assess fatigue. OBJECTIVE: Our aim was to assess the frequency of fatigue in a sample of MS patients and healthy controls (HC) using two fatigue scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) with physical, cognitive and psychosocial subscales. We also studied the relationship fatigue has with depression, disability and interferon beta. METHODS: Three hundred and fifty-four individuals (231 MS patients and 123 HC) were included in this cross-sectional study. Fatigue was assessed using the FSS and MFIS. Depression was measured by the Beck Depression Inventory (BDI), and disability by the Expanded Disability Status Scale (EDSS). A status of fatigue was considered when the FSS > or =5, of non-fatigue when the FSS < or =4, and scores between 4.1 and 4.9 were considered doubtful fatigue cases. RESULTS: Fifty-five percent of MS patients and 13% of HC were fatigued. The global MFIS score positively correlated with the FSS in MS and HC (r =0.68 for MS and r =0.59 for HC, p <0.0001). Nonetheless, the MFIS physical subscale showed the strongest correlation score with the FSS (r =0.75, p <0.0001). In addition, a prediction analysis showed the physical MFIS subscale to be the only independent predictor of FSS score (p <0.0001), suggesting other aspects of fatigue, as cognition and psychosocial functions, may be explored by the FSS to a lesser extent. Depression also correlated with fatigue (r =0.48 for the FSS and r =0.7 for the MFIS, p <0.0001) and, although EDSS correlated with fatigue as well, the scores decreased after correcting for depression. Interferon beta showed no relationship with fatigue. CONCLUSIONS: Fatigue is a frequent symptom found in MS patients and clearly related with depression. Each fatigue scale correlates with one another, indicating that they are measuring similar constructs. Nevertheless, spheres of fatigue as cognition and psychosocial functions are probably better measured by the MFIS, although this hypothesis will need to be confirmed with appropriate psychometrical testing.

Adult↗

Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: a randomized trial.

OBJECTIVE: To compare the efficacy of acetaminophen, ibuprofen, and prednisone in the treatment of interferon beta-1a (IFNbeta-1a) flu-like syndrome (FLS). METHODS: Patients with relapsing-remitting multiple sclerosis initiating treatment with IM IFNbeta-1a were randomized in a multicenter, randomized, double-blind, controlled trial to receive acetaminophen 500 mg before and 6 and 12 hours after each injection, ibuprofen 400 mg before and 6 and 12 hours after each injection, or prednisone 60 mg daily for 1 week, plus tapering. Patients were instructed to keep a daily diary of fever severity, myalgia, chills, headache, and asthenia for 27 days. The sum of the scores of individual symptoms was used to obtain a daily FLS index. The primary outcome was the FLS index area under the curve (AUC) corrected by the number of measurement days. RESULTS: Eighty-four patients were randomized at 11 hospitals: acetaminophen (n = 28), ibuprofen (n = 28), and corticosteroids (n = 28). No differences were detected between treatments in the mean AUC of the FLS index. With limitation of the analysis to the days of IM IFNbeta-1a injection, differences favoring ibuprofen were observed in the mean FLS index (p = 0.0007). CONCLUSIONS: No prophylactic treatment for flu-like syndrome seems to be superior to another in terms of overall well-being during the first month of IM IFNbeta-1a therapy. However, ibuprofen confers better control of symptoms immediately following IM IFNbeta-1a injection.

Acetaminophen↗

Characteristics and outcome of 1755 operable breast cancers in women over 70 years of age.

From 1981 to 1995, 1755 patients aged 70 years or over who had nonmetastatic unilateral breast carcinoma received curative local or regional treatment in our institute. Median follow-up was 8 years. The median age of these patients was 75 years (range: 70-94), and 86% were under 81 years of age. Tumors were classed as T3-4 in 24% of them; 18% had N1b/N2 tumors, and in 12% grade 3 disease was present. Only 19% were both ER and PR negative. The S phase fraction was <5% in 79% of patients. In 1046 patients (60%) modified radical mastectomy was performed, while 20% underwent lumpectomy and in 20% radiotherapy was the only treatment administered. Adjuvant endocrine therapy was given in 463 (26%) cases, and only 3% of patients received chemotherapy. The median overall survival time was 121 months. The overall cancer-related death rate was 49%. The 10-year disease-free survival (DFS) rate was 64%, and the 10-year local relapse rate was 14%. Prognostic factors determined on univariate analysis were tumor size, clinical nodal status (ER and PR), and grade. No significant difference in outcome was observed between mastectomy and conservative treatment. Parameters for which correlations with DFS were found on multivariate analysis were clinical nodal status (P < 0.0001), tumor size (P < 0.0001), ER (P < 0.0001), and PR (P = 0.04). Breast cancer in elderly women is frequently hormone-dependent (81%) with a low proliferation index. Prognostic factors are the same as in younger postmenopausal patients. More than 50% of these patients died from a cause other than their breast cancer.

Aged↗

[Breast-conserving therapy of breast cancer].

Breast-conserving treatment for breast cancer combines lumpectomy, axillary nodes treatment and radiotherapy of the breast. Conservative surgery and radiotherapy is now the standard treatment for unifocal, non inflammatory tumors, less than 3 cm in diameter. The widespread use of mammographic screening leads to a significant increase in the proportion of non palpable breast carcinomas, and has contributed to increase the proportion of breast conserving treatments. Neoadjuvant treatments (chemotherapy, radiotherapy and hormonotherapy) can also extend the indications of breast conservation to breast carcinomas larger than 3 cm. Furthermore, in the last ten years, new surgical procedures (sentinel node biopsy, oncoplastic surgery, minimal invasive surgery) have been developed, increasing the surgical possibilities. After a learning phase to establish new standards for these procedures, all these techniques are now part of our standard surgical apparel, thus extending the possibilities of breast conserving surgery.

Adult↗

Clinical and genetic features of human prion diseases in Catalonia: 1993-2002.

We describe the clinical and genetic characteristics of the 85 definite or probable human prion diseases cases died between January 1993 and December 2002 in Catalonia (an autonomous community of Spain, 6 million population). Seventy-three (86%) cases were sporadic Creutzfeld-Jakob diseases (sCJD) (49 definite, 24 probable), with a median age at onset of 66 years. The clinical presentation was dementia in 29 cases, ataxia in 14 and visual symptoms in five. The median survival was 3 months. The 14-3-3 assay was positive in 93% cases, 62% presented periodic sharp wave complexes (PSWC) in EEG but only 18% the typical signs on MRI. Forty-eight sCJD were studied for codon 129 PRNP polymorphism: 69% were methionine/methionine (M/M), 14.5% valine/valine (V/V) and 16.5% M/V. Six out of seven V/V cases did not present PSWC and in two survival was longer than 20 months. Eleven cases (13%) were genetic: five familial fatal insomnia and six familial CJD (fCJD). Up to four (67%) fCJD lacked family history of disease, two presented seizures early at onset and one neurosensorial deafness. The only iatrogenic case was related to a dura mater graft. No case of variant CJD was registered. The study confirms in our population the consistent pattern reported worldwide on human prion diseases. Atypical features were seen more frequently in sporadic 129 V/V CJD and fCJD cases.

14-3-3 Proteins↗

Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer.

There is increasing statistical evidence that the presence of tumour cells in bone marrow detected by immunocytochemistry represents an important prognostic indicator in breast cancer, but their individual capacity to become clinical metastases is unknown. The aim of this study was to assess the proliferative capacity of these occult metastatic cells in the bone marrow of patients with various stages of breast cancer. We obtained bone marrow aspirates from 60 patients with breast cancer before treatment with chemotherapy: 17 stage II, 12 stage III and 31 stage IV. After bone marrow culture for 6-34 days (median: 17 days) under specific cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 40 patients (66%). Expansion of tumour cells was poorly correlated with tumour cell detection on primary screening (P=0.06). There was a nonsignificant correlation between the number and the presence of expanded tumour cells and the UICC stage of the patients. On primary screening, tumour cell detection was positive in 56% of patients and was correlated with clinical UICC stage (P=0.01). However, with a median follow-up of 23 months, expansion of tumour cells from bone marrow was associated with decreased patient survival (P=0.04), whereas the survival difference according to detection of CK-positive cells on primary screening was not statistically significant. In conclusion, viable tumour cells can be detected in the bone marrow of breast cancer patients. Their proliferative potential could be predictive of outcome and deserves further investigation.

Adult↗

New diagnostic criteria for multiple sclerosis: application in first demyelinating episode.

BACKGROUND: Recently developed diagnostic criteria for MS (McDonald criteria) indicate that in patients with a single demyelinating episode (clinically isolated syndromes [CIS]), evidence for dissemination in space and time, essential for diagnosis, may be provided by MRI. OBJECTIVE: To assess the usefulness of these new criteria in patients with CIS suggestive of MS. METHODS: A total of 139 patients with CIS followed for a median of 3 years underwent brain MRI within 3 months of their first attack and again 12 months later. The number and location of lesions at baseline, the development of new lesions at follow-up, and the results of CSF examination (which, if positive, requires fewer MR abnormalities for diagnosis) were analyzed. The new McDonald criteria (incorporating MRI) were compared to the existing Poser diagnostic criteria and their accuracy was evaluated. RESULTS: At 12 months, 11% had clinically definite MS according to the Poser criteria compared to 37% with the McDonald criteria. Eighty percent of patients fulfilling these new criteria developed a second clinical episode within a mean follow-up of 49 months. The new criteria showed a sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to clinically definite MS. CONCLUSION: One year after symptom onset, more than three times as many patients with CIS were diagnosed with MS using new diagnostic criteria incorporating MRI results compared to older criteria. However, the proposed MRI criteria require further prospective studies to optimize sensitivity and specificity.

Adolescent↗

Prediction of tumour involvement in remaining axillary lymph nodes when the sentinel node in a woman with breast cancer contains metastases.

BACKGROUND: In a significant proportion of women with breast cancer, the sentinel node is the only involved node in the axilla. The purpose of this study was to identify factors associated with histologically positive non-sentinel lymph nodes. METHODS: Between 1997 and 2002, 800 women with early breast cancer underwent sentinel node biopsy. In 263 patients the node contained metastases, including 83 with micrometastases detected by immunohistochemistry (IHC), 40 micrometastases detected on haematoxylin, eosin and safranine (HES) staining, and 140 macrometastases. All clinical and histological criteria were recorded and analysed with reference to histology of the non-sentinel node. RESULTS: The risk of metastasis in the non-sentinel lymph node was related to the volume of the tumour in the sentinel node. Non-sentinel nodes were involved in five (6.0 per cent) of 83 women when the sentinel node contained only micrometastatic cells detected on IHC, and in three (7.5 per cent) of 40 women when micrometastases were detected by HES, compared with 55 (39.3 per cent) of 140 when the sentinel node contained macrometastases on HES staining. Univariate analysis revealed a significant association between non-sentinel node involvement and type of metastasis within the sentinel node, clinical primary tumour size, palpable axillary lymph nodes before operation, pathological primary tumour size and the presence of peritumoral lymphovascular invasion. On multivariate analysis, the type of metastasis within the sentinel node (P < 0.001), histological tumour size greater than 20 mm (P = 0.017) and the presence of palpable axillary nodes before operation (P = 0.014) remained significant. CONCLUSION: Clinical and pathological factors associated with sentinel node histology can reliably predict women for whom further axillary clearance is recommended, but it is not yet possible to determine a subgroup of patients in whom the sentinel node is the only involved node and for whom further axillary treatment may be unnecessary.

Adult↗

Myelopathy in seronegative Sjögren syndrome and/or primary progressive multiple sclerosis.

OBJECTIVE: The relationship between multiple sclerosis (MS) and Sjögren syndrome (SS) is controversial. Nine patients, previously diagnosed with primary progressive MS (PPMS) and who fulfilled the diagnostic criteria for SS, are described. METHODS: The European classification criteria for SS were used to study nine PPMS patients that complained of sicca complex symptoms. The following tests were performed: Schirmer test, rose bengal staining, salivary scintigraphy, minor salivary gland biopsy and serologic tests (antibodies Ro/SS-A, La/SS-B and antinuclear antibodies). RESULTS: The nine patients met criteria to be diagnosed with SS (at least four criteria). All patients were women with a mean age of 46.6 years at symptom onset. Spastic paraparesis was the presenting symptom in all patients, and spinal cord magnetic resonance imaging (MRI) showed abnormalities in most; anti-Ro and anti-La antibodies were mostly negative. CONCLUSIONS: Some MS patients, predominantly women over 45 years of age, with progressive spastic paraparesis, antiextractable nuclear antigen antibodies (Ro/SS-A or La/SS-B) negative and with abnormalities in spinal cord MRI, may have SS as an additional or alternative diagnosis.

Adult↗

[Descriptive study of first visits in a multiple sclerosis specialised unit].

BACKGROUND: The need for optimal care has led to implementation of multiple sclerosis care units, specialised in diagnosis and follow-up of multiple sclerosis patients. Since information on multiple sclerosis prognosis is crucial, accurate diagnosis is one of their major roles. METHOD: Prospective analysis of first visits during a year (origin and diagnosis) at the Unidad de Neuroinmunología Clínica of Hospital Vall d'Hebron. RESULTS: A total of 437 first visits were analysed; a moderate agreement (kappa = 0.468) between referral diagnoses and diagnosis at follow-up was obtained; agreement was very good (kappa = 0.844) between diagnosis at first visit and diagnosis at follow-up. In the subgroup of 200 patients with a demyelinating disease on follow-up after one year, 37.6% of referrals came from other non-specialised centers and 40.6% from our own center. CONCLUSION: Specialised care units enhance diagnostic precision; direct influence zone and non-specialised centers referrals are their more important sources of patients.

Adolescent↗

[Sentinel node biopsy in breast cancer. Improving reliability of results].

OBJECTIVES: Sentinel node (SN) biopsy in breast cancer has a relatively high false negative rate, frequently exceeding 10%, for predicting the axillary nodal status. When the SN is identified using the patent blue dye technique, we advocate subjecting it to a verification of its blue colour by the pathologist as quality control. PATIENTS AND METHODS: One hundred and twenty-two consecutive patients with an operable breast cancer underwent a SN biopsy procedure with patent blue dye injected peritumourally. The SN biopsy was routinely followed by an axillary dissection. Initially each SN was examined histopathologically in a standard fashion. Then the non metastatic SNs were checked to ensure that they were blue by macroscopic examination of the paraffin blocks in which they had been embeded. Finally, a search for micrometastasis using immunohistochemistry was performed on all SNs which were non metastatic and confirmed to be blue. RESULTS: In 107 (88%) of 122 patients a SN was identified by the surgeon. After standard histological examination, 32 of 107 SNs proved to contain metastatic tumour. 75 SNs were not metastatic, of which 3 were false negative which would have given a false negative rate of 8.5%(3/35). After checking the paraffin blocks of the 75 non metastatic SN, 62 of the 75 were confirmed blue from which there were 2 false negatives giving a false negative rate of 5.8% (2/34). The 62 confirmed blue nodes were then assessed for micrometastasis. 20 nodes proved to be micrometastatic and there remained one false negative. This gave a final false negative rate of 1.8% (1/53). The false negative rate was thus reduced from 8.5% to 1.8% after colour quality control and identification of micrometastasi. DISCUSSION: In this series the procedure of histopathological quality control of the SN identified with the patent blue only technique resulted in a valuable reduction in the false negative rate.

Adult↗

The impact of the introduction of the 14-3-3 protein assay in the surveillance of sporadic Creutzfeldt-Jakob disease in Catalonia.

The 14-3-3 assay in the CSF has a high predictive value for the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). Our objective was to analyse the trends in mortality and incidence rates of CJD in Catalonia, an autonomous community of Spain, setting the cut off point the date when the 14-3-3 assay was incorporated to our CJD surveillance system. Only definite and probable cases according to the criteria adapted from Masters and colleagues were included for the analysis. Familial cases were excluded after genetic analysis of the PrP gen. We found a quasi threefold increase in the incidence and mortality rates for CJD after introduction of the 14-3-3 assay in our surveillance system in 1997 as compared with the period 1993-1996. Our findings suggest an improvement of case ascertainment in part due to the introduction of the 14-3-3 assay in the surveillance system.

14-3-3 Proteins↗

Sentinel lymph node detection for breast cancer: which patients are best suited for the patent blue dye only method of identification?

BACKGROUND: The objectives of this study were, first, to define the preoperative criteria for using solely the blue dye method and, second, to decrease its operator dependence in predicting axillary lymph node status. METHODS: Two hundred fifty-three women consecutively identified with operable breast cancer underwent sentinel lymph node (SLN) detection by the patent blue dye method followed by completion axillary lymph node dissection. A standard pathological examination was performed for all SLN. Then, a pathological color quality assessment (PCQA), which checked for the presence of the blue dye, was performed on the paraffin blocks of the nonmetastatic SLN. Six preoperative identifiable variables likely to influence the detection rate were examined. RESULTS: The surgical detection (sd) rate was 84% (213 of 253) and the PCQA rate was 73% (185 of 253). Only breast size (sd, P = .0005; PCQA, P = .0007) and body mass index < or =30 (sd, P = .005; PCQA, P = .0007) were significant for SLN identification. Multivariate analysis revealed two independent factors influencing SLN identification: breast size (sd, P = .0001; PCQA, P = .002) and the timing of injection-injection prior to lumpectomy (sd, P = .04). CONCLUSIONS: The optimal patient features for identifying the SLN by the patent blue dye method are small or medium-sized breasts, low body fat, and that the procedure is carried out prior to tumor excision. The PCQA offers a useful second assessment of the surgically removed SLN, introducing an independent element of quality control.

Adult↗