Cause-specific mortality after a breast cancer diagnosis: a cohort study of 10,195 women in Girona and Tarragona.

INTRODUCTION: Evidence suggests an excess of long-term mortality due to cardiovascular diseases, second tumours and other causes in patients diagnosed with invasive breast cancer (BC). Our aim was to assess this risk of death in a cohort of patients diagnosed with BC in Girona and Tarragona, northeastern Spain. MATERIALS AND METHODS: Using data from the cancer registries in these areas, a population-based cohort study was carried out including all the women diagnosed with BC during 1985-2004 and followed up until December 31st 2014 (N = 10,195). The standardised mortality ratios (SMRs) were calculated for causes other than BC in the cohort at 10 years (periods 1985-1994/1995-2004) and 20 years (period 1985-1994). The impact of competing causes of death in the long-term survival was evaluated through competing risk analysis. RESULTS: The SMRs at 10 and 20 years for all-cause mortality, except BC, were 1.21 and 1.22. The main causes of mortality showing statistically significant SMR at 10 years were other tumours (colon, lung, corpus uteri, ovary, and haematological), diabetes mellitus, diseases of the nervous system, cardiovascular diseases (after BC, the second competing cause of death among patients diagnosed > 69 years) and diseases of the kidney. Globally, the 10-year SMR was higher in the first period. After 20 years of follow-up (1985-1994 cohort), there were 48.5 excess deaths per 10,000 patient-years for causes other than BC. CONCLUSIONS: Women who did not die from BC at 10 or 20 years after the BC diagnosis had 20% higher risk of dying from other causes than women without BC. This excess risk must be clinically considered during 20 years after the BC diagnosis.

Estudios funcionales de variantes de DKK1 presentes en la población general / Functional studies of DKK1 variants present in the general population

Objetivo: En las últimas décadas se han identificado genes asociados a la masa ósea y al riesgo de fractura osteoporótica, varios de los cuales pertenecen a la vía de Wnt. En este proyecto se estudió la funcionalidad de 7 mutaciones de cambio de sentido del gen DKK1 -un inhibidor de la vía de Wnt- presentes en la población general. Material y métodos: Se realizaron estudios in vitro del gen reportero luciferasa para medir la actividad de la vía de Wnt en presencia o ausencia de DKK1 silvestre o mutada, y estudios de western blot, para evaluar si las distintas mutaciones afectan a su síntesis y/o a su estabilidad. Resultados: La proteína DKK1 con la variante p.Ala41Thr presenta menor actividad inhibidora de la vía en comparación con la proteína silvestre. También se observaron diferencias significativas entre los experimentos realizados en ausencia de DKK1 y los que incluyen DKK1 con la mutación p.Ala41Thr. Los western blots mostraron que la cantidad de proteína era similar para todas las variantes, tanto las mutadas como la silvestre, por lo que la pérdida de actividad de p.Ala41Thr no parecía deberse a falta de proteína. El resto de las mutaciones no presentaron un comportamiento diferente al de la proteína DKK1 silvestre. Conclusiones: La variante de cambio de sentido p.Ala41Thr de la proteína DKK1, con una frecuencia poblacional de 0,013%, presenta una pérdida parcial de su función inhibidora, que no es debida a la falta de expresión de ésta. Esta variante génica podría conllevar un aumento de la densidad mineral ósea en las personas de la población general portadoras de esta mutación

Objective: In recent decades, genes associated with bone mass and osteoporotic fracture risk have been identified, several of which belong to the Wnt pathway. In this project, the functionality of 7 missense mutations of the gene DKK1-an inhibitor of the Wnt pathway- present in the general population was studied. Material and methods: In vitro studies of the luciferase reporter gene were carried out to measure Wnt pathway activity in the presence or absence of wild-type or mutated DKK1, and western blot studies, to evaluate if the different mutations affect its synthesis and/or stability. Results: The DKK1 protein with the p.Ala41Thr variant shows lower pathway inhibitory activity compared to the wild-type protein. Significant differences were also observed between the experiments performed in the absence of DKK1 and those that include DKK1 with the p.Ala41Thr mutation. Western blots showed that the amount of protein was similar for all variants, both mutated and "wild-type, so the loss of p.Ala41Thr activity did not seem to be due to a lack of protein. The rest of the mutations did not show different behavior from that of the wild DKK1 protein. Conclusions: The missense variant p.Ala41Thr of the DKK1 protein, with a population frequency of 0.013%, shows a partial loss of its inhibitory function, which is not due to the lack of expression. This gene variant could lead to an increase in bone mineral density in those people in the general population who carry this mutation

Long-term crude probabilities of death among breast cancer patients by age and stage: a population-based survival study in Northeastern Spain (Girona-Tarragona 1985-2004)

Background: We provide population-based long-term survival indicators of breast cancer patients by quantifying the observed survival, and the probabilities of death due to breast cancer and to other causes by age and tumor stage at diagnosis. Methods; We included a total of 10,195 female patients diagnosed before 85 years with invasive primary breast cancer in Girona and Tarragona during the periods 1985-1994 and 1995-2004 and followed-up until December 31st 2014. The survival indicators were estimated at 5, 10, 15 and 20 years of follow-up comparing diagnostic periods. Results: Comparing diagnostic periods: I) the probability of death due to other causes did not change; II) the 20-year survival for women diagnosed ≤ 49 years increased 13% (1995-2004 = 68%; 1985-1994:55%), whereas their probability of death due to breast cancer decreased at the same pace (1995-2004 = 29%; 1985-1994 = 42%); III) at 10 years of follow-up, decreases in the probabilities of death due to breast cancer across age groups switched from 11 to 17% resulting in a risk of death reduction of 19% after adjusting by stage. During 1995-2004, the stage-specific 10-year probabilities of death due to breast cancer switched from: 3-6% in stage I, 18-20% in stage II, 34-46% in stage III and surpassed 70% in stage IV beyond 5 years after diagnosis. Conclusions: In our study, women diagnosed with breast cancer had higher long-term probability to die from breast cancer than from other causes. The improvements in treatment and the lead-time bias in detecting cancer in an early stage resulted in a reduction of 19% in the risk of death between diagnostic periods

No disponible

Long-term crude probabilities of death among breast cancer patients by age and stage: a population-based survival study in Northeastern Spain (Girona-Tarragona 1985-2004).

BACKGROUND: We provide population-based long-term survival indicators of breast cancer patients by quantifying the observed survival, and the probabilities of death due to breast cancer and to other causes by age and tumor stage at diagnosis. METHODS: We included a total of 10,195 female patients diagnosed before 85 years with invasive primary breast cancer in Girona and Tarragona during the periods 1985-1994 and 1995-2004 and followed-up until December 31st 2014. The survival indicators were estimated at 5, 10, 15 and 20 years of follow-up comparing diagnostic periods. RESULTS: Comparing diagnostic periods: I) the probability of death due to other causes did not change; II) the 20-year survival for women diagnosed ≤ 49 years increased 13% (1995-2004 = 68%; 1985-1994:55%), whereas their probability of death due to breast cancer decreased at the same pace (1995-2004 = 29%; 1985-1994 = 42%); III) at 10 years of follow-up, decreases in the probabilities of death due to breast cancer across age groups switched from 11 to 17% resulting in a risk of death reduction of 19% after adjusting by stage. During 1995-2004, the stage-specific 10-year probabilities of death due to breast cancer switched from: 3-6% in stage I, 18-20% in stage II, 34-46% in stage III and surpassed 70% in stage IV beyond 5 years after diagnosis. CONCLUSIONS: In our study, women diagnosed with breast cancer had higher long-term probability to die from breast cancer than from other causes. The improvements in treatment and the lead-time bias in detecting cancer in an early stage resulted in a reduction of 19% in the risk of death between diagnostic periods.

Assessing predicted age-specific breast cancer mortality rates in 27 European countries by 2020

Background. We assessed differences in predicted breast cancer (BC) mortality rates, across Europe, by 2020, taking into account changes in the time trends of BC mortality rates during the period 2000-2010. Methods. BC mortality data, for 27 European Union (EU) countries, were extracted from the World Health Organization mortality database. First, we compared BC mortality data between time periods 2000-2004 and 2006-2010 through standardized mortality ratios (SMRs) and carrying out a graphical assessment of the age-specific rates. Second, making use of the base period 2006-2012, we predicted BC mortality rates by 2020. Finally, making use of the SMRs and the predicted data, we identified a clustering of countries, assessing differences in the time trends between the areas defined in this clustering. Results. The clustering approach identified two clusters of countries: the first cluster were countries where BC predicted mortality rates, in 2020, might slightly increase among women aged 69 and older compared with 2010 [Greece (SMR 1.01), Croatia (SMR 1.02), Latvia (SMR 1.15), Poland (SMR 1.14), Estonia (SMR 1.16), Bulgaria (SMR 1.13), Lithuania (SMR 1.03), Romania (SMR 1.13) and Slovakia (SMR 1.06)]. The second cluster was those countries where BC mortality rates level off or decrease in all age groups (remaining countries). However, BC mortality rates between these clusters might diminish and converge to similar figures by 2020. Conclusions. For the year 2020, our predictions have shown a converging pattern of BC mortality rates between European regions. Reducing disparities, in access to screening and treatment, could have a substantial effect in countries where a non-decreasing trend in age-specific BC mortality rates has been predicted (AU)

No disponible

Predicting the cancer burden in Catalonia between 2015 and 2025: the challenge of cancer management in the elderly.

BACKGROUND: Developing effective cancer control programmes requires information on the future cancer burden in an ageing population. In our study we predicted the burden of cancer in Catalonia from 2015 to 2025. METHODS: Bayesian age-period-cohort models were used to predict the burden of cancer from 2015 to 2025 using incidence data from the Girona and Tarragona cancer registries and cancer mortality data from the Catalan mortality registry. Using the Bashir-Estève method, we divided the net change in the number of cases between 2015 and 2025 into changes due to population size (S), cancer risk (R) and age (A) distribution. RESULTS: By 2025, there will be 21,743 new cancer cases in men (40% aged > 74 years) and 17,268 in women (37% aged > 74 years). More than 40% of the new cases will be diagnosed among population aged 74 and older in prostate, colorectal, lung, bladder, pancreatic and stomach cancers in men, and in colorectal, pancreatic and bladder cancers and leukaemia in women. During 2015-2025, the number of new diagnoses will increase by 5.5% in men (A + R + S = 18.1% - 13.3% + 0.7% = 5.5%) and 11.9% in women (A + R + S = 12.4% - 1.1% + 0.6% = 11.9%). Overall cancer mortality rates will continue to decrease during 2015-2025. Lung cancer will be the most lethal cancer among men (N = 2705) and women (N = 1174). CONCLUSIONS: The increase in the number of cancer cases in Catalonia from 2015 to 2025 will mostly affect the elderly, prompting the need for increased collaboration between geriatricians and oncologists.

Assessing predicted age-specific breast cancer mortality rates in 27 European countries by 2020.

BACKGROUND: We assessed differences in predicted breast cancer (BC) mortality rates, across Europe, by 2020, taking into account changes in the time trends of BC mortality rates during the period 2000-2010. METHODS: BC mortality data, for 27 European Union (EU) countries, were extracted from the World Health Organization mortality database. First, we compared BC mortality data between time periods 2000-2004 and 2006-2010 through standardized mortality ratios (SMRs) and carrying out a graphical assessment of the age-specific rates. Second, making use of the base period 2006-2012, we predicted BC mortality rates by 2020. Finally, making use of the SMRs and the predicted data, we identified a clustering of countries, assessing differences in the time trends between the areas defined in this clustering. RESULTS: The clustering approach identified two clusters of countries: the first cluster were countries where BC predicted mortality rates, in 2020, might slightly increase among women aged 69 and older compared with 2010 [Greece (SMR 1.01), Croatia (SMR 1.02), Latvia (SMR 1.15), Poland (SMR 1.14), Estonia (SMR 1.16), Bulgaria (SMR 1.13), Lithuania (SMR 1.03), Romania (SMR 1.13) and Slovakia (SMR 1.06)]. The second cluster was those countries where BC mortality rates level off or decrease in all age groups (remaining countries). However, BC mortality rates between these clusters might diminish and converge to similar figures by 2020. CONCLUSIONS: For the year 2020, our predictions have shown a converging pattern of BC mortality rates between European regions. Reducing disparities, in access to screening and treatment, could have a substantial effect in countries where a non-decreasing trend in age-specific BC mortality rates has been predicted.

Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective.

The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing.

Anti-SSA/Ro52 autoantibodies in scleroderma: results of an observational, cross-sectional study.

OBJECTIVES: To date, the diagnostic utility of anti-SSA/Ro52 autoantibodies in scleroderma and the association of them with certain clinical manifestations, particularly inflammatory myositis, are still controversial. This paper aims to assess the correlation between the presence of anti-SSA/Ro52 antibodies and the demographic, clinical and prognosis characteristics of patients with systemic sclerosis (SSc). METHODS: This is a retrospective, cross-sectional and observational study in patients with SSc. Baseline demographic and clinical characteristics were recorded. Presence of anti-SSA/Ro52, anti-SSA/Ro, anti-SSB/La, snRNP/Sm, anti-centromere, anti-Scl-70 and anti-PM-Scl were analysed by immunoblot, and antinuclear antibodies (ANA) by indirect immunofluorescence. Statistical analysis was performed with PASW Statics 18 software. RESULTS: A total of 132 consecutive patients with analysis of anti-SSA/Ro52 antibodies were selected from a Spanish cohort of 408 patients with SSc, 87.1% of them being women. About half of patients had the limited form (51.5%), followed by diffused form (18.9%), sclerosis sine scleroderma (22.7%), and pre-scleroderma (6.8%). Prevalence of anti-SSA/Ro52 was 35.6%. No association between anti-SSA/Ro52 and clinical manifestations was found, while detection of anti-SSA/Ro52 was significantly associated with the presence of anti-Ro. CONCLUSIONS: The results of our study show that anti-SSA/Ro52 antibodies are often found in SSc patients. No clinical manifestations, including inflammatory myopathy, were related with anti-SSA/Ro antibodies.

Proporción de cáncer de mama en mujeres de 50 a 69 años de Girona según el método de detección / Proportion of breast cancer in women aged 50 to 69 years from Girona, Spain, according to detection method

Fundamento y objetivo: El objetivo de este estudio fue determinar el estadio tumoral, la proporción de casos y la tasa específica por edad de las pacientes con cáncer de mama (CM) según el método de detección. Material y método: Los datos se obtuvieron del Registro de Cáncer de Girona de base poblacional. Se incluyeron las mujeres de 50 a 69 años diagnosticadas de CM en la provincia de Girona durante el período 1999-2006 (n = 1.254). Se clasificaron los CM según el método de detección: cáncer de cribado, cáncer de intervalo y otros. Se calculó la proporción de casos y la tasa específica por edad según el método de detección.Resultados: Durante los años 2002-2006, un 42,2% de los CM diagnosticados en Girona fueron cánceres de cribado, el 52,0% se detectaron fuera del Programa de Detección Precoz del Cáncer de Mama (PDPCM), y el 5,8% fueron cánceres de intervalo. Con la implementación del PDPCM disminuyó la incidencia del CM diagnosticado fuera del programa, aumentó la de los cánceres de cribado y poco después incrementó la de los cánceres de intervalo. Conclusiones: Durante los primeros años del funcionamiento del PDPCM (2002-2006) los casos de cáncer de intervalo representaron un porcentaje bajo (5,8%) respecto el total de CM diagnosticados en mujeres de 50 a 69 años en la provincia de Girona (AU)

Background and objective: The aim of this study was to determine the tumor stage, the proportion of cases and the age specific rate of breast cancer (BC) cases according to detection method. Material and method: Cases of women aged 50 to 69 years diagnosed with BC in the Girona province during 1999-2006 were extracted from the population-based Girona Cancer Registry (n = 1,254). BC was classified by detection method: screen-detected cancer, interval cancer and others. Proportion of cases and age-specific incidence were calculated according to detection method. Results: During the period 2002-2006, the proportion of screen-detected cancers, interval cancers and other cancers were 42.2%, 5.8% and 52.2%, respectively. After implementation of the early detection of breast cancer program (PDPCM), the incidence of screen-detected cases raised; thereafter, interval cancers also increased and the rate of other cancers decreased. Conclusions: In the Girona province during the fully implemented PDPCM period (2002-2006), interval cancers represented a low proportion (5.8%) of women diagnosed with BC at 50 to 69 years old (AU)

[Proportion of breast cancer in women aged 50 to 69 years from Girona, Spain, according to detection method]. / Proporción de cáncer de mama en mujeres de 50 a 69 años de Girona según el método de detección.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the tumor stage, the proportion of cases and the age specific rate of breast cancer (BC) cases according to detection method. MATERIAL AND METHOD: Cases of women aged 50 to 69 years diagnosed with BC in the Girona province during 1999-2006 were extracted from the population-based Girona Cancer Registry (n=1,254). BC was classified by detection method: screen-detected cancer, interval cancer and others. Proportion of cases and age-specific incidence were calculated according to detection method. RESULTS: During the period 2002-2006, the proportion of screen-detected cancers, interval cancers and other cancers were 42.2%, 5.8% and 52.2%, respectively. After implementation of the early detection of breast cancer program (PDPCM), the incidence of screen-detected cases raised; thereafter, interval cancers also increased and the rate of other cancers decreased. CONCLUSIONS: In the Girona province during the fully implemented PDPCM period (2002-2006), interval cancers represented a low proportion (5.8%) of women diagnosed with BC at 50 to 69 years old.

Cancer incidence and mortality projections up to 2020 in Catalonia by means of Bayesian models.

PURPOSE: To predict the burden of cancer in Catalonia by 2020 assessing changes in demography and cancer risk during 2010-2020. METHODS/PATIENTS: Data were obtained from Tarragona and Girona cancer registries and Catalan mortality registry. Population age distribution was obtained from the Catalan Institute of Statistics. Predicted cases in Catalonia were estimated through autoregressive Bayesian age-period-cohort models. RESULTS: There will be diagnosed 26,455 incident cases among men and 18,345 among women during 2020, which means an increase of 22.5 and 24.5 % comparing with the cancer incidence figures of 2010. In men, the increase of cases (22.5 %) can be partitioned in three components: 12 % due to ageing, 8 % due to increase in population size and 2 % due to cancer risk. In women, the role of each component was 9, 8 and 8 %, respectively. The increased risk is mainly expected to be observed in tobacco-related tumours among women and in colorectal and liver cancers among men. During 2010-2020 a mortality decline is expected in both sexes. CONCLUSION: The expected increase of cancer incidence, mainly due to tobacco-related tumours in women and colorectal in men, reinforces the need to strengthen smoking prevention and the expansion of early detection of colorectal cancer in Catalonia.

Anti-ganglioside antibodies in patients with systemic lupus erythematosus and neurological manifestations.

INTRODUCTION: Anti-ganglioside antibodies (AGA) have been associated with several peripheral neuropathies, such as Miller-Fisher syndrome, Guillain-Barré syndrome and multifocal motor neuropathy. They have also been studied in patients with systemic lupus erythematosus (SLE), focusing on neuropsychiatric manifestations and peripheral neuropathy, but the results are contradictory. OBJECTIVE: To study the presence of AGA in a large cohort of patients with SLE and neuropsychiatric manifestations. PATIENTS AND METHODS: Serum from 65 consecutive patients with SLE and neuropsychiatric manifestations, collected from 1985 to 2009, was tested for the presence of AGA antibodies (GM1, GM2, GM3, asialo-GM1 GD1a, GD1b, GD3, GT1b, GQ1b) using a standard enzyme-linked immunosorbent assay ELISA test (INCAT 1999) and thin layer chromatography (TLC). RESULTS: Positive results for asialo-GM1 (IgM) were found in 10 patients, 6 were positive for asialo-GM1 (IgM and IgG), and 4 were positive for other AGA such as GM1, GM2, GM3, GD1b, GT1b, GD3, (mainly IgM). CONCLUSIONS: Clinical and statistical studies showed no correlation between AGA and neuropsychiatric manifestations of SLE. Although some patients showed reactivity to AGA, these antibodies are not a useful marker of neuropsychiatric manifestations in SLE patients.

Effect of using reporting guidelines during peer review on quality of final manuscripts submitted to a biomedical journal: masked randomised trial.

OBJECTIVE: To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts. DESIGN: Masked randomised trial. Population Original research manuscripts submitted to the Medicina Clínica journal from May 2008 to April 2009 and considered suitable for publication. CONTROL GROUP: conventional peer reviews alone. Intervention group: conventional review plus an additional review looking for missing items from reporting guidelines. Outcomes Manuscript quality, assessed with a 5 point Likert scale (primary: overall quality; secondary: average quality of specific items in paper). Main analysis compared groups as allocated, after adjustment for baseline factors (analysis of covariance); sensitivity analysis compared groups as reviewed. Adherence to reviewer suggestions assessed with Likert scale. RESULTS: Of 126 consecutive papers receiving conventional review, 34 were not suitable for publication. The remaining 92 papers were allocated to receive conventional reviews alone (n=41) or additional reviews (n=51). Four papers assigned to the conventional review group deviated from protocol; they received an additional review based on reporting guidelines. We saw an improvement in manuscript quality in favour of the additional review group (comparison as allocated, 0.25, 95% confidence interval -0.05 to 0.54; as reviewed, 0.33, 0.03 to 0.63). More papers with additional reviews than with conventional reviews alone improved from baseline (22 (43%) v eight (20%), difference 23.6% (3.2% to 44.0%), number needed to treat 4.2 (from 2.3 to 31.2), relative risk 2.21 (1.10 to 4.44)). Authors in the additional review group adhered more to suggestions from conventional reviews than to those from additional reviews (average increase 0.43 Likert points (0.19 to 0.67)). CONCLUSIONS: Additional reviews based on reporting guidelines improve manuscript quality, although the observed effect was smaller than hypothesised and not definitively demonstrated. Authors adhere more to suggestions from conventional reviews than to those from additional reviews, showing difficulties in adhering to high methodological standards at the latest research phases. To boost paper quality and impact, authors should be aware of future requirements of reporting guidelines at the very beginning of their study. Trial registration and protocol Although registries do not include trials of peer review, the protocol design was submitted to sponsored research projects (Instituto de Salud Carlos III, PI081903).

Echocardiography at diagnosis of antiphospholipid syndrome provides prognostic information on valvular disease evolution and identifies two subtypes of patients.

The evolution of valvular disease in antiphospholipid syndrome (APS) is barely known. In order to evaluate whether the presence or absence of valvular disease at the time of diagnosis of APS, assessed by an initial echocardiogram, predicts its subsequent evolution, we performed a prospective cohort study. We included 53 patients with APS. An initial transthoracic echocardiogram was performed on patients at the time of diagnosis of APS. Serial echocardiograms were conducted along a 12-year follow-up. Final echocardiograms were used for comparative purposes. We started with 29 patients (54%) with and 24 (45%) without valvulopathy at initial echo. At the final echocardiogram, 27 of 29 patients with initial valvulopathy continued to have valvular disease (a 93% observed likelihood), and 22 of 24 patients without initial valvulopathy demonstrated an absence of valvular disease (a 91% observed likelihood). Patients with valvulopathy in comparison with those without presented more arterial thrombotic events (69% vs. 20%, P < 0.001), atherosclerotic risk factors (62% vs. 29%, P = 0.01), livedo (48% vs. 16%, P = 0.01) and migraine (41% vs. 12%, P = 0.02). We have identified two subtypes of APS patients with and without valvulopathy by defining differential clinical features and with little crossover in valvular involvement over a long follow-up period, giving a high prognostic value to the initial echocardiographic assessment.

Medicina Clínica, un nuevo rumbo / Medicina Clínica, un nuevo rumbo

No disponible

No disponible

Chronic intestinal pseudo-obstruction associated with biliary tract dilatation in a patient with systemic lupus erythematosus.

We present the case of a 57-year old female patient diagnosed with systemic lupus erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo-obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with malignant or litiasic obstruction is reported. The combination of bile duct associated with CIPO in a patient with lupus has not been previously reported in the literature and it probably suggests a smooth muscle dysmotility.

Systemic sclerosis developing in association with the use of interferon alpha therapy for chronic viral hepatitis.

In 1992 interferon alpha (IFNalpha) was approved by the FDA for the treatment of chronic viral hepatitis B and C. Since then IFNalpha has been implicated in the development of several autoantibodies as well as in the development or exacerbation of various autoimmune disorders. Herein, we describe a 47-year-old female who developed a limited form of systemic sclerosis (SSc) with lung involvement 6 months after the institution of IFNalpha therapy for chronic active hepatitis C. There was no family or personal history of autoimmune diseases. We speculate that the immunomodulatory effects of IFNalpha triggered the clinical manifestations of SSc in this patient. To our knowledge, this is the second case of SSc developing after therapy with IFNalpha and the first in a patient treated for chronic viral hepatitis C.

Contribution of the initial features of systemic lupus erythematosus to the clinical evolution and survival of a cohort of Mediterranean patients.

BACKGROUND: Systemic lupus erythematosus has a wide spectrum of immunological and clinical manifestations. Its course is characterised by exacerbations which may result in mortality or morbidity to vital organs/systems. OBJECTIVE: To determine clear and early prognostic markers to avoid further complications. METHODS: 245 adult patients diagnosed between January 1978 and March 2001 were studied. Clinical manifestations and laboratory findings both at onset and during the clinical course were collected. The number, type, and severity of the flares were also noted. Statistical analyses between disease features at onset, subsequent flares, and mortality were performed. RESULTS: 239 patients entered the study. Their mean age at onset was 30 years. The mean time between onset and diagnosis was 36 months and the mean evolution time was 114 months. 205 patients developed 915 flares; 205 (22.4%) of these flares were major flares, and affected 110 patients. Cardiac, neurological, or renal affection at onset were associated with a higher probability of developing cardiac (p=0.022), neurological (p<0.001), and renal (p<0.001) exacerbations, respectively, during the evolution. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) were predictors of stroke (aCL, p=0.000; LA, p=0.001). Age at diagnosis (p=0.003) and valvular disease at onset (p=0.008) were independent predictors of low survival. CONCLUSIONS: Renal, cardiac, or neurological involvement and the presence of LA or aCL positivity at onset were predictors of renal, cardiac, or neurological flares, respectively. Age and valvular involvement at onset were found to be independent adverse outcome predictors for low survival.