RESUMEN
BACKGROUND: A man in his fifties, originally from a Middle Eastern country, presented with left-sided otalgia and neck pain which worsened over several months. He had pre-existing hypertension, diabetes mellitus type 2 and end stage renal disease requiring dialysis. CASE PRESENTATION: His presenting complaints started whilst on a long stay in his country of origin. Symptoms progressively worsened over the coming months while he underwent extensive medical examinations and investigations. This revealed opacifications in the mastoid cavities, raised inflammatory markers, and finally a CT scan revealed osteolytic lesions in his cervical spine. The lesions continued to progress, and his clinical condition deteriorated to the point that he required surgery. Culture was obtained through perioperative biopsies and showed growth of Aspergillus flavus. INTERPRETATION: The patient had initially received topical treatment for an assumed infectious external otitis. Later culture from his outer ear also showed growth of A. flavus, the same pathogen that was found in a biopsy from his cervical spine. He was diagnosed with cervical mycotic osteomyelitis, probably secondary to a chronic external otitis. Long term antimycotic therapy and three neurosurgical operations were required to treat the patient.
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Osteomielitis , Otitis Externa , Vértebras Cervicales , Conducto Auditivo Externo , Humanos , Masculino , Osteomielitis/diagnóstico , Osteomielitis/terapia , Otitis Externa/complicaciones , DolorRESUMEN
Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 × 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
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2',5'-Oligoadenilato Sintetasa/genética , Interferón Tipo I/genética , Sitios de Carácter Cuantitativo/genética , Síndrome de Sjögren/genética , 2',5'-Oligoadenilato Sintetasa/biosíntesis , Alelos , Empalme Alternativo/genética , Femenino , Regulación de la Expresión Génica , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Interferón Tipo I/metabolismo , Masculino , Síndrome de Sjögren/metabolismo , Síndrome de Sjögren/patología , Virosis/genética , Virosis/virologíaRESUMEN
BACKGROUND: Short-term survival after kidney transplantation is excellent, but long-term survival remains low and is equivalent to non-end-stage renal disease patients with many invasive malignancies. The aim of the study was to explore vitamin D status in the early phase after transplantation as a prognostic marker for long-term graft and patient survival. METHODS: All first-time kidney transplant recipients between October 2007 and October 2012 in Norway were included. Vitamin D was measured 10 weeks post-transplant. Information on graft failure and death was obtained from the Norwegian Renal Registry. RESULTS: Seven hundred and sixty-two first-time kidney transplant recipients were included, with a median age of 57 years and a median follow-up of 82 months. In the follow-up period, there were 172 graft failures (23%) and 118 deaths (15%). Eighty-six percent of the transplant recipients with sufficient vitamin D levels were alive with a well-functioning graft after 5 years using Kaplan-Meier survival estimates, compared with 79% and 76% of the patients with vitamin D deficiency and insufficiency, respectively (P = 0.006). CONCLUSION: In a nation-wide cohort of 762 first-time kidney transplant recipients, long-term graft and patient survival were better in recipients with vitamin D sufficiency 10 weeks post-transplant compared with those with vitamin D deficiency and insufficiency.
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Rechazo de Injerto/mortalidad , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias/mortalidad , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Incidencia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de Trasplantes , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Adulto JovenRESUMEN
AIMS: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, -effectiveness, and safety of iron isomaltoside (Monofer®, Pharma-cosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice. MATERIALS AND METHODS: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care. RESULTS: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment. In patients with a baseline Hb < 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb ≥ 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was > 1,000 mg. There were no serious adverse drug reactions. One non-serious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery. CONCLUSION: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.
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Anemia Ferropénica/tratamiento farmacológico , Disacáridos/uso terapéutico , Compuestos Férricos/uso terapéutico , Hematínicos/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Disacáridos/efectos adversos , Femenino , Compuestos Férricos/efectos adversos , Hematínicos/efectos adversos , Hemoglobinas/metabolismo , Humanos , Hierro , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Países Escandinavos y Nórdicos , Resultado del TratamientoRESUMEN
BACKGROUND: Purple urine bag syndrome (PUBS) can occur in cases of bacteriuria with species expressing enzymes capable of converting tryptophan metabolites to red and blue pigments which are excreted in urine, leaving a characteristic purple colour. Risk factors include urinary catheterisation, constipation and chronic kidney disease. Treatment includes catheter replacement, and antibiotics in case of urinary tract infection. CASE PRESENTATION: A man in his 70s with myelodysplastic syndrome, stage 5 chronic kidney disease and chronic indwelling urinary catheterisation due to benign prostatic hyperplasia was admitted for transfusion for symptomatic anaemia. On the second day of hospitalisation, his urine turned purple. There was no sign of transfusion reaction, haemoglobinuria, myoglobinuria or bilirubinuria. Urine cultures were positive for Proteus vulgaris and Enterococcus faecalis, two species associated with PUBS. INTERPRETATION: The constellation was consistent with PUBS. His bacteriuria was considered colonisation not requiring antibiotic treatment. The catheter was replaced and the urine colour returned to normal.
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Bacteriuria/microbiología , Infecciones Relacionadas con Catéteres/microbiología , Catéteres Urinarios/microbiología , Infecciones Urinarias/microbiología , Anciano , Bacteriuria/terapia , Infecciones Relacionadas con Catéteres/terapia , Enterococcus faecalis/aislamiento & purificación , Humanos , Masculino , Proteus vulgaris/aislamiento & purificación , Infecciones Urinarias/terapia , Orina/microbiologíaRESUMEN
Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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Factores Reguladores del Interferón/genética , Lupus Eritematoso Sistémico/genética , beta Carioferinas/genética , Enfermedades Autoinmunes/genética , Teorema de Bayes , Estudios de Casos y Controles , Estudios de Cohortes , Proteínas de Unión al ADN/genética , Haplotipos , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Regiones Promotoras GenéticasRESUMEN
BACKGROUND: The purpose of this study was to investigate whether or not there has been an increase in the number of admissions for exercise-induced rhabdomyolysis at Stavanger University Hospital (SUS) in recent years. MATERIAL AND METHOD: The study is a retrospective review of patients discharged over the period January 2010 to March 2015 with a diagnosis of exercise-induced rhabdomyolysis and with maximum creatine kinase (CK) levels more than ten times the upper reference limit. RESULTS: A total of 33 patients, 21 women and 12 men, with a median age of 28 years (18 - 68), were included in the study. Of the 33 patients, three quarters (25) were admitted in 2014 - 15, compared with eight over the period 2010 - 13. One patient developed kidney failure that required dialysis. The treatment depended more on the attending physician and department than on the patient's clinical condition and CK-level, but this did not seem to affect the rate of complications. INTERPRETATION: The incidence of exercise-induced rhabdomyolysis at SUS increased from autumn 2014, and this coincided with increased media attention and a new exercise trend. We recommend standardising the treatment of exercise-induced rhabdomyolysis, as current treatment recommendations are based on rhabdomyolysis triggered by causes other than exercise.
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Creatina Quinasa/sangre , Ejercicio Físico/fisiología , Entrenamiento de Fuerza/efectos adversos , Rabdomiólisis , Adolescente , Adulto , Anciano , Femenino , Fluidoterapia , Hospitales Universitarios , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Noruega/epidemiología , Admisión del Paciente/estadística & datos numéricos , Esfuerzo Físico , Estudios Retrospectivos , Rabdomiólisis/sangre , Rabdomiólisis/epidemiología , Rabdomiólisis/etiología , Rabdomiólisis/terapia , Adulto JovenRESUMEN
BACKGROUND: The aim of the study was to investigate whether serum levels of intact parathyroid hormone (iPTH) are associated with an increased risk of cardiovascular events, graft loss, or mortality in kidney transplant patients with optimal transplant function. METHODS: From the Norwegian Renal Registry, we identified 522 patients who received a first kidney transplant from 2001 to 2008 with optimal transplant function defined as an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2, more than one yr after transplantation. Cox's proportional hazard models were used to assess the association between iPTH measured 10 wk after transplantation and the composite endpoint. The estimates were adjusted for age, gender, serum calcium, serum phosphate, diabetes mellitus, cardiovascular disease, and time on dialysis prior to transplantation. RESULTS: Median follow-up time was 3.9 yr (interquartile range, IQR: 2.0-6.0 yr). Patients in the third iPTH quartile (9.3-14.4 pM) had the lowest risk for reaching the composite endpoint. Patients in the fourth iPTH quartile (>14.4 pM) had an increased risk compared to those in the third quartile (HR: 2.60, 95% CI: 1.10-6.16, p=0.03). CONCLUSION: In patients with optimal transplant function, iPTH levels are associated with a clinical outcome consisting of cardiovascular events, graft loss, and all-cause mortality.
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Enfermedades Cardiovasculares/sangre , Rechazo de Injerto/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Hormona Paratiroidea/sangre , Complicaciones Posoperatorias , Biomarcadores/sangre , Calcio/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto/fisiología , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Our understanding of the etiology and pathogenesis of neuropsychiatric involvement in primary Sjögren's syndrome (SS) is incomplete. In systemic lupus erythematosus, it has been reported that antibodies directed against N-methyl-D-aspartate receptor subtype NR2 (anti-NR2) interfere with memory and learning function, as well as mood. This has not been investigated in primary SS; however, the present study was undertaken to advance our understanding of neuropsychiatric involvement in this disease. METHODS: Sixty-six patients with primary SS and 66 age- and sex-matched healthy control subjects underwent clinical examination and neuropsychological evaluation. Anti-NR2 antibodies were measured in serum and cerebrospinal fluid. Hippocampus volume was estimated using software extensions to SPM5. RESULTS: Patients with primary SS had smaller hippocampi than healthy subjects (mean ± SD 8.15 ± 0.98 cm(3) versus 8.49 ± 0.88 cm(3); P = 0.01). In patients with primary SS, anti-NR2 antibodies in cerebrospinal fluid were associated with a worse performance in 8 of 10 memory and learning tests, and anti-NR2 antibodies in serum were associated with a worse performance in 6 of those same tests. In addition, a higher proportion of patients with depression than patients without depression had serum anti-NR2 antibody levels above the cutoff value. CONCLUSION: Results of this study indicate that anti-NR2 antibodies may represent one of the pathogenetic mechanisms for cognitive disturbances and mood disorders in patients with primary SS.
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Autoanticuerpos/sangre , Trastornos de la Memoria/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Síndrome de Sjögren/inmunología , Adulto , Anciano , Autoanticuerpos/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/psicologíaRESUMEN
BACKGROUND: Post-transplant diabetes mellitus is one of the most important cardiovascular risk factors after solid organ transplantation. Factors other than hyperglycaemia found in patients post-transplant, affect the level of haemoglobin A1c (HbA1c), and new markers of hyperglycaemia are needed. Our aim was to establish a 95% reference interval for glycated albumin in kidney transplant recipients, and to compare glycated albumin concentrations to the diagnostic criteria for diabetes mellitus post-transplant using oral glucose tolerance test and HbA1c. METHODS: A total of 341 non-diabetic kidney transplant recipients aged ≥18 years who underwent an oral glucose tolerance test at 8 weeks and 1 year after transplantation were included. Glycated albumin was determined by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The 95% reference interval for glycated albumin was 8.2 (90% CI: 7.2-8.5) to 12.8% (90% CI: 12.2-13.5) which is not significantly different from our laboratory's 95% reference interval for persons without diabetes. At both 8 weeks and 1 year after transplantation, 35 patients (10.3%) fulfilled one, two or all three diagnostic criteria for diabetes mellitus. One year after transplantation, eight additional patients had glycated albumin concentration >12.8%. CONCLUSION: Our findings are in accordance with the notion that kidney transplant recipients form glycation end products like normal controls as estimated by glycated albumin and HbA1c. Further studies should address glycated albumin as a supplemental tool for the diagnosis of post-transplant diabetes mellitus in kidney transplant recipients.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Hiperglucemia , Trasplante de Riñón , Albúmina Sérica , Adolescente , Adulto , Humanos , Glucemia/análisis , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiología , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina Glucada , Productos Finales de Glicación Avanzada , Hiperglucemia/diagnóstico , Hiperglucemia/etiología , Trasplante de Riñón/efectos adversos , Albúmina Sérica/químicaRESUMEN
BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines. Higher levels of FGF23 are associated with increased mortality in hemodialysis-patients and in patients with chronic kidney disease (CKD) stage 2-4. The use of active vitamin D and phosphate binders as recommended in international guidelines, may affect the level of FGF23 and thereby clinical outcome. We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 (iFGF23) and intact parathyroid hormone (iPTH) in patients with CKD stage 3b (glomerular filtration rate (GFR) 30-44 ml/min/1.73 m(2)). METHODS: Seven women and 14 men were included, mean age 65.6 ± 12.2 years. They were randomized in a 1:1 ratio to receive one of two treatment sequences. Group-1 (the alphacalcidol-sevelamer carbonate group): alphacalcidol 0.25 µg once daily for two weeks followed by sevelamer carbonate 800 mg TID with meals for two weeks after a two-week washout period. Group-2 (the sevelamer carbonate-alphacalcidol group): vice versa. Nineteen patients completed the study. The 25-hydroxyvitamin D level at baseline was 97.6 ± 25.0 nmol/l. RESULTS: There were no treatment effects on the iFGF23 and iPTH levels overall. In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate (mean 105.8 ± 41.6 vs. 79.1 ± 36.5 pg/ml, p = 0.047 (CI: 0.4-52.9), and the iPTH level was lower (median: 26.5, range: 14.6-55.2 vs. median 36.1, range 13.4-106.9 pg/ml, p = 0.011). In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period. CONCLUSIONS: In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b, the levels of iFGF23 were not significantly different after the two treatments. However, in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate. This may have therapeutic implications on choice of first line therapy. The number of patients is small and this conclusion is in part based on subgroup analysis. It is therefore important that these results are confirmed in larger studies. TRIAL REGISTRATION NUMBER: European Clinical Trial Database (EudraCT) 2010-020415-36 and Clinical Trials.gov NCT01231438.
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Factores de Crecimiento de Fibroblastos/sangre , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/prevención & control , Hormona Paratiroidea/sangre , Poliaminas/administración & dosificación , Insuficiencia Renal Crónica/sangre , Vitamina D/administración & dosificación , Anciano , Biomarcadores/sangre , Quelantes/administración & dosificación , Estudios Cruzados , Quimioterapia Combinada , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Hiperparatiroidismo Secundario/etiología , Masculino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Sevelamer , Resultado del Tratamiento , Vitaminas/administración & dosificaciónRESUMEN
INTRODUCTION: The objective of this study was to compare the prevalence of primary headaches in systemic lupus erythematosus (SLE) versus healthy subjects, and to determine whether headaches in SLE are associated with MRI- or cerebrospinal fluid (CSF) abnormalities. PATIENTS AND METHODS: The case-control study included MRI- and CSF investigations. Headache was classified according to the International Classification of Headache Disorders. Depression and fatigue were measured with Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) respectively. RESULTS: Twenty-four out of 67 SLE patients and 13 out of 67 age- and gender matched healthy subjects had migraine (36% vs 19%, P = 0.03). Nine (13%) SLE patients had migraine with aura vs 4 (6%) in healthy subjects, P = 0.14. The prevalence of tension type headache was equal (60% in patients vs 58% in controls). There was no association between migraine and SLE disease activity, biochemical or immunological markers, cerebral white matter hyperintensities, interleukin-6 in CSF, impairment of the blood-brain barrier, or intrathecal immunoglobulin production. SLE patients had higher BDI- and FSS scores compared with healthy control subjects, and SLE patients with migraine had higher BDI scores than lupus patients without migraine. CONCLUSIONS: Migraine is more prevalent in SLE patients, associated with depression like in the general population, but not associated with disease activity or abnormalities detected on cerebral MRI, in CSF, or any SLE characteristics except from SLE photosensitivity. The inclusion of the migraine item in SLE disease activity instruments remains questionable.
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Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/etiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/patología , Adulto JovenRESUMEN
INTRODUCTION: Chronic kidney disease mineral and bone disorder (CKD-MBD) is common in patients who have undergone kidney transplantation. There is limited information on the extent to which patients with normal renal function after transplantation have persistent disturbances in their mineral metabolism. AIM: The aim of the study is to investigate the prevalence of elevated intact parathyroid hormone (iPTH) levels at least one yr after transplantation in patients living with a first renal transplant with normal transplant function. METHODS: A retrospective, observational study of 607 patients was collected from the Norwegian Renal Registry. Of these, iPTH was recorded for 360 patients. RESULTS: One hundred and eighty-eight patients (52%) had elevated iPTH levels. Twenty-six patients (7%) had iPTH levels >2.5 times the upper limit of normal (ULN). Patients with a pre-emptive transplant were significantly younger than the patients who had received treatment with dialysis (p < 0.0001). The prevalence of iPTH > ULN was significantly higher in patients with a pre-emptive transplant (p = 0.037). CONCLUSIONS: In post-transplant patients with normal transplant function, our data indicate that more than 50% have elevated levels of iPTH more than one yr after transplantation. If elevated iPTH level is associated with mortality in this patient population, it may have major impact on clinical treatment guidelines.
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Fallo Renal Crónico/sangre , Trasplante de Riñón/efectos adversos , Hormona Paratiroidea/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Fibroblast growth factor 23 (FGF23) is a regulator of mineral metabolism, that has been linked to myocardial remodeling including development of left ventricular (LV) hypertrophy and myocardial fibrosis. The aim of this study was to investigate the relationship between intact FGF23 (iFGF23), myocardial infarct size and LV remodeling following a first acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Forty-two consecutive patients with first-time STEMI, single vessel disease, successfully treated with primary percutaneous coronary intervention were included. Cardiac magnetic resonance (CMR) imaging was performed at day 2, 1 week, 2 months and 1 year post MI, and blood samples were drawn at admittance and at the same time points as the CMRs. The cohort was divided according to the presence or not of heart failure post MI. In the total cohort, iFGF23 (mean ± SD) was significantly lower at day 0 (33.7 ± 20.6 pg/ml) and day 2 (31.5 ± 23.4 pg/ml) compared with a reference interval based on 8 healthy adults (43.9 pg/ml ± 19.0 pg/ml). iFGF23 increased to normal levels (55.8 ± 23.4 pg/ml) seven days post MI. In the subset of patients with signs of acute heart failure, FGF23 was higher at all measured timepoints, reaching significantly higher FGF23 levels at 2 months and 1 year following revascularization. CONCLUSION: There was a reduction in iFGF23 levels during the acute phase of MI, with a normalization at seven days following revascularization. During one-year follow-up, there was a gradual increase in iFGF23 levels in patients with heart failure.
RESUMEN
BACKGROUND: To test the hypothesis that neurofilament light (NfL) in CSF is a biomarker of CNS involvement in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), we measured NfL in CSF from 52 patients with lupus and 54 with pSS and explored associations with clinical, structural, immunological and biochemical abnormalities. METHODS: In CSF, we measured NfL, anti-P antibodies, protein S100B and TWEAK by ELISA and anti-NR2 antibodies by electrochemiluminescence. Anti-phospholipid antibodies and routine immunological tests were performed in blood. IgG and albumin were measured in CSF and serum for assessment of the blood-brain barrier function (Q-albumin) and intrathecal IgG production (IgG index). Cerebral MRI and neuropsychological testing were performed. RESULTS: A multivariable regression model showed that increasing CSF anti-NR2 antibody levels were associated with increasing NfL levels in patients with SLE (B 1.27, 95% CI 0.88-1.65, p < 0.001). Age contributed significantly in the model (B 0.04, 95% CI 0.03-0.05, p < 0.001). Similar findings were observed in the pSS group. Adjusted for age and sex, no associations were found between NfL levels and any MRI data. In SLE patients, higher NfL concentrations were associated with impairments in psychomotor speed and motor function, and in pSS with motor dysfunction. These associations remained in multivariable regression models. CONCLUSIONS: Increased concentration of NfL in CSF is a marker of cerebral involvement in patients with SLE and pSS, is strongly associated with the presence of anti-NR2 antibodies, and correlates with cognitive impairment in several domains.
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Lupus Eritematoso Sistémico , Síndrome de Sjögren , Biomarcadores , Encéfalo/diagnóstico por imagen , Humanos , Filamentos Intermedios , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico por imagen , Proteínas de Neurofilamentos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico por imagenRESUMEN
Epidemiological studies indicate a relation between vitamin D status and autoimmune diseases, and in vitro studies demonstrate an effect of 1,25-dihydroxyvitamin D on immune activation. However, the relation between serum levels of 25-hydroxyvitamin D (25(OH)D) and the effect of vitamin D supplementation on serum levels of cytokines are not settled. In the present study interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, intercellular adhesion molecule-1, interferon-gamma, monocyte chemotactic protein-1, and high sensitivity C-reactive protein, were measured in 437 overweight subjects and 324 completed a one year intervention with 40,000 IU vitamin D per week (group DD), 20,000 IU vitamin D per week (group DP), or placebo (group PP). No consistent relations between serum levels of the cytokines and 25(OH)D were found at baseline. In the intervention study, there was no difference in delta values (value at end of study minus value at inclusion) between the three groups regarding the individual cytokines measured, nor was there any indication of a polarization of the T cells towards a Th2 dominant type. In conclusion, we were not able to demonstrate with certainty any significant relation between serum levels of 25(OH)D levels and a number of cytokines and markers of inflammation.
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Colecalciferol/administración & dosificación , Colecalciferol/uso terapéutico , Citocinas/sangre , Suplementos Dietéticos , Inflamación/sangre , Obesidad/sangre , Obesidad/tratamiento farmacológico , Adulto , Anciano , Biomarcadores/sangre , Colecalciferol/efectos adversos , Estudios Transversales , Suplementos Dietéticos/efectos adversos , Femenino , Humanos , Inflamación/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Fumar/sangre , Vitamina D/análogos & derivados , Vitamina D/sangre , Adulto JovenRESUMEN
Interleukin-1beta (IL-1beta) is involved in the regulation of sickness behaviour in response to infection and inflammation in animals. Human fatigue can be considered an element of sickness behaviour and is a prominent and often disabling phenomenon in autoimmune diseases such as primary Sjögren's syndrome (PSS). The role of the IL-1 system in the fatigue of patients with PSS was explored. A cerebrospinal fluid (CSF) analysis of IL-1beta, IL-1Ra, and IL-1sRII was performed in 54 PSS patients and 53 control subjects. Fatigue was evaluated in the patients using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS); mood was evaluated using the Beck Depression Inventory (BDI). There were higher CSF levels of IL-1Ra pg/mL in PSS patients vs. controls (median 38.4: range 15.4-81.7 vs. 33.7: 7.3-163.1, p=0.026). Fatigue VAS scores were associated with increasing CSF levels of IL-1Ra in PSS patients (R(2)=0.11, p=0.015). In a subgroup analysis of the non-depressed PSS patients (N=37; 69%), the association between VAS scores and IL-1Ra was even stronger (R(2)=0.20, p=0.006). The positive association between VAS scores and IL-1Ra remained significant in a multiple regression analysis adjusting for age and BDI scores. Increased levels of IL-1Ra in the CSF are associated with increasing fatigue in PSS patients, indicating that the activated IL-1 system is a possible biological factor associated with fatigue.
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Fatiga/líquido cefalorraquídeo , Proteína Antagonista del Receptor de Interleucina 1/líquido cefalorraquídeo , Receptores Tipo II de Interleucina-1/metabolismo , Síndrome de Sjögren/líquido cefalorraquídeo , Adulto , Anciano , Depresión/líquido cefalorraquídeo , Fatiga/complicaciones , Femenino , Humanos , Conducta de Enfermedad , Mediadores de Inflamación/líquido cefalorraquídeo , Interleucina-1beta/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/complicaciones , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Few studies have focused on patients actually attending renal units for their follow-up over time. This study reports the type of prevalent patients (case-mix) with a renal condition being followed up by 19 renal units in the Nordic countries during 1998-99. MATERIAL AND METHODS: In a joint quality of care development project between the renal societies of the five Nordic countries and the unit for Quality of Health Systems, WHO (Europe), 19 renal units collected data on a random sample of their prevalent patients. RESULTS: At follow-up, 56% had chronic kidney disease (CKD) not in renal replacement therapy (RRT). Seventeen per cent had haemodialysis (HD), 6% peritoneal dialysis (PD) and 21% a functioning kidney transplant (Tx). In the CKD group, 5.9% were CKD stage 1, 17.6% stage 2, 35.2% stage 3, 25.6% stage 4 and 15.7% stage 5. One-third had known cardiovascular disease, 30% known diabetes, half had a blood pressure >140/90 mmHg and 75% > 130/80 mmHg. Twenty eight per cent had left ventricular hypertrophy, 20% were smokers and 17% were anaemic. One-third of those with known cardiovascular disease were prescribed lipid-lowering therapy and half of those with proteinuria were prescribed an angiotensin-inhibiting drug. CONCLUSIONS: The data, collected in 1998-99, indicate that there is room for improvement in the quality of care provided by renal units to patients with CKD. The data may serve as a basis for assessing possible change in nephrological practice after the introduction of K/DOQI guidelines and staging of chronic renal disease.
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Grupos Diagnósticos Relacionados , Enfermedades Renales/terapia , Evaluación de Resultado en la Atención de Salud/normas , Garantía de la Calidad de Atención de Salud/normas , Derivación y Consulta , Adulto , Anciano , Enfermedad Crónica , Dinamarca/epidemiología , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Islandia/epidemiología , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Diálisis Peritoneal , Diálisis Renal , Estudios Retrospectivos , Suecia/epidemiologíaRESUMEN
Primary Sjögren's syndrome (PSS) mainly affects exocrine glands and is clinically characterized by keratoconjunctivitis sicca and xerostomia. Among several possible extraglandular manifestations, involvement of the peripheral nervous system may occur with reported frequencies from 10% to 60%. Peripheral nerve manifestations constitute sensory neuropathy, including sensory ganglioneuronopathy, sensorimotor, including polyradiculoneuropathy and demyelinating neuropathy, motor neuropathy, multiple mononeuropathy, trigeminal and other cranial neuropathies, autonomic neuropathy, and mixed patterns of neuropathy. Knowledge of the neurological manifestations of PSS is hampered by evolving classification criteria of PSS over the years, and by use of highly selected patient populations on the basis of a primary neurological diagnosis. Sural nerve biopsy may show vascular or perivascular inflammation of small epineurial vessels (both arterioles and venules) and in some cases necrotizing vasculitis. Loss of myelinated nerve fibers is common and loss of small diameter nerve fibers occurs. Pathology in cases of sensory ganglioneuronopathy consists of loss of neuronal cell bodies and infiltration of T cells. Peripheral neuropathy in PSS often is refractory to treatment although newer biological agents may provide more effective treatment options. Current treatment strategies used in autoimmune neuropathies may be tried depending upon characteristics of the neuropathy and results obtained by a thorough clinical and laboratory investigation.
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Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Síndrome de Sjögren/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/inmunología , Enfermedades del Sistema Nervioso Autónomo/patología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Quimiotaxis de Leucocito/inmunología , Ganglios Espinales/inmunología , Ganglios Espinales/patología , Ganglios Espinales/fisiopatología , Humanos , Fibras Nerviosas Mielínicas/inmunología , Fibras Nerviosas Mielínicas/patología , Neuronas Aferentes/inmunología , Neuronas Aferentes/patología , Nervios Periféricos/inmunología , Nervios Periféricos/patología , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/patología , Síndrome de Sjögren/complicaciones , Vasculitis/inmunología , Vasculitis/patología , Vasculitis/fisiopatologíaRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is an inflammatory, autoimmune, multiorgan disease often involving the central and peripheral nervous systems. OBJECTIVE: To determine whether there is a selective small-diameter nerve fiber neuropathy in patients with SLE. DESIGN: Cross-sectional study. SETTING: Stavanger University Hospital, Stavanger, Norway. Patients Sixty patients with SLE, aged 43.2 +/- 13.5 years (mean +/- SD). INTERVENTIONS: Skin biopsies, nerve conduction studies, and clinical neurologic examinations. MAIN OUTCOME MEASURES: Density of intraepidermal small-diameter nerve fibers in skin biopsy specimens and large-diameter nerve fiber function as determined by nerve conduction studies and clinical examinations. RESULTS: The mean density of intraepidermal small-diameter nerve fibers in patients with SLE was 7.5 +/- 3.8/mm. Eight patients (13%) had densities below reference values, consistent with small-diameter nerve fiber neuropathy, and results of nerve conduction studies were normal in 6 of them. Eleven patients (18%) had abnormal results of nerve conduction studies, reflecting large-diameter nerve fiber neuropathy, and 4 patients (7%) were classified by an experienced neurologist as having polyneuropathy after the clinical examination. CONCLUSIONS: An abnormal reduction in intraepidermal small-diameter nerve fiber densities is evident in some patients despite normal function of their larger nerve fibers. This adds further support to the theory that a pure small-diameter nerve fiber neuropathy may occur in SLE.