Treatment of Graves’ ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens

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"nombre" => "Óscar" "apellidos" => "Moreno-Pérez" "email" => array:1 [ 0 => "moreno_osc@gva.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "†" "identificador" => "cor1" ] ] ] 2 => array:3 [ "nombre" => "Víctor" "apellidos" => "González Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff1" ] ] ] 3 => array:3 [ "nombre" => "Nieves" "apellidos" => "Arias Mendoza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff1" ] ] ] 4 => array:3 [ "nombre" => "Montserrat" "apellidos" => "Mauri Dot" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff2" ] ] ] 5 => array:3 [ "nombre" => "Rocío" "apellidos" => "Alfayate Guerra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff2" ] ] ] 6 => array:3 [ "nombre" => "Alicia" "apellidos" => "López Macia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff1" ] ] ] 7 => array:3 [ "nombre" => "Antonio" "apellidos" => "Picó Alfonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff1" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Endocrinology Department. Alicante General Universitary Hospital. Alicante. Spain" "etiqueta" => "a" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Hormone Laboratory. Alicante General Universitary Hospital. Alicante. Spain" "etiqueta" => "b" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "†" "correspondencia" => "Dr. O. Moreno Pérez. Departmento de Endocrinología. Hospital General Universitario de Alicante. Pintor Baeza, 12. 03010 Alicante. España." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de la oftalmopatía de graves con metilprednisolona intravenosa a altas dosis: comparación de dos esquemas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 726 "Ancho" => 1987 "Tamanyo" => 109066 ] ] "descripcion" => array:1 [ "en" => "Distribution of the study population between the two treatment arms. Description of the treatment regimens. GO: Graves’ ophthalmopathy." ] ] ] "textoCompleto" => "INTRODUCTIONThe treatment of active moderate-severe Graves’ ophthalmopathy (GO) is based on the administration of high-dose intravenous glucocorticoids (GCiv). Different studies have shown the greater efficacy and safety of GCiv compared with oral prednisone<a class="elsevierStyleCrossRefs" href="#bb0005">1-4</a> and placebo<a class="elsevierStyleCrossRef" href="#bb0025">5</a>. As a result, the latest consensus report published by the European Group on Graves Orbitopathy (EUGOGO)<a class="elsevierStyleCrossRef" href="#bb0030">6</a> recommends as treatment of choice the administration of intravenous methylprednisolone (MTPiv) at doses of under 8 g, with a level I B of evidence and recommendation grade A. However, such therapy is not without complications, and fulminant liver failure may occur, apparently related to the GCiv dose accumulated in each cycle<a class="elsevierStyleCrossRefs" href="#bb0030">6-11</a>.The main objective of the present study is to compare the safety profiles of two different MTPiv dosing regimens. A secondary objective is assessment of the efficacy of the two treatment regimens.MATERIAL AND METHODSWe performed a retrospective descriptive study of patients with GO treated with MTPiv in our center between January 2006 and June 2008.PatientsSequential sampling was made of patients with moderatesevere GO treated in our center. The study included patients between 16-72 years old not previously subjected to immunosuppressor therapy, radiotherapy or eye surgery. We excluded patients with contraindications for MTPiv pulse therapy (heart arrhythmias, unexplained gastric pain, a history of pulmonary tuberculosis, active liver disease, HIV infection, uncontrolled hypertension). The diagnosis was based on the typical clinical characteristics of the disease, evaluating activity and severity according to the criteria established by the EUGOGO in 2008<a class="elsevierStyleCrossRef" href="#bb0030">6</a> (moderate to severe ophthalmopathy being defined by the presence of one or more of the following: palpebral retraction > 2 mm, moderate or severe soft tissue involvement, exophthalmos > 3 mm above normal for the race and sex, and inconstant or constant diplopia; sight-threatening GO like dysthyroid optic neuropathy or corneal rupture).Treatment regimensTwo MTPiv regimens were compared. Regimen A, which is currently used in our center, involves the administration of 6 doses of 0.5 g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv over 12 consecutive weeks<a class="elsevierStyleCrossRef" href="#bb0015">3</a>. Regimen B was used in our center until late 2006, and was based on the administration of four cycles of 15 mg/kg of MTPiv, followed by another four cycles of 7.5 mg/kg (each cycle consisted of two MTPiv infusions on alternate days —Monday and Wednesday— at two-week interval), with a cumulative dose of 90 mg/kg (total administered dose per patient ranged between 4.9-7.4 g) of MTPiv over a period of 16 weeks1 (<a class="elsevierStyleCrossRef" href="#f0005">fig. 1</a>).<elsevierMultimedia ident="f0005"></elsevierMultimedia>Safety evaluationThe blood samples were collected after a 10-hour fasting period, with quantification of the following before and after treatment: blood glucose, liver cytolysis enzymes (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT]) and lipid profile (total cholesterol, LDL-cholesterol, triglycerides), based on the VisUV Coban 711® enzyme-photometric assay; and cholestasis markers (gamma-glutamyl transpeptidase [GGT], alkaline phosphatase [AP]), based on the VisUV Coban 711® kinetic-photometry technique. The determination of anti-TSH receptor antibodies (TRACK) was carried out by Medizym® TRA enzyme immunoanalysis (reference value [vr] < 14 U/l), while antiperoxidase antibodies (antiTPO) were assessed with Axsym Abbott® electro-chemiluminescence (vr < 34 U/ml).Efficacy evaluationAll patients were evaluated by the same endocrinologist before and after treatment. We establish a cutoff point for repeat evaluation of 11 weeks (range, 6-24), to evaluate the primary study objective (safety). Because of such early evaluation, many patients had not yet been re-evaluated by the Service of Ophthalmology. For this reason, clinical improvement was assessed on the basis of subjective perception of both, the patient and the Endocrinologist, registered in the case history. We recorded too the cases of recurrence and the need for additional MTPiv cycles or posterior radiotherapy or eye surgery.Statistical analysisThe study results were analyzed on an intent-to-treat (ITT) basis, using the SPSS version 15.0 statistical package. The quantitative variables were analyzed with the Mann–Whitney U-test. The quantitative variables corresponding to paired samples in turn were analyzed with the Wilcoxon test. The χ2 test was used to evaluate differences between the categorical variables in 2 × 2 contingency tables. Univariate logistic regression analysis was performed to identify the risk factors associated with the absence of treatment response and a greater probability of GO relapse. Statistical significance was considered for p < 0.05.RESULTSTwenty-four patients (17% males and 83% females) with a mean age at the start of treatment of 45.3 ± 14.7 years were included in the study. Of these subjects, one presented euthyroid Graves’ disease (4%; 95% CI, 1-20), two suffered Hashimoto's disease (8%; 95% CI, 2-26), and the rest presented Graves’ disease with hyperthyroidism (88%; 95% CI, 69-96). All patients presenting Graves’ disease with hyperthyroidism received antithyroid therapy, associating radioiodine in 6 cases, surgery in 4, and all 3 therapeutic modalities in one patient. Radioiodine administration preceded the development of GO in 2 patients (in which GO developed 18 and 88 months after treatment), while another 4 patients presented moderate GO at the time of radioiodine therapy. During follow-up after treatment with MTPiv, one patient required metabolic therapy with radioactive iodine to control the thyroid disease.There were no significant differences in baseline characteristics between the 2 groups. All patients receiving dosing regimen B were women, while regimen A included 4 men (<a class="elsevierStyleCrossRef" href="#t0005">table 1</a>).<elsevierMultimedia ident="t0005"></elsevierMultimedia>SafetyMTPiv was well tolerated, with no detection of immediate side effects. Blood pressure remained stable during treatment. No significant differences were seen in the biochemical parameters at baseline or after the administration of both regimens – with the exception of a decrease in GGT concentration with regimen A (<a class="elsevierStyleCrossRef" href="#t0010">table 2</a>). There was no correlation between the cumulative dose of MTPiv and the ASAT/ALAT ratio.<elsevierMultimedia ident="t0010"></elsevierMultimedia>Side effects were recorded in 4 patients (<a class="elsevierStyleCrossRef" href="#t0015">table 3</a>). Two patients of regimen A presented type 2 diabetes mellitus and one of these subjects, previously treated with insulin, was the only patient that needed to suspend the treatment after two cycles due to poor blood glucose control. Two patients (one belonging to each dosing regimen) presented transaminase elevation that did not double the normal value. Two patients showed transaminase elevation to 2-3 times the normal value: the diabetic patient in whom treatment was suspended and who proved positive for hepatitis C virus infection (regimen A), and a second patient who also showed liver cholestasis enzyme elevation with no associated comorbidity (regimen B). There were no significant differences in side effects between the two treatment groups.<elsevierMultimedia ident="t0015"></elsevierMultimedia>EfficacyRepeated assessment of ocular activity following the completion of treatment was carried out after a median of 11 weeks (percentile 25, 8; percentile 75, 16). The cumulative dose in regimen A was 4.5 g of MTPiv. Percentage subjective clinical improvement in regimen A was 92% (11 out of 12 patients; 95% CI, 65-94%). There were 5 recurrences in the group of patients that responded to treatment: 3 (25%) patients required an additional MTPiv cycle; 1 (9%) patient received orbital radiotherapy; and another patient (9%) required decompressive eye surgery in the course of follow-up.The cumulative dose in regimen B was 5.76 g (percentile 25, 5.13; percentile 75, 6.12). In regimen B all patients experienced improvement of the symptoms and ophthalmological signs. However, 7 recurrences were recorded during follow-up: 5 (45%) patients required additional MTPiv cycles, including 2 (18%) patients who received a total of three MTPiv cycles, one of them also required orbital radiotherapy (having previously received 3 MTPiv cycles, with a total MTPiv cumulative dose of 15 g), and 2 (18%) patients were referred for orbital surgery and had received a single MTPiv treatment cycle. Regimen B showed a higher recurrence risk, although without statistical significance (odds ratio [OR] = 2.78; 95% CI, 0.48-16).The univariate logistic regression analysis did not associate success or failure of MTPiv treatment during follow-up to any of the evaluated clinical variables (i.e., age, age over 50 years, sex, severity of GO, duration of the ocular disease, TRACK antibody titer, maximum TRACK titer > 40, TPO titer, maximum TPO titer > 1000, type of treatment prior to thyroid disease, impairment of visual acuity, diplopia prior to treatment).DISCUSSIONThe present study confirms the safety of MTPiv pulse therapy in patients with moderate to severe GO. No serious adverse events were recorded in relation to MTPiv therapy. The percentage of treatment complications was 16%, which is lower than the previously reported in the literature (17-56%<a class="elsevierStyleCrossRefs" href="#bb0005">1,3,4</a>). Maximum liver cytolysis enzyme elevation was recorded between 1.5-3 months after treatment<a class="elsevierStyleCrossRef" href="#bb0005">1</a>. This justifies the early time of re-evaluation of our patients, though stricter laboratory control could have detected a larger number of mild adverse events. In contrast to the work of Kahaly et al<a class="elsevierStyleCrossRef" href="#bb0015">3</a>, where no cytolysis enzyme elevation was recorded in patients treated with a cumulative dose of 4.5 g of MTPiv, in our series there were two cases of enzyme elevation with the same intravenous GC dose: in one patient the elevation was less than twice the upper limit of normal, while in the other patient (with positive hepatitis C serology) the increase was over three times the upper limit of normal.Different studies have shown a relationship between the recorded side effects and an increased cumulative MTPiv dose per cycle<a class="elsevierStyleCrossRefs" href="#bb0005">1,3,4,7</a>. However, in our series no such association was noted, since there were no significant differences in the number of adverse events between the 2 treatment regimens. This may be because the existing evidence suggests that most side effects occur with doses of over 6-8 g of MTPiv per cycle, and we used a maximum dose of 7.4 g. The existence of positive serological findings for hepatotropic viruses has been related to an increased presence of adverse events. In this same line, the only patient in our series with positive hepatitis C carrier status showed increased liver cytolysis enzyme levels, while a woman with markers indicating past hepatitis B virus infection showed no increase in cytolytic parameters. These observations justify the assessment of hepatitis C and B before starting MTPiv therapy in all patients with GO.MTPiv pulse therapy (the sum of two regimens) in our series of patients with moderate GO proved to be effective, with an initial benefit (91%), superior to the reported in earlier studies with MTPiv as monotherapy (60%-77%<a class="elsevierStyleCrossRefs" href="#bb0015">3,5</a>), although involving a relapse rate of 50% in the course of follow-up in our study. The baseline characteristics of our study population were similar to those described in the literature. The greater percentage of immediate benefit obtained in our series could be due to a less strict definition of the re-evaluation criteria. Earlier studies have reported a greater GC treatment response rate among females and in patients under 50 years of age that could be related to lesser severity of the ophthalmopathy<a class="elsevierStyleCrossRef" href="#bb0015">3</a>. These findings could justify the lesser initial response rate with regimen A, which included the four males in our study, although in the present series univariate logistic regression did not demonstrate it. The patients treated with regimen A required fewer additional treatments than those administered regimen B, despite the fact that the cumulative MTPiv dose was higher in the latter treatment group. This observation differs from the findings of other studies comparing intravenous GC regimens with other regimens involving the oral route, where the clinical improvement was related to the dose of GC administered<a class="elsevierStyleCrossRefs" href="#bb0015">3,5</a>.The limitations of the present study include a shorter follow-up of the patients of the regimen A than those given regimen B, which may have been a source of bias on interpreting the recurrence or reactivation data. We were also unable to compare the degree of disease activity objectively by means of the clinical activity scale, since the corresponding scores were not systematically documented in the patient case histories at the time of the evaluation cutoff point. Likewise, we had no data on the percentage of smokers nor on the presence of autoimmune hepatitis markers in all of our patients.In conclusion, the treatment of active moderate-severe GO with MTPiv pulses is safe and effective with cumulative doses of under 8 g. Regimen A appears to involve fewer relapses, with a lesser cumulative corticoid dose (except in very low-weight patients), and it is more suitable to administer." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "xpalclavsec135506" "titulo" => "Key words" ] 1 => array:2 [ "identificador" => "xpalclavsec135505" "titulo" => "Palabras clave" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "INTRODUCTION" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "MATERIAL AND METHODS" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Treatment regimens" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Safety evaluation" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Efficacy evaluation" ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "s0040" "titulo" => "RESULTS" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "s0045" "titulo" => "Safety" ] 1 => array:2 [ "identificador" => "s0050" "titulo" => "Efficacy" ] ] ] 5 => array:2 [ "identificador" => "s0055" "titulo" => "DISCUSSION" ] 6 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2009-01-19" "fechaAceptado" => "2009-03-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec135506" "palabras" => array:5 [ 0 => "Graves’ ophthalmopathy" 1 => "Graves’ disease" 2 => "Methylprednisolone" 3 => "Recurrence" 4 => "Adverse effects" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec135505" "palabras" => array:5 [ 0 => "Oftalmopatía de Graves" 1 => "Enfermedad de Graves" 2 => "Metilprednisolona" 3 => "Recurrencia" 4 => "Efectos secundarios" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "Rationale and objectiveThe treatment of active moderate-severe Graves’ ophthalmopathy (GO) is based on the administration of highdose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens. Material and methodsWe carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderatesevere GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5g/week followed by 6 doses of 0.25g/week, for a cumulative dose of 4.5g of MTPiv (n=13); and regimen B (16 weeks): 4 cycles of 15mg/kg, followed by 4 cycles of 7.5mg/kg, for a cumulative dose of 90mg/kg (range, 4.9-7.4g) (n=11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence). ResultsMild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension – with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p>0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO. ConclusionsThe treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A." ] "es" => array:1 [ "resumen" => "ObjetivoEl tratamiento de la oftalmopatía de Graves (OG) moderadagrave se basa en la administración de corticoides por vía intravenosa. El presente estudio compara la eficacia y la seguridad de dos regímenes de tratamiento intravenoso con metilprednisolona (MTPiv). Material y métodoSe realizó un estudio descriptivo, retrospectivo, con muestreo secuencial de 24 pacientes (el 83% mujeres) que presentaban OG moderadagrave (criterios EUGOGO) y recibieron tratamiento en nuestro centro entre enero de 2006 y junio de 2008. Se utilizaron los dos regímenes siguientes: A (12 semanas), 6 dosis de 0,5g/semana seguidas de 6 dosis de 0,25g/semana, con una dosis acumulada de 4,5g de MTPiv (n=13); B (16 semanas), 4 ciclos de 15mg/kg, seguidos de 4 ciclos de 7,5mg/kg, para una dosis acumulada de 90mg/kg (intervalo, 4,9-7,9g) (n = 11). Se compararon las variables de seguridad (glucemia basal, enzimas de colestasiscitólisis, perfil lipídico) y de eficacia (mejoría clínica y recurrencia). ResultadosSe observó citólisis hepática de leve moderada en 4 pacientes, una de ellas asociada a colestasis moderada y otra a hiperglucemia, que determinaron la suspensión del tratamiento, sin diferencias entre regímenes. Hubo mejoría con el régimen A en el 92% (intervalo de confianza [IC] del 95%, 65-94) frente al 100% con el régimen B (IC del 95%, 74-100). La tasa de recurrencia fue del 43% con el régimen A y el 63% con el B (p>0,05). Ninguna de las variables analizadas en el estudio univariable de regresión logística se asoció a menor respuesta al tratamiento o mayor recurrencia de OG. ConclusionesEl tratamiento de la OG mediante MTPiv es seguro y efectivo, con menor tasa de recurrencia con la dosificación del régimen A." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 726 "Ancho" => 1987 "Tamanyo" => 109066 ] ] "descripcion" => array:1 [ "en" => "Distribution of the study population between the two treatment arms. Description of the treatment regimens. GO: Graves’ ophthalmopathy." ] ] 1 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ALAT: alanine aminotransferase; ASAT: aspartate aminotransferase; AITD: autoimmune thyroid disease; DM: diabetes mellitus; F: female; GGT: gamma-glutamyl transpeptidase; GO: Graves’ oftalmopathy; HCV: hepatitis C virus; LDL: low density lipoproteins; M: male; TPO: antiperoxidase antibodies; TRACK: anti-TSH receptor antibodies. Median (percentile 25-75) and absolute number." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regimen A (n = 13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regimen B (n = 11) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (33-61) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (34-55) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex (M/F) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AITD (hyper/eu/hypothyroidism) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11/0/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10/1/0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 DM, 1 DM + VHC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biochemistry \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pretreatment TRACK (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (4-31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (2-7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pretreatment TPO (U/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">747 (154-1000) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">122 (167-1000) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fasting glucose (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87 (79-149) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 (81-104) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ASAT (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (17-31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (12-22) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALAT (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (16-40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (12-15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GGT (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (15-28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (11-14) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alkaline phosphatase (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87 (65-135) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (52-60) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum cholesterol (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180 (156-213) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">232 (169-262) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL-cholesterol (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120 (110-126) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">157 (109-200) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triglycerides (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86 (70-110) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">125 (56-138) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oftalmologic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Development of GO before treatment (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.5 (1-13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (4-16) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severity (mild/moderate/severe) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/11/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/11/0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab241501.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of the study population" ] ] 2 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ASAT: aspartate aminotransferase; ALAT: alanine aminotransferase; GGT: gamma-glutamyl transpeptidase; LDL: low density lipoproteins. Median (percentile 25-75)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regimen A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regimen B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fasting glucose (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 (85-100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 (83-105) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.88 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ASAT (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (14-41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (12-39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALAT (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (12-21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (11-27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GGT (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (10-18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (12-83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alkaline phosphatase (U/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102 (77-131) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 (54-77) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum cholesterol (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">203 (187-229) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">211 (181-241) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL-cholesterol (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">114 (112-129) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">114 (92-139) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triglycerides (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 (73-137) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">110 (75-126) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.22 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab241500.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Biochemical characteristics following intravenous methylprednisolone treatment" ] ] 3 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Absolute number (percentage with respect to regimens A/B and total population)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regimen A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Regimen B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild transaminase elevation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate transaminase elevation and cholestasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyperglycemia and transaminase elevation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (18%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (17%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab241499.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Side effects observed in relation to intravenous methylprednisolone treatment" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves’ ophthalmopathy: results of a prospective, single-blind, randomized study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Marcocci" 1 => "L. Bartalena" 2 => "M.L. Tanda" 3 => "L. Manetti" 4 => "E. Dell’Unto" 5 => "R. Rocchi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2001" "volumen" => "8" "paginaInicial" => "3562" "paginaFinal" => "3567" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High-dose intravenous corticosteroid therapy for Graves’ ophthalmopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.E. Macchia" 1 => "M. Bagattini" 2 => "G. Lupoli" 3 => "M. Vitale" 4 => "G. Vitale" 5 => "G. Fenzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF03343835" "Revista" => array:6 [ "tituloSerie" => "J Endocrinol Invest" "fecha" => "2001" "volumen" => "24" "paginaInicial" => "152" "paginaFinal" => "158" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11314743" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G.J. Kahaly" 1 => "S. Pitz" 2 => "G. Hommel" 3 => "M. Dittmar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2005-0148" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2005" "volumen" => "90" "paginaInicial" => "5234" "paginaFinal" => "5240" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15998777" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bb0020" "etiqueta" => "4." 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Tratamiento de la oftalmopatía de graves con metilprednisolona intravenosa a altas dosis: comparación de dos esquemas

Ruth Sánchez-Ortigaa, Óscar Moreno-Péreza,†

Corresponding author

moreno_osc@gva.es

Dr. O. Moreno Pérez. Departmento de Endocrinología. Hospital General Universitario de Alicante. Pintor Baeza, 12. 03010 Alicante. España.

, Víctor González Sáncheza, Nieves Arias Mendozaa, Montserrat Mauri Dotb, Rocío Alfayate Guerrab, Alicia López Maciaa, Antonio Picó Alfonsoa

a Endocrinology Department. Alicante General Universitary Hospital. Alicante. Spain

b Hormone Laboratory. Alicante General Universitary Hospital. Alicante. Spain

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at doses of under 8 g&#44; with a level I B of evidence and recommendation grade A&#46; However&#44; such therapy is not without complications&#44; and fulminant liver failure may occur&#44; apparently related to the GCiv dose accumulated in each cycle<a class="elsevierStyleCrossRefs" href="#bb0030"><span class="elsevierStyleSup">6-11</span></a>&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">The main objective of the present study is to compare the safety profiles of two different MTPiv dosing regimens&#46; A secondary objective is assessment of the efficacy of the two treatment regimens&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">MATERIAL AND METHODS</span><p id="p0015" class="elsevierStylePara elsevierViewall">We performed a retrospective descriptive study of patients with GO treated with MTPiv in our center between January 2006 and June 2008&#46;</p><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Patients</span><p id="p0020" class="elsevierStylePara elsevierViewall">Sequential sampling was made of patients with moderatesevere GO treated in our center&#46; The study included patients between 16-72 years old not previously subjected to immunosuppressor therapy&#44; radiotherapy or eye surgery&#46; We excluded patients with contraindications for MTPiv pulse therapy &#40;heart arrhythmias&#44; unexplained gastric pain&#44; a history of pulmonary tuberculosis&#44; active liver disease&#44; HIV infection&#44; uncontrolled hypertension&#41;&#46; The diagnosis was based on the typical clinical characteristics of the disease&#44; evaluating activity and severity according to the criteria established by the EUGOGO in 2008<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> &#40;moderate to severe ophthalmopathy being defined by the presence of one or more of the following&#58; palpebral retraction &#62; 2 mm&#44; moderate or severe soft tissue involvement&#44; exophthalmos &#62; 3 mm above normal for the race and sex&#44; and inconstant or constant diplopia&#59; sight-threatening GO like dysthyroid optic neuropathy or corneal rupture&#41;&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Treatment regimens</span><p id="p0025" class="elsevierStylePara elsevierViewall">Two MTPiv regimens were compared&#46; Regimen A&#44; which is currently used in our center&#44; involves the administration of 6 doses of 0&#46;5 g&#47;week followed by 6 doses of 0&#46;25 g&#47;week&#44; for a cumulative dose of 4&#46;5 g of MTPiv over 12 consecutive weeks<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>&#46; Regimen B was used in our center until late 2006&#44; and was based on the administration of four cycles of 15 mg&#47;kg of MTPiv&#44; followed by another four cycles of 7&#46;5 mg&#47;kg &#40;each cycle consisted of two MTPiv infusions on alternate days &#8212;Monday and Wednesday&#8212; at two-week interval&#41;&#44; with a cumulative dose of 90 mg&#47;kg &#40;total administered dose per patient ranged between 4&#46;9-7&#46;4 g&#41; of MTPiv over a period of 16 weeks1 &#40;<a class="elsevierStyleCrossRef" href="#f0005">fig&#46;&#160;1</a>&#41;&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Safety evaluation</span><p id="p0030" class="elsevierStylePara elsevierViewall">The blood samples were collected after a 10-hour fasting period&#44; with quantification of the following before and after treatment&#58; blood glucose&#44; liver cytolysis enzymes &#40;aspartate aminotransferase &#91;ASAT&#93;&#44; alanine aminotransferase &#91;ALAT&#93;&#41; and lipid profile &#40;total cholesterol&#44; LDL-cholesterol&#44; triglycerides&#41;&#44; based on the VisUV Coban 711&#174; enzyme-photometric assay&#59; and cholestasis markers &#40;gamma-glutamyl transpeptidase &#91;GGT&#93;&#44; alkaline phosphatase &#91;AP&#93;&#41;&#44; based on the VisUV Coban 711&#174; kinetic-photometry technique&#46; The determination of anti-TSH receptor antibodies &#40;TRACK&#41; was carried out by Medizym&#174; TRA enzyme immunoanalysis &#40;reference value &#91;vr&#93; &#60; 14 U&#47;l&#41;&#44; while antiperoxidase antibodies &#40;antiTPO&#41; were assessed with Axsym Abbott&#174; electro-chemiluminescence &#40;vr &#60; 34 U&#47;ml&#41;&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Efficacy evaluation</span><p id="p0035" class="elsevierStylePara elsevierViewall">All patients were evaluated by the same endocrinologist before and after treatment&#46; We establish a cutoff point for repeat evaluation of 11 weeks &#40;range&#44; 6-24&#41;&#44; to evaluate the primary study objective &#40;safety&#41;&#46; Because of such early evaluation&#44; many patients had not yet been re-evaluated by the Service of Ophthalmology&#46; For this reason&#44; clinical improvement was assessed on the basis of subjective perception of both&#44; the patient and the Endocrinologist&#44; registered in the case history&#46; We recorded too the cases of recurrence and the need for additional MTPiv cycles or posterior radiotherapy or eye surgery&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Statistical analysis</span><p id="p0040" class="elsevierStylePara elsevierViewall">The study results were analyzed on an intent-to-treat &#40;ITT&#41; basis&#44; using the SPSS version 15&#46;0 statistical package&#46; The quantitative variables were analyzed with the Mann&#8211;Whitney U-test&#46; The quantitative variables corresponding to paired samples in turn were analyzed with the Wilcoxon test&#46; The &#967;<span class="elsevierStyleSup">2</span> test was used to evaluate differences between the categorical variables in 2 &#215; 2 contingency tables&#46; Univariate logistic regression analysis was performed to identify the risk factors associated with the absence of treatment response and a greater probability of GO relapse&#46; Statistical significance was considered for p &#60; 0&#46;05&#46;</p></span></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">RESULTS</span><p id="p0045" class="elsevierStylePara elsevierViewall">Twenty-four patients &#40;17&#37; males and 83&#37; females&#41; with a mean age at the start of treatment of 45&#46;3 &#177; 14&#46;7 years were included in the study&#46; Of these subjects&#44; one presented euthyroid Graves&#8217; disease &#40;4&#37;&#59; 95&#37; CI&#44; 1-20&#41;&#44; two suffered Hashimoto&#39;s disease &#40;8&#37;&#59; 95&#37; CI&#44; 2-26&#41;&#44; and the rest presented Graves&#8217; disease with hyperthyroidism &#40;88&#37;&#59; 95&#37; CI&#44; 69-96&#41;&#46; All patients presenting Graves&#8217; disease with hyperthyroidism received antithyroid therapy&#44; associating radioiodine in 6 cases&#44; surgery in 4&#44; and all 3 therapeutic modalities in one patient&#46; Radioiodine administration preceded the development of GO in 2 patients &#40;in which GO developed 18 and 88 months after treatment&#41;&#44; while another 4 patients presented moderate GO at the time of radioiodine therapy&#46; During follow-up after treatment with MTPiv&#44; one patient required metabolic therapy with radioactive iodine to control the thyroid disease&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">There were no significant differences in baseline characteristics between the 2 groups&#46; All patients receiving dosing regimen B were women&#44; while regimen A included 4 men &#40;<a class="elsevierStyleCrossRef" href="#t0005">table 1</a>&#41;&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Safety</span><p id="p0055" class="elsevierStylePara elsevierViewall">MTPiv was well tolerated&#44; with no detection of immediate side effects&#46; Blood pressure remained stable during treatment&#46; No significant differences were seen in the biochemical parameters at baseline or after the administration of both regimens &#8211; with the exception of a decrease in GGT concentration with regimen A &#40;<a class="elsevierStyleCrossRef" href="#t0010">table 2</a>&#41;&#46; There was no correlation between the cumulative dose of MTPiv and the ASAT&#47;ALAT ratio&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0060" class="elsevierStylePara elsevierViewall">Side effects were recorded in 4 patients &#40;<a class="elsevierStyleCrossRef" href="#t0015">table 3</a>&#41;&#46; Two patients of regimen A presented type 2 diabetes mellitus and one of these subjects&#44; previously treated with insulin&#44; was the only patient that needed to suspend the treatment after two cycles due to poor blood glucose control&#46; Two patients &#40;one belonging to each dosing regimen&#41; presented transaminase elevation that did not double the normal value&#46; Two patients showed transaminase elevation to 2-3 times the normal value&#58; the diabetic patient in whom treatment was suspended and who proved positive for hepatitis C virus infection &#40;regimen A&#41;&#44; and a second patient who also showed liver cholestasis enzyme elevation with no associated comorbidity &#40;regimen B&#41;&#46; There were no significant differences in side effects between the two treatment groups&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Efficacy</span><p id="p0065" class="elsevierStylePara elsevierViewall">Repeated assessment of ocular activity following the completion of treatment was carried out after a median of 11 weeks &#40;percentile 25&#44; 8&#59; percentile 75&#44; 16&#41;&#46; The cumulative dose in regimen A was 4&#46;5 g of MTPiv&#46; Percentage subjective clinical improvement in regimen A was 92&#37; &#40;11 out of 12 patients&#59; 95&#37; CI&#44; 65-94&#37;&#41;&#46; There were 5 recurrences in the group of patients that responded to treatment&#58; 3 &#40;25&#37;&#41; patients required an additional MTPiv cycle&#59; 1 &#40;9&#37;&#41; patient received orbital radiotherapy&#59; and another patient &#40;9&#37;&#41; required decompressive eye surgery in the course of follow-up&#46;</p><p id="p0070" class="elsevierStylePara elsevierViewall">The cumulative dose in regimen B was 5&#46;76 g &#40;percentile 25&#44; 5&#46;13&#59; percentile 75&#44; 6&#46;12&#41;&#46; In regimen B all patients experienced improvement of the symptoms and ophthalmological signs&#46; However&#44; 7 recurrences were recorded during follow-up&#58; 5 &#40;45&#37;&#41; patients required additional MTPiv cycles&#44; including 2 &#40;18&#37;&#41; patients who received a total of three MTPiv cycles&#44; one of them also required orbital radiotherapy &#40;having previously received 3 MTPiv cycles&#44; with a total MTPiv cumulative dose of 15 g&#41;&#44; and 2 &#40;18&#37;&#41; patients were referred for orbital surgery and had received a single MTPiv treatment cycle&#46; Regimen B showed a higher recurrence risk&#44; although without statistical significance &#40;odds ratio &#91;OR&#93; &#61; 2&#46;78&#59; 95&#37; CI&#44; 0&#46;48-16&#41;&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">The univariate logistic regression analysis did not associate success or failure of MTPiv treatment during follow-up to any of the evaluated clinical variables &#40;i&#46;e&#46;&#44; age&#44; age over 50 years&#44; sex&#44; severity of GO&#44; duration of the ocular disease&#44; TRACK antibody titer&#44; maximum TRACK titer &#62; 40&#44; TPO titer&#44; maximum TPO titer &#62; 1000&#44; type of treatment prior to thyroid disease&#44; impairment of visual acuity&#44; diplopia prior to treatment&#41;&#46;</p></span></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">DISCUSSION</span><p id="p0080" class="elsevierStylePara elsevierViewall">The present study confirms the safety of MTPiv pulse therapy in patients with moderate to severe GO&#46; No serious adverse events were recorded in relation to MTPiv therapy&#46; The percentage of treatment complications was 16&#37;&#44; which is lower than the previously reported in the literature &#40;17-56&#37;<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1&#44;3&#44;4</span></a>&#41;&#46; Maximum liver cytolysis enzyme elevation was recorded between 1&#46;5-3 months after treatment<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a>&#46; This justifies the early time of re-evaluation of our patients&#44; though stricter laboratory control could have detected a larger number of mild adverse events&#46; In contrast to the work of Kahaly et al<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>&#44; where no cytolysis enzyme elevation was recorded in patients treated with a cumulative dose of 4&#46;5 g of MTPiv&#44; in our series there were two cases of enzyme elevation with the same intravenous GC dose&#58; in one patient the elevation was less than twice the upper limit of normal&#44; while in the other patient &#40;with positive hepatitis C serology&#41; the increase was over three times the upper limit of normal&#46;</p><p id="p0085" class="elsevierStylePara elsevierViewall">Different studies have shown a relationship between the recorded side effects and an increased cumulative MTPiv dose per cycle<a class="elsevierStyleCrossRefs" href="#bb0005"><span class="elsevierStyleSup">1&#44;3&#44;4&#44;7</span></a>&#46; However&#44; in our series no such association was noted&#44; since there were no significant differences in the number of adverse events between the 2 treatment regimens&#46; This may be because the existing evidence suggests that most side effects occur with doses of over 6-8 g of MTPiv per cycle&#44; and we used a maximum dose of 7&#46;4 g&#46; The existence of positive serological findings for hepatotropic viruses has been related to an increased presence of adverse events&#46; In this same line&#44; the only patient in our series with positive hepatitis C carrier status showed increased liver cytolysis enzyme levels&#44; while a woman with markers indicating past hepatitis B virus infection showed no increase in cytolytic parameters&#46; These observations justify the assessment of hepatitis C and B before starting MTPiv therapy in all patients with GO&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall">MTPiv pulse therapy &#40;the sum of two regimens&#41; in our series of patients with moderate GO proved to be effective&#44; with an initial benefit &#40;91&#37;&#41;&#44; superior to the reported in earlier studies with MTPiv as monotherapy &#40;60&#37;-77&#37;<a class="elsevierStyleCrossRefs" href="#bb0015"><span class="elsevierStyleSup">3&#44;5</span></a>&#41;&#44; although involving a relapse rate of 50&#37; in the course of follow-up in our study&#46; The baseline characteristics of our study population were similar to those described in the literature&#46; The greater percentage of immediate benefit obtained in our series could be due to a less strict definition of the re-evaluation criteria&#46; Earlier studies have reported a greater GC treatment response rate among females and in patients under 50 years of age that could be related to lesser severity of the ophthalmopathy<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a>&#46; These findings could justify the lesser initial response rate with regimen A&#44; which included the four males in our study&#44; although in the present series univariate logistic regression did not demonstrate it&#46; The patients treated with regimen A required fewer additional treatments than those administered regimen B&#44; despite the fact that the cumulative MTPiv dose was higher in the latter treatment group&#46; This observation differs from the findings of other studies comparing intravenous GC regimens with other regimens involving the oral route&#44; where the clinical improvement was related to the dose of GC administered<a class="elsevierStyleCrossRefs" href="#bb0015"><span class="elsevierStyleSup">3&#44;5</span></a>&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">The limitations of the present study include a shorter follow-up of the patients of the regimen A than those given regimen B&#44; which may have been a source of bias on interpreting the recurrence or reactivation data&#46; We were also unable to compare the degree of disease activity objectively by means of the clinical activity scale&#44; since the corresponding scores were not systematically documented in the patient case histories at the time of the evaluation cutoff point&#46; Likewise&#44; we had no data on the percentage of smokers nor on the presence of autoimmune hepatitis markers in all of our patients&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; the treatment of active moderate-severe GO with MTPiv pulses is safe and effective with cumulative doses of under 8 g&#46; Regimen A appears to involve fewer relapses&#44; with a lesser cumulative corticoid dose &#40;except in very low-weight patients&#41;&#44; and it is more suitable to administer&#46;</p></span></span>"
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              "titulo" => "Safety"
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            0 => "Graves&#8217; ophthalmopathy"
            1 => "Graves&#8217; disease"
            2 => "Methylprednisolone"
            3 => "Recurrence"
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            0 => "Oftalmopat&#237;a de Graves"
            1 => "Enfermedad de Graves"
            2 => "Metilprednisolona"
            3 => "Recurrencia"
            4 => "Efectos secundarios"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Rationale and objective</span><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">The treatment of active moderate-severe Graves&#8217; ophthalmopathy &#40;GO&#41; is based on the administration of highdose intravenous glucocorticoids&#46; The present study compares the efficacy and safety of 2 different intravenous methylprednisolone &#40;MTPiv&#41; dosing regimens&#46;</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">We carry a retrospective descriptive study with sequential sampling of 24 patients &#40;83&#37; females&#41; presenting moderatesevere GO &#40;EUGOGO criteria&#41; and receiving treatment in our center between January 2006 and June 2008&#46; We use 2 dosing regimens&#58; regimen A &#40;12 weeks&#41;&#58; 6 doses of 0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;week followed by 6 doses of 0&#46;25<span class="elsevierStyleHsp" style=""></span>g&#47;week&#44; for a cumulative dose of 4&#46;5<span class="elsevierStyleHsp" style=""></span>g of MTPiv &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#59; and regimen B &#40;16 weeks&#41;&#58; 4 cycles of 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; followed by 4 cycles of 7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; for a cumulative dose of 90<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;range&#44; 4&#46;9-7&#46;4<span class="elsevierStyleHsp" style=""></span>g&#41; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#46; Comparisons were made for safety &#40;fasting glucose&#44; cytolysis-cholestasis enzymes&#44; lipid profile&#41; and efficacy data &#40;clinical improvement and recurrence&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Mild-moderate liver cytolysis was recorded in four patients&#44; one with associated moderate cholestasis and another with hyperglycemia&#44; leading to treatment suspension &#8211; with no differences between the 2 treatment regimens&#46; Percentage clinical improvement with regimen A was 92&#37; &#40;CI&#44; 65-94&#37;&#41; versus 100&#37; with regimen B &#40;CI&#44; 74-100&#37;&#41;&#46; The recurrence rate was 43&#37; with regimen A and 63&#37; with regimen B &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">The treatment of GO with MTPiv is safe and effective&#44; with a lower recurrence rate when using dosing regimen A&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">El tratamiento de la oftalmopat&#237;a de Graves &#40;OG&#41; moderadagrave se basa en la administraci&#243;n de corticoides por v&#237;a intravenosa&#46; El presente estudio compara la eficacia y la seguridad de dos reg&#237;menes de tratamiento intravenoso con metilprednisolona &#40;MTPiv&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todo</span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio descriptivo&#44; retrospectivo&#44; con muestreo secuencial de 24 pacientes &#40;el 83&#37; mujeres&#41; que presentaban OG moderadagrave &#40;criterios EUGOGO&#41; y recibieron tratamiento en nuestro centro entre enero de 2006 y junio de 2008&#46; Se utilizaron los dos reg&#237;menes siguientes&#58; A &#40;12 semanas&#41;&#44; 6 dosis de 0&#44;5<span class="elsevierStyleHsp" style=""></span>g&#47;semana seguidas de 6 dosis de 0&#44;25<span class="elsevierStyleHsp" style=""></span>g&#47;semana&#44; con una dosis acumulada de 4&#44;5<span class="elsevierStyleHsp" style=""></span>g de MTPiv &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#59; B &#40;16 semanas&#41;&#44; 4 ciclos de 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; seguidos de 4 ciclos de 7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; para una dosis acumulada de 90<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;intervalo&#44; 4&#44;9-7&#44;9<span class="elsevierStyleHsp" style=""></span>g&#41; &#40;n &#61; 11&#41;&#46; Se compararon las variables de seguridad &#40;glucemia basal&#44; enzimas de colestasiscit&#243;lisis&#44; perfil lip&#237;dico&#41; y de eficacia &#40;mejor&#237;a cl&#237;nica y recurrencia&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; cit&#243;lisis hep&#225;tica de leve moderada en 4 pacientes&#44; una de ellas asociada a colestasis moderada y otra a hiperglucemia&#44; que determinaron la suspensi&#243;n del tratamiento&#44; sin diferencias entre reg&#237;menes&#46; Hubo mejor&#237;a con el r&#233;gimen A en el 92&#37; &#40;intervalo de confianza &#91;IC&#93; del 95&#37;&#44; 65-94&#41; frente al 100&#37; con el r&#233;gimen B &#40;IC del 95&#37;&#44; 74-100&#41;&#46; La tasa de recurrencia fue del 43&#37; con el r&#233;gimen A y el 63&#37; con el B &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Ninguna de las variables analizadas en el estudio univariable de regresi&#243;n log&#237;stica se asoci&#243; a menor respuesta al tratamiento o mayor recurrencia de OG&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">El tratamiento de la OG mediante MTPiv es seguro y efectivo&#44; con menor tasa de recurrencia con la dosificaci&#243;n del r&#233;gimen A&#46;</p>"
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of the study population between the two treatment arms&#46; Description of the treatment regimens&#46; GO&#58; Graves&#8217; ophthalmopathy&#46;</p>"
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          "leyenda" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">ALAT&#58; alanine aminotransferase&#59; ASAT&#58; aspartate aminotransferase&#59; AITD&#58; autoimmune thyroid disease&#59; DM&#58; diabetes mellitus&#59; F&#58; female&#59; GGT&#58; gamma-glutamyl transpeptidase&#59; GO&#58; Graves&#8217; oftalmopathy&#59; HCV&#58; hepatitis C virus&#59; LDL&#58; low density lipoproteins&#59; M&#58; male&#59; TPO&#58; antiperoxidase antibodies&#59; TRACK&#58; anti-TSH receptor antibodies&#46; Median &#40;percentile 25-75&#41; and absolute number&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regimen A &#40;n &#61; 13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">53 &#40;34-55&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sex &#40;M&#47;F&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#47;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">0&#47;11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>AITD &#40;hyper&#47;eu&#47;hypothyroidism&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#47;0&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#47;1&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">1 DM&#44; 1 DM &#43; VHC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemistry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pretreatment TRACK &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;4-31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;2-7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pretreatment TPO &#40;U&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">747 &#40;154-1000&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">122 &#40;167-1000&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fasting glucose &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87 &#40;79-149&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96 &#40;81-104&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ASAT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;17-31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;12-22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ALAT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;16-40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;12-15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>GGT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;15-28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;11-14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alkaline phosphatase &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87 &#40;65-135&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;52-60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Serum cholesterol &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180 &#40;156-213&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">232 &#40;169-262&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>LDL-cholesterol &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120 &#40;110-126&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">157 &#40;109-200&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Triglycerides &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86 &#40;70-110&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">125 &#40;56-138&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oftalmologic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Development of GO before treatment &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;5 &#40;1-13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;4-16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Severity &#40;mild&#47;moderate&#47;severe&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;11&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;11&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">ASAT&#58; aspartate aminotransferase&#59; ALAT&#58; alanine aminotransferase&#59; GGT&#58; gamma-glutamyl transpeptidase&#59; LDL&#58; low density lipoproteins&#46; Median &#40;percentile 25-75&#41;&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regimen A&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regimen B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fasting glucose &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;85-100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96 &#40;83-105&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASAT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;14-41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;12-39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALAT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;12-21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;11-27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GGT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;10-18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;12-83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alkaline phosphatase &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102 &#40;77-131&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;54-77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serum cholesterol &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">203 &#40;187-229&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">211 &#40;181-241&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LDL-cholesterol &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">114 &#40;112-129&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">114 &#40;92-139&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Triglycerides &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;73-137&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">110 &#40;75-126&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab241500.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Biochemical characteristics following intravenous methylprednisolone treatment</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "t0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Absolute number &#40;percentage with respect to regimens A&#47;B and total population&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regimen A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regimen B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild transaminase elevation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate transaminase elevation and cholestasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyperglycemia and transaminase elevation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab241499.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Side effects observed in relation to intravenous methylprednisolone treatment</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bs0005"
          "bibliografiaReferencia" => array:11 [
            0 => array:3 [
              "identificador" => "bb0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves&#8217; ophthalmopathy&#58; results of a prospective&#44; single-blind&#44; randomized study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Marcocci"
                            1 => "L&#46; Bartalena"
                            2 => "M&#46;L&#46; Tanda"
                            3 => "L&#46; Manetti"
                            4 => "E&#46; Dell&#8217;Unto"
                            5 => "R&#46; Rocchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2001"
                        "volumen" => "8"
                        "paginaInicial" => "3562"
                        "paginaFinal" => "3567"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bb0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High-dose intravenous corticosteroid therapy for Graves&#8217; ophthalmopathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;E&#46; Macchia"
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Article information

ISSN: 15750922
Original language: English

DOI:10.1016/S1575-0922(09)70841-1

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Year/Month	Html	Pdf	Total

2024 November	2	1	3
2024 October	127	13	140
2024 September	131	14	145
2024 August	126	10	136
2024 July	173	14	187
2024 June	158	9	167
2024 May	142	15	157
2024 April	131	15	146
2024 March	171	9	180
2024 February	167	15	182
2024 January	166	11	177
2023 December	137	15	152
2023 November	137	10	147
2023 October	211	13	224
2023 September	146	4	150
2023 August	104	4	108
2023 July	102	6	108
2023 June	110	8	118
2023 May	131	3	134
2023 April	74	5	79
2023 March	112	8	120
2023 February	74	9	83
2023 January	101	4	105
2022 December	90	13	103
2022 November	125	15	140
2022 October	122	19	141
2022 September	99	29	128
2022 August	107	10	117
2022 July	101	9	110
2022 June	85	14	99
2022 May	85	5	90
2022 April	96	20	116
2022 March	105	20	125
2022 February	108	12	120
2022 January	107	33	140
2021 December	87	21	108
2021 November	110	15	125
2021 October	97	23	120
2021 September	100	20	120
2021 August	109	10	119
2021 July	95	10	105
2021 June	64	11	75
2021 May	81	10	91
2021 April	247	33	280
2021 March	138	5	143
2021 February	94	7	101
2021 January	88	11	99
2020 December	75	8	83
2020 November	66	15	81
2020 October	61	11	72
2020 September	70	19	89
2020 August	58	13	71
2020 July	40	19	59
2020 June	24	7	31
2020 May	42	7	49
2020 April	42	13	55
2020 March	50	11	61
2020 February	247	15	262
2020 January	52	8	60
2019 December	60	9	69
2019 November	45	12	57
2019 October	40	9	49
2019 September	67	13	80
2019 August	30	6	36
2019 July	47	20	67
2019 June	84	14	98
2019 May	219	19	238
2019 April	98	12	110
2019 March	30	4	34
2019 February	23	4	27
2019 January	24	4	28
2018 December	23	1	24
2018 November	20	6	26
2018 October	34	4	38
2018 September	28	10	38
2018 August	22	2	24
2018 July	13	3	16
2018 June	8	2	10
2018 May	17	9	26
2018 April	18	0	18
2018 March	13	0	13
2018 February	11	3	14
2018 January	13	3	16
2017 December	13	3	16
2017 November	21	5	26
2017 October	23	8	31
2017 September	21	8	29
2017 August	21	7	28
2017 July	17	4	21
2017 June	27	29	56
2017 May	39	2	41
2017 April	34	2	36
2017 March	34	1	35
2017 February	36	2	38
2017 January	24	2	26
2016 December	36	2	38
2016 November	41	12	53
2016 October	70	2	72
2016 September	59	6	65
2016 August	32	8	40
2016 July	29	4	33
2016 June	43	10	53
2016 May	31	18	49
2016 April	26	7	33
2016 March	32	11	43
2016 February	28	11	39
2016 January	28	13	41
2015 December	38	18	56
2015 November	36	12	48
2015 October	38	14	52
2015 September	40	12	52
2015 August	27	9	36
2015 July	25	2	27
2015 June	15	6	21
2015 May	46	10	56
2015 April	38	20	58
2015 March	42	13	55
2015 February	24	12	36
2015 January	37	2	39
2014 December	51	11	62
2014 November	40	4	44
2014 October	56	6	62
2014 September	42	2	44
2014 August	50	4	54
2014 July	59	2	61
2014 June	51	7	58
2014 May	32	3	35
2014 April	45	5	50
2014 March	44	2	46
2014 February	51	4	55
2014 January	54	4	58
2013 December	41	4	45
2013 November	39	4	43
2013 October	52	5	57
2013 September	30	11	41
2013 August	48	18	66
2013 July	41	2	43
2009 March	1678	0	1678

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