Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study.

BACKGROUND: Dengue is endemic in many countries throughout the tropics and subtropics, and the disease causes substantial morbidity and health-care burdens in these regions. We previously compared antibody responses after one-dose, two-dose, or three-dose primary regimens with the only approved dengue vaccine CYD-TDV (Dengvaxia; Sanofi Pasteur, Lyon, France) in individuals aged 9 years and older with previous dengue exposure. In this study, we assessed the need for a CYD-TDV booster after these primary vaccination regimens. METHODS: In this randomised, controlled, phase 2, non-inferiority study, healthy individuals aged 9-50 years recruited from three sites in Colombia and three sites in the Philippines (excluding those with the usual contraindications to vaccinations) were randomly assigned 1:1:1 via a permuted block method with stratification by site and by age group using an independent voice response system to receive, at 6-month intervals, three doses of CYD-TDV (three-dose group), one dose of placebo followed by two doses of CYD-TDV (two-dose group), or two doses of placebo followed by one dose of CYD-TDV (one-dose group). Participants were also randomly assigned (1:1) to receive a CYD-TDV booster at 1 year or 2 years after the last primary dose. Each CYD-TDV dose was 0·5 mL and administered subcutaneously in the deltoid region of the upper arm. The investigators and sponsor, study staff interacting with the investigators, and participants and their parents or legally acceptable representatives were masked to group assignment. Neutralising antibodies were measured by 50% plaque reduction neutralisation testing, and geometric mean titres (GMTs) were calculated. Due to a change in study protocol, only participants who were dengue seropositive at baseline in the Colombian cohort received a booster vaccination. The primary outcome was to show non-inferiority of the booster dose administered at 1 year or 2 years after the two-dose and three-dose primary regimens; non-inferiority was shown if the lower limit of the two-sided adjusted 95% CI of the between-group (day 28 post-booster dose GMT from the three-dose or two-dose group vs day 28 GMT post-dose three of the three-dose primary regimen [three-dose group]) geometric mean ratio (GMR) was higher than 0·5 for each serotype. Non-inferiority of the 1-year or 2-year booster was shown if all four serotypes achieved non-inferiority. Safety was assessed among all participants who received the booster. This trial is registered with ClinicalTrials.gov, NCT02628444, and is closed to accrual. FINDINGS: Between May 2 and Sept 16, 2016, we recruited and enrolled 1050 individuals who received either vaccine or placebo. Of the 350, 348, and 352 individuals randomly assigned to three-dose, two-dose, and one-dose groups, respectively, 108, 115, and 115 from the Colombian cohort were dengue seropositive at baseline and received a booster; 55 and 53 in the three-dose group received a booster after 1 year and 2 years, respectively, as did 59 and 56 in the two-dose group, and 62 and 53 in the one-dose group. After the three-dose primary schedule, non-inferiority was shown for serotypes 2 (GMR 0·746; 95% CI 0·550-1·010) and 3 (1·040; 0·686-1·570) but not serotypes 1 (0·567; 0·399-0·805) and 4 (0·647; 0·434-0·963) for the 1-year booster, and again for serotypes 2 (0·871; 0·673-1·130) and 3 (1·150; 0·887-1·490) but not serotypes 1 (0·688; 0·479-0·989) and 4 (0·655; 0·471-0·911) for the 2-year booster. Similarly, after the two-dose primary schedule, non-inferiority was shown for serotypes 2 (0·809; 0·505-1·300) and 3 (1·19; 0·732-1·940) but not serotypes 1 (0·627; 0·342-1·150) and 4 (0·499; 0·331-0·754) for the 1-year booster, and for serotype 3 (0·911; 0·573-1·450) but not serotypes 1 (0·889; 0·462-1·710), 2 (0·677; 0·402-1·140), and 4 (0·702; 0·447-1·100) for the 2-year booster. Thus, non-inferiority of the 1-year or 2-year booster was not shown after the three-dose or two-dose primary vaccination regimen in dengue-seropositive participants. No safety concerns occurred with the 1-year or 2-year CYD-TDV booster. INTERPRETATION: CYD-TDV booster 1 year or 2 years after the two-dose or three-dose primary vaccination regimen does not elicit a consistent, meaningful booster effect against all dengue serotypes in participants who are seropositive for dengue at baseline. FUNDING: Sanofi Pasteur. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America.

BACKGROUND: CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57). METHODS: The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to 5 years after the last injection. RESULTS: In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12-.30] and .15 [.06-.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups. CONCLUSIONS: CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year-olds. Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.

ENECOVID: una experiencia de mejora profesional / ENECOVID: An experience of profesional improvement

En el Centro de Salud El Doctoral, perteneciente al Área de Salud de Gran Canaria, seis enfermeras de Atención Primaria fueron las encargadas de atender a los requerimientos de las 133 familias que participaron en el Estudio Nacional de Seroprevalencia (ENECOVID) dirigido por el Instituto de Salud Carlos III y el Ministerio de Sanidad. En las tres fases del estudio comentadas en este trabajo se atendieron un total de 702 participantes. En la primera fase se valoró a un total de 203 personas, 251 en la segunda y 248 en la tercera fase. Los participantes en su mayoría fueron adultos, siendo el número total de niños atendidos 84. La participación por sexos fue igual (50% hombres y 50% mujeres). Para dar una respuesta adecuada al estudio, dentro del centro, se creó un circuito con puntos de entrada, espera e información a los participantes, donde se les explicaba el objetivo y la dinámica del mismo, y formalizaban el consentimiento informado antes de acceder a las consultas destinadas a su desarrollo. La experiencia de las enfermeras en la investigación ENECOVID redundó en la cohesión del grupo de trabajo, mejoró la destreza en el manejo del paciente con infección por SARS-CoV-2, aumentó la seguridad a la hora de utilizar los equipos de protección individual y repercutió en la capacidad de abordar un gran volumen de participantes sin mermar la calidad de los cuidados.(AU)

At the Doctoral Health Centre, belonging to the Gran Canaria Healthcare Area, six Primary Care nurses were in charge of meeting the requirements of the 133 families included in the National Seroprevalence Study (ENECOVID) conducted by the Instituto de Salud Carlos III and the Ministry of Health. During the three stages of the study discussed in this article, 702 participants were managed in total. In the first stage, 203 persons were evaluated, 251 in the second, and 248 in the third stage. The majority of participants were adult, and the total number of children included was 84. There was equal participation by gender (50% men and 50% women). In order to provide an adequate response to the study, a circuit was created within the centre, with entry, waiting, and information points for participants, where the objective and the dynamics of the study were explained to them, and they completed their informed consent forms before having access to the relevant consultations. The experience of nurses in the ENECOVID research resulted in the cohesion of the work team, improved the skills regarding the management of patients infected with SARS-CoV-2, increased safety at the time of using individual protection equipment, and had a positive impact on the ability to address a great volume of participants without reducing the quality of care.(AU)

Immunogenicity and safety of simplified vaccination schedules for the CYD-TDV dengue vaccine in healthy individuals aged 9-50 years (CYD65): a randomised, controlled, phase 2, non-inferiority study.

BACKGROUND: Three doses of the licensed tetravalent dengue vaccine CYD-TDV (Dengvaxia, Sanofi Pasteur, Lyon France) are immunogenic and effective against symptomatic dengue in individuals aged 9 years and older who are dengue seropositive. Previous trials have provided some evidence that antibody responses elicited after just one dose or two doses of CYD-TDV might be similar to those elicited after three doses. We compared antibody responses following one-dose, two-dose, and three-dose vaccination regimens in individuals who were dengue seropositive at baseline up to 1 year after the last injection. METHODS: In this randomised, controlled, phase 2, non-inferiority study (CYD65), healthy individuals aged 9-50 years were recruited from the community in three sites in Colombia and three sites in the Philippines. Participants were randomly assigned (1:1:1), using a permuted block method with stratification by site and age group, to receive, at 6-month intervals (on day 0, month 6, and month 12), three doses of CYD-TDV (three-dose group), one dose of placebo (on day 0) and two doses of CYD-TDV (at months 6 and 12; two-dose group), or two doses of placebo (on day 0 and month 6) and one dose of CYD-TDV (at month 12; one-dose group). Each dose of CYD-TDV was 0·5 mL, administered subcutaneously into the deltoid of the upper arm. Participants, study staff, investigators, and the funder were masked to group assignment. The co-primary endpoints were geometric mean titres (GMTs) of neutralising antibodies against each dengue virus serotype at 28 days and 1 year after the last vaccine injection. After a protocol amendment during the conduct of the study, the original co-primary objectives of non-inferiority of the one-dose and two-dose groups to the three-dose group were altered to include non-inferiority of the two-dose group to the three-dose group only, to be assessed in individuals who were dengue seropositive at baseline. Non-inferiority was shown if the lower limit of the 95% CI for the ratio of GMTs (GMR) at 28 days and 1 year between groups was more than 0·5 for each serotype. The analysis of the coprimary objectives was done in the per-protocol analysis dataset, which included all participants who had been vaccinated, had no protocol deviations, and had a valid serology test result for at least one dengue serotype at 28 days after the third injection. Safety was assessed throughout in all participants who received at least one injection of study drug, regardless of serostatus. This trial is registered with ClinicalTrials.gov, NCT02628444, and is closed to accrual. FINDINGS: Between May 2, 2016, and Sept 16, 2016, we recruited and enrolled 1050 individuals, of whom 1048 received at least one injection and 993 had at least one blood sample taken (full-analysis dataset; 333 in three-dose group, 328 in two-dose group, and 332 in one-dose group). 860 (86·6%) of 993 participants in the full-analysis dataset were dengue seropositive at baseline. Non-inferiority (two dose vs three dose) was shown for each serotype at both 28 days and 1 year among dengue-seropositive participants (number of participants assessed: 272 [two-dose group], 265 [three-dose group] at 28 days; and 190 [two-dose group], 185 [three-dose group] at 1 year). At 28 days after the last injection, neutralising antibody GMTs were 899 (95% CI 752-1075) in the two-dose group versus 822 (700-964) in the three dose group against dengue serotype 1 (GMR 1·09 [95% CI 0·86-1·39]); 869 (754-1002) versus 875 (770-995) against serotype 2 (GMR 0·99 [0·82-1·20]); 599 (524-685) versus 610 (535-694) against serotype 3 (GMR 0·98 [0·82-1·18]); and 510 (453-575) versus 531 (470-601) against serotype 4 (GMR 0·96 [0·81-1·14]). At year 1, GMTs had decreased but remained above baseline for all serotypes: 504 (95% CI 403-630) in the two-dose group versus 490 (398-604) in the three-dose group against serotype 1 (GMR 1·03 [0·76-1·40]); 737 (611-888) versus 821 (704-957) against serotype 2 (GMR 0·90 [0·71-1·14]); 437 (368-519) versus 477 (405-561) against serotype 3 (GMR 0·92 [0·72-1·16]); and 238 (205-277) versus 270 (235-310) against serotype 4 (GMR 0·88 [0·72-1·09]). Reactogenicity profiles were similar across treatment groups. Most unsolicited adverse events after any injection were non-serious and systemic in nature. During the study, 60 serious adverse events were reported in 58 participants (14 in three-dose group, 26 in two-dose group, 18 in one-dose group), mostly infection and infestations or injury, poisoning, and procedural complications. No serious adverse events of special interest or admissions to hospital for dengue occurred. Two deaths occurred, unrelated to study treatment. INTERPRETATION: A two-dose CYD-TDV regimen might be an alternative to the licensed three-dose regimen in individuals who are dengue seropositive at baseline and aged 9 years and older. Vaccination with a reduced number of doses could lead to improved vaccine compliance and coverage, especially in low-resource settings. FUNDING: Sanofi Pasteur.

Dose-Dependent Behavioral and Antioxidant Effects of Quercetin and Methanolic and Acetonic Extracts from Heterotheca inuloides on Several Rat Tissues following Kainic Acid-Induced Status Epilepticus.

Kainic acid (KA) has been used to study the neurotoxicity induced after status epilepticus (SE) due to activation of excitatory amino acids with neuronal damage. Medicinal plants can protect against damage caused by KA-induced SE; in particular, organic extracts of Heterotheca inuloides and its metabolite quercetin display antioxidant activity and act as hepatoprotective agents. However, it is unknown whether these properties can protect against the hyperexcitability underlying the damage caused by KA-induced SE. Our aim was to study the protective effects (with regard to behavior and antioxidant activity) of administration of natural products methanolic (ME) and acetonic (AE) extracts and quercetin (Q) from H. inuloides at doses of 30 mg/kg (ME30, AE30, and Q30 groups), 100 mg/kg (ME100, AE100, and Q100 groups), and 300 mg/kg (ME300, AE300, and Q300 groups) against damage in brain regions of male Wistar rats treated with KA. We found dose-dependent effects on behavioral and biochemical studies in the all-natural product groups vs. the control group, with decreases in seizure severity (Racine's scale) and increases in seizure latency (p < 0.05 in the ME100, AE100, Q100, and Q300 groups and p < 0.01 in the AE300 and ME300 groups); on lipid peroxidation and carbonylated proteins in all brain tissues (p < 0.0001); and on GPx, GR, CAT, and SOD activities with all the treatments vs. KA (p ≤ 0.001). In addition, there were strong negative correlations between carbonyl levels and latency in the group treated with KA and in the group treated with methanolic extract in the presence of KA (r = -0.9919, p = 0.0084). This evidence suggests that organic extracts and quercetin from H. inuloides exert anticonvulsant effects via direct scavenging of reactive oxygen species (ROS) and modulation of antioxidant enzyme activity.

Association between employee benefits and frailty in community-dwelling older adults.

AIM: The phenotype of frailty has been associated with an increased vulnerability for the development of adverse health-related outcomes. The origin of frailty is multifactorial and financial issues could be implicated, as they have been associated with health status, well-being and mortality. However, the association between economic benefits and frailty has been poorly explored. Therefore, the objective was to determine the association between employee benefits and frailty. METHODS: A cross-sectional study of 927 community-dwelling older adults aged 70 years and older participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty was carried out. Employee benefits were established according to eight characteristics: bonus, profit sharing, pension, health insurance, food stamps, housing credit, life insurance, and Christmas bonus. Frailty was defined according to a slightly modified version of the phenotype proposed by Fried et al. Multinomial logistic regression models were run to determine the association between employee benefits and frailty adjusting by sociodemographic and health covariates. RESULTS: The prevalence of frailty was 14.1%, and 4.4% of participants rated their health status as "poor." Multinomial logistic regression analyses showed that employee benefits were statistically and independently associated with the frail subgroup (OR 0.85; 95% CI 0.74-0.98; P = 0.027) even after adjusting for potential confounders. CONCLUSIONS: Fewer employee benefits are associated with frailty. Supporting spreading employee benefits for older people could have a positive impact on the development of frailty and its consequences. Geriatr Gerontol Int 2016; 16: 606-611.

Draft Genome Sequence of an Extensively Drug-Resistant Acinetobacter baumannii Indigo-Pigmented Strain.

Last year in 2013, we reported an outbreak due to indigo-pigmented Acinetobacter baumannii strains in a hospital from Buenos Aires, Argentina. Here, we present the draft genome sequence of one of the strains (A. baumannii A33405) involved in the outbreak. This isolate was categorized as extensively drug-resistant (XDR) and harbors different genetic elements associated with horizontal genetic transfer and multiple antibiotic resistances.

General trends in selectively driven codon usage biases in the domain archaea.

Since the advent of rapid techniques for sequencing DNA in the mid 70's, it became clear that all codons coding for the same amino acid are not used according to neutral expectations. In the last 30 years, several theories were proposed for explaining this fact. However, the most important concepts were the result of analyses carried out in Bacteria, and unicellular and multicellular eukaryotes like mammals (in other words, in two of the three Domains of life). In this communication, we study the main forces that shape codon usage in Archaeae under an evolutionary perspective. This is important because, as known, the orthologous genes related with the informational system in this Domain (replication, transcription and translation) are more similar to eukaryotes than to Bacteria. Our results show that the effect of selection acting at the level of translation is present in the Domain but mainly restricted to only a phylum (Euryarchaeota) and therefore is not as extended as in Bacteria. Besides, we describe the phylogenetic distribution of translational optimal codons and estimate the effect of selection acting at the level of accuracy. Finally, we discuss these results under some peculiarities that characterize this Domain.

Trends in amino acid usage across the class Mollicutes.

Many studies have explored the mechanisms involved in relative amino acid usage (RAAU) in a variety of prokaryotes and eukaryotes. A strong bias was observed in highly expressed genes (HEGs) of endosymbiotic bacteria. By means of correspondence analysis, we studied the major trends affecting internal variability of RAAU in Mollicutes. The principal trend is related to the usage of smaller, less aromatic, and GC-rich coded amino acids in HEGs. Given the nature of the genetic code, these properties are linked among them. Expectedly, we found a slow evolutionary rate of HEGs, which is likely driven by purifying selection. On the other hand, the rest of the genes accumulate rapid changes as a result of the extreme mutational bias toward A + T of the genomes and genetic drift, increasing internal variability. Amino acid changes across the phylogeny of the group were traced in order to estimate the mean molecular weight and aromaticity trends in each branch. Finally, we compared amino acid usage bias within and between Mollicutes and the free-living Firmicutes.

Discrepancia entre los diagnósticos clínicos y por autopsia en un hospital pediátrico de tercer nivel / Discrepancy between clinical diagnoses versus autopsy findings in a third-level pediatric hospital

Introducción. La utilidad de la autopsia ha sido reconocida ampliamente para fines de educación médica y en la evaluación de la calidad diagnóstica y terapéutica. Desde 1972 hasta 2002, no se ha demostrado un descenso en el número de discrepancias entre los diagnósticos clínicos y de autopsia. El presente estudio permite determinar la concordancia entre los diagnósticos clínicos y de autopsia en una institución pediátrica de tercer nivel, como una herramienta para mejorar la calidad de atención médica. Los objetivos fueron: 1. Obtener el porcentaje de discordancia entre los diagnósticos clínicos y por autopsia en el Hospital Infantil de México Federico Gómez en el período de un año. 2. Determinar, de acuerdo a la clasificación de Goldman modificada por Battle, cuáles son las discrepancias más frecuentes. 3. Calcular la posible asociación entre número de ingresos, tiempo de hospitalización, edad del médico tratante y edad del paciente con el grado de discordancia entre los diagnósticos. Material y métodos. Se efectuó un estudio retrospectivo, observacional, comparativo y transversal. Se analizaron todos los casos de autopsia atendidos entre el 1 de enero y el 31 de diciembre de 2004. Las variables estudiadas fueron: edad, género, número de ingresos y su duración, principal servicio tratante, tipo de autopsia, diagnóstico clínico principal, probable causa de muerte clínica y por autopsia. Resultados. En 2004 se registraron 209 defunciones, con 62 autopsias (29.7%). Hubo discrepancia en 15 casos (24.6%), y de acuerdo a los criterios de Goldman modificados por Battle, se encontró error clase I en 5 casos (8.2%) y clase II en 4 casos (6.6%). No hubo diferencias estadísticamente significativas entre los tipos de error cuando se compararon los pacientes por grupo de edad, duración de la hospitalización, número de ingresos y edad del médico tratante. Conclusión. El mayor número de discrepancias entre diagnósticos clínicos y por autopsia se observó en casos con enfermedades infecciosas. Esta discordancia es similar a la reportada en otros sitios del mundo.

Introduction. The autopsy has been recognized as a useful tool for medical education and for quality improvement, evaluating therapeutic and diagnostic measures. In the last 50 years, the autopsy rates have constantly declined. Interestingly, between 1972 and 2002, the discrepancies between clinical diagnoses and autopsy findings haven't diminished, even with all the technological improvements now available. This research enables us to determine the discrepancy rate between our clinical diagnosis and autopsy results, as well as the main diseases that need diagnostic or therapeutic improvements in our hospital. Our objectives were: 1. To obtain the discrepancy rate between clinical diagnoses and autopsy findings. 2. To determine the most frequent type of discrepancy, according with the Goldman criteria, modified by Battle, and 3. To evaluate the possible association of these discrepancies with the number of admissions, length of stay, patient's age and physician's age. Material and methods. A retrospective, observational, comparative and transversal study. Sample: all cases that had an autopsy between January 1st and December 31th 2004. Cases with an incomplete record were excluded. The main variables analyzed were: age, gender, number of admissions and their length of stay, main clinical service, type of autopsy, main clinical and autopsy diagnoses and probable cause of death. Results. In the year 2004 there were 209 deaths registered with 62 autopsies (29.7% rate). We found a discrepancy in the main clinical diagnosis in 15 cases (24.6%); and, according with the Goldman criteria, modified by Battle, we found a class I discrepancy in 5 cases (8.2%) and a class II discrepancy in 4 cases (6.6%). We didn't find significant statistical differences in patients older than a year compared with patients less than 1 year old. There were no significant differences regarding the number of admissions and their length of stay, or variations the artendiag with the attending physician's age. Conclusions. Our main discrepancies were in infectious diseases, similar to other studies. Our discrepancy numbers are similar to others reported in the world. It is important to analyze these cases with the physicians involved, and together learn from our mistakes, working to improve diagnostic and therapeutic measures, and overall, quality of care.

Miositis osificante progresiva con buena respuesta a tratamiento con esteroide intravenoso / Progressive myositis ossificans with good response to intravenous steroid treatment

Introducción. La miositis osificante progresiva es una causa rara de miositis en la infancia, se trata de una alteración que se hereda de forma autosómica dominante, caracterizada por inflamación muscular seguida de fibrosis y calcificación. Material y métodos. Dos pacientes con diagnóstico de miositis osificante cuyas manifestaciones fueron: acortamiento de pulgares y primeros ortejos, así como endurecimiento de tejidos blandos y calcificaciones en cuello y tórax. Recibieron tratamiento convencional con difosfonatos e isotretinoína, con pobre respuesta. Se decidió el empleo de metilprednisolona, se aplicaron tres dosis iniciales a 30 mg por kg de peso por dosis por vía intravenosa, y posteriormente cada mes. Resultados. Los pacientes presentaron mejoría clínica tanto en la clase funcional como en la sintomatología, la cual se ha mantenido a largo plazo. Conclusión. Se propone como alternativa de tratamiento la utilización de metilprednisolona por sus efectos inmunosupresores y antiinflamatorios, sobre todo en aquellos pacientes que no han tenido respuesta al manejo farmacológico convencional.

Introduction. Progressive myositis ossificans is a rare cause of myositis in childhood, is an autosomal dominant inflammatory disorder that results in swelling of muscle followed by fibrosis and calcification. Material and methods. We present 2 cases in which, the main clinical manifestations were congenitally short great toes and thumbs; and hardening of the soft tissues; in both cases calcifications of the neck and the thorax were demonstrated by roentgenograms. The 2 patients received conventional management with diphosphonates and isotretinoine, with poor response to these therapies; because of this we decided to use 3 initial doses of intravenous methylprednisolone (30 mg/kg/doses), and after that, we continued the treatment with monthly applications of methylprednisolone. Results. With this therapy our patients improved; and this was evidenciated by diminishing of calcifications and by improvement in their functional status. Conclusion. In this paper we propose an alternative pharmacological therapy with intravenous methylprednisolone, looking for its antiinflammatory and immunosuppressive effects of steroids; mainly in patients with poor response to conventional treatments.