Immunoglobulins in systemic sclerosis management. A large multicenter experience.

OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.

Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: a novel heterozygous mutation in SLC12A3 gene.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

An Increase in Tryptase on the First Day of Hymenoptera Venom Immunotherapy Might Be a Predictor of Future Systemic Reactions During Treatment.

BACKGROUND AND OBJECTIVE: Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. METHODS: We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. RESULTS: A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 µg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. CONCLUSIONS: A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety.

An increase in tryptase on the first day of hymenoptera venom immunotherapy might be a predictor of future systemic reactions during treatment

Background: Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. Methods: We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. Results: A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 μg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. Conclusions: A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety

Antecedentes: Se ha observado una disminución progresiva del nivel de triptasa sérica (TS) basal durante la inmunoterapia con veneno de himenópteros (ITVH), así como la conservación de la variación circadiana de triptasa en pacientes que han tolerado una repicadura controlada. Ambos hallazgos se han relacionado con la eficacia del tratamiento. Objetivo: Estudiar si la variación (aumento o disminución) de la TS durante el primer día de ITVH se relaciona con un mayor riesgo de presentar reacciones adversas sistémicas (RAS) con futuras dosis de ITVH. Método: Estudio prospectivo de pacientes sometidos a ITVH en pauta de inicio agrupada y que continuaron con el tratamiento durante al menos 6 meses. Se determinó la TS el primer día de ITVH, antes de la primera dosis (triptasa pre-IT) y tras la última dosis (triptasa post-IT). Se analizaron las diferencias entre los dos grupos de pacientes (con o sin RAS). Resultados: Se administraron 160 ITVH a 150 pacientes. El valor medio de TS basal fue 4,3 μg/L, siendo > 11,4 μg/L en 4 casos. Un total de 25 ITVH (15,6%) presentaron RAS. En 64% de los 25 pacientes con RAS, el valor de triptasa post-IT fue más alto que el valor de triptasa pre-IT; el incremento medio fue del 19% en estos pacientes. Encontramos una relación significativa entre este aumento de triptasa el primer día de ITVH y la aparición de RAS con futuras dosis de ITVH (risk ratio 7,6). Esta elevación fue independiente del día de aparición de la reacción, de la gravedad de la misma, así como del valor basal de triptasa. Conclusiones: Un ligero aumento de triptasa el primer día de ITVH es una variable independiente, fuertemente relacionada con un alto riesgo de presentar una futura RAS. Este sencillo biomarcador podría ser útil para mejorar la seguridad de estos pacientes

La patogénesis de la leucemia. Una revisión / The pathogenesis of leukemia. A review

La leucemia infantil es el cáncer pediátrico principal, a pesar del éxito en el tratamiento, la causa de esta enfermedad aún no tiene un mecanismo molecular completamente conocido. Los mecanismos epigenéticos pueden causar cambios en la función de los genes y participar en el desarrollo del cáncer, por ejemplo la leucemia. Además la hipótesis sobre la infección está ganando más evidencia en el rol de la patogénesis de la leucemia. Asimismo las aberraciones cromosómicas, en particular las translocaciones y sus correspondientes fusiones de genes, juegan un papel importante en las etapas iniciales de la tumorogénesis. Todo este conocimiento aumentará sustancialmente con el advenimiento de nuevas y poderosas herramientas para la investigación que permita detectar reordenamientos citogenéticos.

Consideraciones anestésicas en el síndrome de Miller Fisher / No disponible

No disponible

Analysis of shielding calculation methods for 16- and 64-slice computed tomography facilities.

The new multislice computed tomography (CT) machines require some new methods of shielding calculation, which need to be analysed. NCRP Report No. 147 proposes three shielding calculation methods based on the following dosimetric parameters: weighted CT dose index for the peripheral axis (CTDI(w, per)), dose-length product (DLP) and isodose maps. A survey of these three methods has been carried out. For this analysis, we have used measured values of the dosimetric quantities involved and also those provided by the manufacturer, making a comparison between the results obtained. The barrier thicknesses when setting up two different multislice CT instruments, a Philips Brilliance 16 or a Philips Brilliance 64, in the same room, are also compared. Shielding calculation from isodose maps provides more reliable results than the other two methods, since it is the only method that takes the actual scattered radiation distribution into account. It is concluded therefore that the most suitable method for calculating the barrier thicknesses of the CT facility is the one based on isodose maps. This study also shows that for different multislice CT machines the barrier thicknesses do not necessarily become bigger as the number of slices increases, because of the great dependence on technique used in CT protocols for different anatomical regions.

Experimental procedure for measuring and comparing head-neck-trunk posture and movements caused by different progressive addition lens designs.

This study demonstrates that appropriate measurement procedures can detect differences in head movement in a near reading task when using three different progressive addition lenses (PALs). The movements were measured using an anatomical reference system with a biomechanical rationale. This reference system was capable of representing rotations for comparing head flexion relative to trunk, head flexion relative to neck, head rotation relative to trunk and trunk flexion. The subject sample comprised 31 volunteers and three PAL designs with different viewing zones were selected. Significant differences were found between the lenses for three of the seven movement parameters examined. The differences occurred for both vertical and horizontal head movements and could be attributed to aspects of the PAL design. The measurement of the complete kinematic trunk-neck-head chain improved the number of differences that were found over those in previous studies. STATEMENT OF RELEVANCE: The study proposes a methodology based on a biomechanical rationale able to differentiate head-neck-trunk posture and movements caused by different progressive addition lens designs with minimum invasiveness. This methodology could also be applied to analyse the ergonomics of other devices that restrict the user's field of view, such as helmets, personal protective equipment or helmet-mounted displays for pilots. This analysis will allow designers to optimise designs offering higher comfort and performance.