Abstract
Background
Perianal Crohn's disease(PCD) significantly impacts quality of life with poor long-term prognosis. Anti-tumor necrosis factor(anti-TNF) therapy improves fistula closure rates. ...However, achieving permanent closure remains challenging. Our aim is to evaluate the relation between antiTNF(infliximab (IFX) and adalimumab(ADA) serum concentrations at induction(w2 and 6), and clinical and radiological outcomes at w24 and w52
Methods
We conducted a single tertiary center, retrospective, cohort study including patients with an established diagnosis of PCD treated with antiTNF because of perianal activity. Variables related to their PCD(phenotype, location, fistulas type) were collected. Regarding treatment, we collected serum levels at week 2,6,24 and 52, concomitant treatment and setons presence. We defined clinical response as the absence of drainage on physical examination and clinical remission as the absence of external fistula openings. Radiological response was defined as the absence of T2 hypersignal, gadolinium enhancement, abscess and proctitis in pelvic MRI
Results
65 patients were included, baseline characteristics are in Table1. None of the demographic characteristics collected were statistically significant related to clinical or radiological response although non smokers(p=0.01), ileal(p=0.02) and non-stricturing disease(p=0.01) had statistically significant higher drug levels. Taking into account the clinical response at w52, IFX mean levels at w2 were 25.8µg/mL(SD 4.1) in non responders and 30.9µg/mL(SD 14) in responders(p=0.39). At w6 they were 17.2µg/mL(SD 12.2) and 19.4µg/mL(SD 13.8) respectively(p=0.7). ADA mean levels at w2 were 13.3µg/mL(SD 7.7) in non responders and 14µg/mL(SD 6.3) in responders(p=0.87). At w6 they were 10.1µg/mL(SD 3.3) and 12µg/mL(SD 6.1) respectively(p= 0.59). For radiological response at w52 IFX mean levels at w2 were 27µg/mL(SD 15.3) in non responders and 32.7µg/mL(SD 14.5) in responders(p=0.45). At w6 the mean levels were 15.9µg/mL(SD 6.7) and 23.7µg/mL(SD 14.8) respectively(p=0.27). In ADA group the mean levels at w2 were 14.8µg/mL(SD 7.6) in responders and only one patient did not respond. At w6 ADA mean levels were 12.3µg/mL(SD 5.9) in non responders and 12.7µg/mL(SD 6.2) in responders(p=0.94). Early response at w24 was related with a long-term response at w52, 89.9% of the patients who responded at w52, had already responded at w24.
Conclusion
In our study we observed that almost 90% of the patients who had an early response also responded at w52, so trying to achieve an early response should be an aim in clinical practice. Despite the limited number of patients, our study shows a trend in the relationship between higher antiTNF levels and clinical and radiological response rates
Abstract
Background
There is little scientific evidence available about the results in terms of clinical and biochemical response after intensification with intravenous (IV) ustekinumab (UST) as a ...therapeutic strategy to be used in patients with refractory Crohn’s disease (CD) who are receiving subcutaneous (SC) treatment with said drug.
Methods
Patients with CD in stable follow-up at Hospital Universitario La Paz (Madrid), who were undergoing intensified treatment with IV UST, were recruited. The objective of the study was to assess the clinical and analytical response and drug levels 12 weeks after the change from subcutaneous to intravenous UST.
Results
27 patients were retrospectively included, all of them with previous treatment with UST SC. In Table 1 baseline characteristics are collected.
Out of the 27 patients included, 4/27 were under treatment with UST in first line, 10/27 in second line, 9/27 in third line and 4/27 had failed to three biologics.
The reason for intensification with IV UST was the lack of response to treatment in the 27 patients, 7 of them (25.93%) being found in the context of post-surgical recurrence. On the other hand, 10 patients (37.03%) were already under treatment with intensified SC UST, while the remaining 17 patients (62.96%) were under treatment with a standard schedule of SC UST every 8 weeks.
At the baseline visit, prior to the change to IV UST, differences in levels were observed between intensified and non-intensified patients (7216 vs 2842, p=0,00005). However, no significant differences were appreciated between these two groups 12 weeks after IV intensification (7949 vs 7937; p=0,99).
In patients with intensified UST SC was observed a decrease in fecal calprotectin 12 weeks after starting IV intensification, going from a mean of 1463 to 751, although the differences were not significant (p=0,14).
In Figure 1 is shown improvement in fecal calprotectin levels and in Figure 2 improvement in UST levels in blood is reflected, both parameters quantified 12 weeks after intravenous intensification of the drug.
In Table 2 data derived from the analysis of the clinical activity and determinations of CRP and calprotectin are collected, before performing the intensification with UST IV and 12 weeks after it.
Conclusion
In our experience, change to intravenous ustekinumab in maintenance led to an improvement in the clinical and biochemical response in patients with Crohn’s disease (even in patients already intensified). Likewise, an increase in drug levels was observed 12 weeks after the change from subcutaneous to intravenous treatment.
Abstract Objectives The main challenge in treating bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the absence of an effective established treatment. We aimed to compare different ...potentially preventive treatments for BRONJ after dental extractions in zoledronic acid (ZA)-treated animals. We studied the local application of different combinations of adipose-derived stem cells (ASCs) with or without previous stimulation with bone morphogenetic protein 2 (BMP-2) and platelet-rich plasma (PRP) in rats. Material and methods Fifty-six male Wistar rats were treated with ZA for 9 weeks. Dental extractions were performed in the eighth week, and the animals were divided into 4 groups. In group 1 (n = 14), alveolar coverage with mucoperiosteal flap was performed. In group 2 (n = 14), PRP was applied over the sockets and covered with the flap. In group 3 (n = 15), allogeneic ASCs with PRP were applied and covered with the flap. In group 4 (n = 13), animals were treated with ASCs cultured with BMP-2, PRP, and flap coverage. Histologic, fluorescence, and radiologic studies of the maxillae were performed. Results ASC-treated animals showed lower frequency of osteonecrosis (14% vs 50%, p = 0.007) and greater bone turnover ( p = 0.024) and osteoclast count ( p = 0.045) than those not receiving the ASC treatment. Conclusions In this high-risk model, ASC-based treatments seem to prevent BRONJ more effectively than mucosal flap with or without PRP. The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results.
Rotator cuff repairs have shown a high level of re-ruptures. We hypothesized that the use of adipose-derived stem cells (ASC) could improve the biomechanical and histological properties of the ...repair.
Controlled experimental study conducted on 44 BDIX rats with section and repair of the supraspinatus tendon and randomization to one of three groups: group A, no intervention (control); group B, local applications of a fibrin sealant; and group C, application of the fibrin sealant with 2 x 10(6) ASC. At 4 and 8 weeks a biomechanical and histological analysis was performed.
There were no differences in load-to-failure at 4 and 8 weeks between groups. The load-to-failure did increase between week 4 and week 8. Histologically the tendon-to bone union showed a disorganized fibrovascular tissue. Group C showed a different inflammatory pattern, with less presence of neutrophils and more presence of plasma cells.
The use of ASC does not improve the biomechanical or histological properties of the repair site. More studies are needed to improve techniques that enhance the healing site of the repair.
Resumen Introducción y objetivos El plasma rico en factores plaquetarios (PRP) ha sido utilizado como terapia adyuvante en el tratamiento de úlceras crónicas de miembros inferiores (UCMI), con ...resultados particularmente esperanzadores en las úlceras neuropáticas. Sin embargo, su uso en úlceras venosas e hipertensivas ha sido menos estudiado. Nuestro objetivo es valorar la seguridad y factibilidad del uso del PRP en UCMI y estimar sus beneficios en la cicatrización dirigida. Material y métodos Se trata de un estudio prospectivo. Fueron seleccionados 11 pacientes con úlceras en miembros inferiores de más de 6 semanas de evolución, de etiología no isquémica. Se administró PRP en inyección subcutánea perilesional y aplicación tópica, en 4 sesiones separadas por una semana. Se suministraron cuestionarios de calidad de vida (SF-12), se registró el dolor (escala visual analógica) y el perímetro de la úlcera antes y después de su aplicación. Resultados Hubo predominancia de mujeres (8/11 = 73%) y de úlceras venosas (7/11 = 64%) sobre las hipertensivas (4/11 = 36%). La mediana de edad fue de 79 años y el tiempo medio de evolución de la úlcera de 17 meses (6-108 meses). Se evidenció una disminución estadísticamente significativa del dolor (p < 0,05) y mejoría mental y física de la calidad de vida (p < 0,05). Se evidenció una reducción media en el área de las úlceras del 60%, con 5 cicatrizaciones completas. No se registraron eventos adversos. Conclusión La aplicación local de PRP en úlceras crónicas de miembros inferiores representa una herramienta válida, de uso práctico en la cicatrización dirigida, que puede mejorar la calidad de vida de estos pacientes, siendo particularmente útil en el control del dolor local.
Abstract
Background
Platelet-related markers associated with a procoagulant state have been described for Immune-mediated Inflammatory Diseases (IMIDs), but a broader profiling of these abnormalities ...in Inflammatory Bowel Disease (IBD) is lacking.
Methods
Cross-sectional study to describe and compare platelet biomarkers of IBD outpatients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC), vs healthy controls (HC).
Patients over 18 years old with a diagnosis of CD or UC according to the European Crohn’s and Colitis Organization (ECCO) criteria were included. Fecal calproctectin (Fcal) >=150ug/g was used as a cutoff level for active disease. Exclusion criteria for IBD patients are listed under Table 1.
Fibrinogen (FBG) receptor on platelet’s surface was determined with anti-CD41 and anti-CD61 monoclonal antibodies (mAbs); and von Willebrand factor receptor with anti-CD42a and anti-CD42b mAbs.
Platelet activation markers TRAP and ADP-induced activation of fibrinogen (FBG) receptor, and P-selectin (Psel) and CD63 exposure were determined, respectively, through binding of PAC1, anti-P-selectin and anti-CD63 (mAbs).
All variables were determined by flow cytometry.
Results
55 patients (27 CD, 28 UC) and 75 HC have been included. 43 IBD patients had active disease (21 CD, 22 UC). Complete baseline characteristics of the IBD population are described in Table 1.
Basal Psel (% of positive cells) was increased in CD vs UC (median IQR: 5.64 4,4-10,4 vs 2,9 1,8-6,8, p=0,02) and vs HC (3,5 1,4-6,8, p=0,008). ADP-induced Psel was increased in CD vs HC (mean, SD: 49.92, SD 12.75 vs 41.943, SD13.15, p=0,007). Basal CD63 (% of positive cells) was significantly higher in active IBD vs HC (W = 1143, p = 0.02) and inactive IBD vs HC (W = 528, p= 0.006). CD42a (% of positive cells) was decreased in IBD vs HC (W = 1128.00, p=0.007) and CD vs HC (W = 777.00, p =0.04). CD42b (% of positive cells) was also decreased in IBD vs HC (mean, SD: 106.9 SD, 17.32 vs 115.7, SD 28.42, p=0,01) and CD vs HC (104.06 SD 14.49, p=0,03). No differences in basal or TRAP/ADP induced PAC binding, and in CD41 or CD61 expression were observed among groups. Multiple linear regression showed association of Fcal with basal Psel in IBD patients (p=0,02); and Spearman’s correlation showed negative moderate correlation between Fcal and basal Psel (r=0,3; p=0,003)
Conclusion
Features of platelets in IBD suggest increased platelet degranulation and reduced vWF receptor with regards to healthy controls, specially in CD, but no differences in FBG-related receptors. Inverse moderate correlation between Fcal and Psel in IBD patients suggests depletion of intra-platelet granules at higher levels of gut inflammation.
This paper aims to estimate the impact of different labour market transitions on wages by applying recent panel data methods designed to address problems of sample selectivity, unobserved ...heterogeneity and endogeneity to longitudinal data on individual workers from six European countries for the period 1995–2001. In particular, we examine whether job interruptions due to unemployment or inactivity have any significant influence on subsequent wages, the magnitude of this influence and whether differences in relative wage gains/losses exist across countries. The main findings are explained in terms of differences in institutions.
Células para curar. Del corazón al todo García-Olmo, D.; García-Arranz, M.
Anales de pediatría (Barcelona, Spain : 2003),
April 2011, Letnik:
74, Številka:
4
Journal Article
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