Metastatic Crohn's disease. Response to adalimumab dose intensification

Inflammatory bowel disease is accompanied by extraintestinal manifestations in a high percentage of patients. Cutaneous lesions are the second most prevalent of these manifestations, and within these, metastatic Crohn's disease is one of the least common, being the least frequent specific cutaneous manifestation of Crohn's disease. This entity includes cutaneous and subcutaneous lesions with a non-caseating granulomatous appearance on histological analysis identical to that of Crohn's disease. These lesions are not found adjacent to the digestive tract. Due to the low prevalence of these manifestations, conclusive trials on the treatment of choice have not been performed and there is no well-defined therapeutic strategy. Distinct therapies with varying results have been reported. We report the case of a female patient with longstanding and complex Crohn's disease who developed metastatic cutaneous manifestations while receiving adalimumab. The cutaneous manifestations responded well to dose intensification of this drug. A review of the literature is provided.     

Rol de los microARN en las enfermedades pulmonares

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression. They actively participate in the modulation of important cell physiological processes and are involved in the pathogenesis of lung diseases such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. A better understanding of the role that miRNAs play in these diseases could lead to the development of new diagnostic and therapeutic tools. In this review, we discuss the role of some miRNAs in different lung diseases as well as the possible future of these discoveries in clinical applications.     

Heat treatment following surface silanization in rebonded tribochemical silica-coated ceramic brackets: shear bond strength analysis

Objective

This study aimed to evaluate the effects of heat treatment on the tribochemical silica coating and silane surface conditioning and the bond strength of rebonded alumina monocrystalline brackets.

Material and Methods

Sixty alumina monocrystalline brackets were randomly divided according to adhesive base surface treatments (n=20): Gc, no treatment (control); Gt, tribochemical silica coating + silane application; Gh, as per Gt + post-heat treatment (air flux at 100ºC for 60 s). Brackets were bonded to the enamel premolars surface with a light-polymerized resin and stored in distilled water at 37ºC for 100 days. Additionally, half the specimens of each group were thermocycled (6,000 cycles between 5-55ºC) (TC). The specimens were submitted to the shear bond strength (SBS) test using a universal testing machine (1 mm/min). Failure mode was assessed using optical and scanning electron microscopy (SEM), together with the surface roughness (Ra) of the resin cement in the bracket using interference microscopy (IM). 2-way ANOVA and the Tukey test were used to compare the data (p>0.05).

Results

The strategies used to treat the bracket surface had an effect on the SBS results (p=0.0), but thermocycling did not (p=0.6974). Considering the SBS results (MPa), Gh-TC and Gc showed the highest values (27.59±6.4 and 27.18±2.9) and Gt-TC showed the lowest (8.45±6.7). For the Ra parameter, ANOVA revealed that the aging method had an effect (p=0.0157) but the surface treatments did not (p=0.458). For the thermocycled and non-thermocycled groups, Ra (µm) was 0.69±0.16 and 1.12±0.52, respectively. The most frequent failure mode exhibited was mixed failure involving the enamel-resin-bracket interfaces.

Conclusion

Regardless of the aging method, Gh promoted similar SBS results to Gc, suggesting that rebonded ceramic brackets are a more effective strategy.     

Low-level laser therapy combined with platelet-rich plasma on the healing calcaneal tendon: a histological study in a rat model

The objective of this study was to investigate the effects of low-level laser therapy (LLLT) treatment alone (λ?=?660 nm and λ?=?830 nm) or associated with platelet-rich plasma (PRP). We used 54 male rats divided into six groups, with nine animals each: group 1, partial tenotomy; group 2 (GII), PRP; group 3 (GIII): λ660?nm; group 4 (GIV), λ830?nm; group 5 (GV), PRP + λ660?nm; and group 6 (GVI), PRP + λ830?nm. The protocol used was power density 0.35 W/cm², energy 0.2 J, energy density 7.0 J/cm², time 20 s per irradiated point, and number of points 3. Animals in groups GII, GV, and GVI received treatment with PRP, consisting of a single dose of 0.2 mL directly into the surgical site, on top of the tenotomy. Animals were killed on the 13th day post-tenotomy and their tendons were surgically removed for a quantitative analysis using polarization microscopy. The percentages of collagen fibers of types I and III were expressed as mean ± SD. Higher values of collagen fibers type I were obtained for groups GV and GVI when compared with all other groups (p?<?0.05), whereas groups GIII and GIV showed no significant difference between them (p?>?0.05). For collagen type III, a significant difference was observed between GII and all other groups (p?<?0.5), but no significant difference was found between GIII and GIV and between GV and GVI. Results showed that the deposition of collagen type I was higher when treatment with PRP and LLLT was combined, suggesting a faster regeneration of the tendon.     

Preliminary prospective explanatory observation on the impact of 3-month steroid therapy on the objective measures of sleep-disordered breathing

Background  

Excess endogenous steroids are a risk factor for obstructive sleep apnea (OSA). The role of exogenous steroids in this setup is not known. In this study, we prospectively looked at the consequences of a 3-month steroid treatment on the objective measures of sleep-disordered breathing.     

Factors predicting the Montreal cognitive assessment (MoCA) applicability and performances in a stroke unit

The evaluation of cognitive status is not routine in the acute stroke setting. We aimed to investigate feasibility, applicability, and performances of the Montreal cognitive assessment (MoCA) in acute stroke patients. Consecutive stroke patients (ischemic or hemorrhagic) admitted to one stroke unit were evaluated 5–9 days after stroke with MoCA (score range: 0–30; higher scores indicate better cognitive performance). Pre-morbid functional and cognitive status was assessed by a structured interview to caregivers. Neuroimaging data regarding index stroke and pre-existing lesions were collected. From December 2009 to December 2010, out of 207 patients with stroke, 137 (66 %) were enrolled [mean age 69.2 ± 14.8 years; males 62 %; mean National Institute of Health and Stroke Scale (NIHSS) score 5.9 ± 7.9]. The most common reason for non-enrolment was unfitting the time window inclusion criteria. MoCA was entirely applicable to 113/137 (82.5 %) patients and the mean score was 17.8 ± 7.1. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR (95 % CI) = 1.4 (1.2–1.7) for each point], left sided lesions [OR (95 % CI) = 18.8 (2.3–155.2)], and worse pre-morbid functional status [OR (95 % CI) = 0.7 (0.6–0.9) for each point of the instrumental activity of daily living scale]. Factors influencing MoCA performance were low education (β = 0.264, p < 0.01), higher NIHSS scores (β = ?0.277, p < 0.01) and worse pre-morbid functional status (β = 0.504, p < 0.001). MoCA administration is feasible in acute patients with mild-to-moderate stroke, with lesion location, stroke severity, and pre-morbid functional status as major determinants of its applicability and performance. MoCA seems to reveal some degree of cognitive deficit even in patients with mild stroke.     

Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis

Journal of Neurology - TK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of...     

Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity

Endogenous levels of glucocorticoids rise during pregnancy to warrant development and maturation of the fetal organs close to birth. However, during most of the gestation, the fetus is protected from excessive biologically active endogenous glucocorticoids by placental and fetal expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Maternal stress, which may overwhelm placental 11β-HSD2 activity with high glucocorticoid levels, or administration of synthetic glucocorticoids to improve the survival chances of the premature newborn, are associated to postnatal increased risk for immune diseases. Fetal exposure to excessive glucocorticoids may underlie this altered postnatal immunity. Here, we revise the role that placental and fetal 11β-HSD2, fetal glucocorticoid exposure, and programming of the offspring’s the hypothalamic-pituitary-adrenal (HPA) axis play on concerted steps in immune fetal development. We could identify gaps in knowledge about glucocorticoid-induced programming of immune diseases. Finally, based on current evidence about glucocorticoid and HPA axis-mediated immune regulation, we hypothesize on mechanisms that could drive the enhanced risk for atopies, infections, and type I diabetes in offspring that were prenatally exposed to glucocorticoids.     

Expression of nuclear insulin receptor substrate 1 in breast cancer

BACKGROUND: Insulin receptor substrate 1 (IRS-1), a cytoplasmic protein transmitting signals from the insulin and insulin-like growth factor 1 receptors, has been implicated in breast cancer. Previously, it was reported that IRS-1 can be translocated to the nucleus and modulate oestrogen receptor alpha (ERalpha) activity in vitro. However, the expression of nuclear IRS-1 in breast cancer biopsy specimens has never been examined. AIMS: To assess whether nuclear IRS-1 is present in breast cancer and non-cancer mammary epithelium, and whether it correlates with other markers, especially ERalpha. Parallel studies were carried out for the expression of cytoplasmatic IRS-1. METHODS: IRS-1 and ERalpha expression was assessed by immunohistochemical analysis. Data were evaluated using Pearson's correlation, linear regression and receiver operating characteristic analysis. RESULTS: Median nuclear IRS-1 expression was found to be low in normal mammary epithelial cells (1.6%) and high in benign tumours (20.5%), ductal grade 2 carcinoma (11.0%) and lobular carcinoma (approximately 30%). Median ERalpha expression in normal epithelium, benign tumours, ductal cancer grade 2 and 3, and lobular cancer grade 2 and 3 were 10.5, 20.5, 65.0, 0.0, 80 and 15%, respectively. Nuclear IRS-1 and ERalpha positively correlated in ductal cancer (p<0.001) and benign tumours (p<0.01), but were not associated in lobular cancer and normal mammary epithelium. In ductal carcinoma, both nuclear IRS-1 and ERalpha negatively correlated with tumour grade, size, mitotic index and lymph node involvement. Cytoplasmic IRS-1 was expressed in all specimens and positively correlated with ERalpha in ductal cancer. CONCLUSIONS: A positive association between nuclear IRS-1 and ERalpha is a characteristic for ductal breast cancer and marks a more differentiated, non-metastatic phenotype.