Survival, Causes of Death, and Prognostic Factors in Systemic Sclerosis: Analysis of 947 Brazilian Patients

Objective. To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). Methods. From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. Results. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS <20). Conclusion. Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc. (First Release Aug 15 2012; J Rheumatol 2012;39:1971-8; doi:10.3899/jrheum.111582)

Mechanical thrombectomy with solitaire stent retrieval for acute ischemic stroke in a Brazilian population

OBJECTIVE: Large vessel occlusion in acute ischemic stroke is associated with low recanalization rates under intravenous thrombolysis. We evaluated the safety and efficacy of the Solitaire AB stent in treating acute ischemic stroke. METHODS: Patients presenting with acute ischemic stroke were prospectively evaluated. The neurological outcomes were assessed using the National Institutes of Health Stroke Scale and the modified Rankin Scale. Time was recorded from the symptom onset to the recanalization and procedure time. Recanalization was assessed using the thrombolysis in cerebral infarction score. RESULTS: Twenty-one patients were evaluated. The mean patient age was 65, and the National Institutes of Health Stroke Scale scores ranged from 7 to 28 (average 17+/-6.36) at presentation. The vessel occlusions occurred in the middle cerebral artery (61.9%), distal internal carotid artery (14.3%), tandem carotid occlusion (14.3%), and basilar artery (9.5%). Primary thrombectomy, rescue treatment and a bridging approach represented 66.6%, 28.6%, and 4.8% of the performed procedures, respectively. The mean time from symptom onset to recanalization was 356.5+/-107.8 minutes (range, 80-586 minutes). The mean procedure time was 60.4+/-58.8 minutes (range, 14-240 minutes). The overall recanalization rate (thrombolysis in cerebral infarction scores of 3 or 2b) was 90.4%, and the symptomatic intracranial hemorrhage rate was 14.2%. The National Institutes of Health Stroke Scale scores at discharge ranged from 0 to 25 (average 6.9+/-7). At three months, 61.9% of the patients had a modified Rankin Scale score of 0 to 2, with an overall mortality rate of 9.5%. CONCLUSIONS: Intra-arterial thrombectomy with the Solitaire AB device appears to be safe and effective. Large randomized trials are necessary to confirm the benefits of this approach in acute ischemic stroke.

A Modified Technique of Rat Tail Suspension for Longer Periods of Observation

FALCAI MJ, LOUZADA MJQ, DE PAULA FJA, OKUBO R, VOLPON JB. A modified technique of rat tail suspension for longer periods of observation. Aviat Space Environ Med 2012; 83:1176-80. Background: Rat tail suspension is an accepted method to create experimental osteopenia. However, suspension periods longer than 3 wk may cause tail skin sloughing or rat slippage. The hypothesis was that a traction system with skeletal anchorage through one tail vertebra would prolong the suspension time without significant complications. Methods: There were 80 young adult female Wistar rats that were submitted to one of the following interventions: skeletal tail suspension (N = 20), skin tail suspension (N = 20), no intervention (N = 20), and a baseline control (N = 20). All animals were followed up either for 3 (N = 10) or 6 (N = 10) wk. Animals were assessed for clinical signs of stress and tolerance to suspension. The femur evaluation was in terms of mineral density content, mechanical resistance, and histomorphometry. Results/Discussion: All animals reached the 3-wk end point. However, for the 6-wk period, seven animals suspended by the skin traction method were discarded (70%) because of signs of stress and skin sloughing. In contrast, there was one loss in the skeletal suspension group (10%). All suspended animals developed similar osteopenia at 3 wk characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass. At 6 wk, all suspended animals had similar osteopenic parameters, but they were not statistically different from those of the rats in the 3-wk groups. Therefore, suspension longer than 3 wk did not increase the bone deterioration in the femur.

Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy

Background The field cancerization concept in photodamaged patients suggests that the entire sun-exposed surface of the skin has an increased risk for the development of (pre)-malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome. Objectives To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methyl-aminolaevulinate (MAL). Methods Twenty-six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL-PDT with red light (37 J cm(-2)), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal-appearing skin on the field-cancerized area. Immunohistochemical stainings were performed for TP-53, procollagen-I, metalloproteinase-1 (MMP-1) and tenascin-C (Tn-C). Results All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0.001). The AK clearance rate was 89.5% at the end of the study. Two treatment sessions were as effective as three MAL-PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0.001). Also, a significant increase in collagen deposition (P = 0.001) and improvement of solar elastosis (P = 0.002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP-53 expression (not significant), increased procollagen-I and MMP-1 expressions (not significant) and an increased expression of Tn-C (P = 0.024). Conclusions Clinical and histological improvement in field cancerization after multiple sessions of MAL-PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the sun-damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.

Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

Abstract Background Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers. Methods SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. Results Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution. Conclusions The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.

Design methodology of piezoelectric energy-harvesting skin using topology optimization

Abstract This paper describes a design methodology for piezoelectric energy harvester s that thinly encapsulate the mechanical devices and expl oit resonances from higher- order vibrational modes. The direction of polarization determines the sign of the pi ezoelectric tensor to avoid cancellations of electric fields from opposite polarizations in the same circuit. The resultant modified equations of state are solved by finite element method (FEM). Com- bining this method with the solid isotropic material with penalization (SIMP) method for piezoelectric material, we have developed an optimization methodology that optimizes the piezoelectric material layout and polarization direc- tion. Updating the density function of the SIMP method is performed based on sensitivity analysis, the sequen- tial linear programming on the early stage of the opti- mization, and the phase field method on the latter stage

CHO cell adhesion on modified surfaces of different materials.

Epithelial cells are mainly responsible for the formation of tissues that cover the external and internal surfaces of organs like skin, lining of the lungs and intestines. The cells must adhere to substrates and to each other in compliance with certain stimulus. In this way, adhesion properties can be regulated by the cell which simultaneously senses the chemical and mechanical properties of its environment. Their adhesion and growth on biomaterials depends on substrate properties such as surface wettability, topography and chemistry. The aim of this study is to investigate cell-surface interactions using several materials and different surfaces.