Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial

Background Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. Methods We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of >= 0.65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0.965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. Findings All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0.749, below the Bayesian success threshold of 0.965). The 6-month composite primary safety endpoint was 14.4% (30 of 208) for airway bypass versus 11.2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1.00 [Bayesian success threshold >0.95]). Interpretation Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema.

Biological markers and prognosis in recurrent oral cancer after salvage surgery

Objective: To analyze the prognostic effect of epidermal growth factor receptor (EGFR), matrix metalloproteinases 2 and 9, and vascular endothelial growth factor expression in patients with locally recurrent oral carcinoma after salvage surgery. Design: Retrospective cohort study. Settings: Tertiary center cancer hospital. Patients: The charts of 111 patients with local recurrence of oral carcinomas were retrospectively analyzed. The previous treatment consisted of surgery in 33 patients (30.0%), radiotherapy with or without chemotherapy in 46 patients (41.0%), and surgery with adjuvant radiotherapy in 32 patients (29.0%). The expression of EGFR, matrix metalloproteinases 2 and 9, and vascular endothelial growth factor was analyzed with a tissue microarray immunohistochemical technique. Main Outcome Measures: Overall survival and cancer-specific survival (CSS). Results: The recurrences were diagnosed in less than 1 year in 69 patients (62.2%) and in more than 1 year in 42 patients (37.8%). The prognosis was worse in the group with the disease-free interval of less than 1 year (P=.01). Patients with more advanced disease (clinical stage of recurrence, III/IV) had worse rates of CSS (P=.04). Cases that were positive for EGFR had a 3-year CSS of 27.2%, while EGFR-negative cases had a 3-year CSS of 64.3% (P=.001). The expression of matrix metalloproteinases 2 (P=.83) and 9 (P=.15) and vascular endothelial growth factor (P=.86) was not significant in this group. In multivariate analysis, only the disease-free interval and the overexpression of EGFR were associated with a higher risk of cancer death. Conclusions: Local recurrence in oral carcinomas carries a poor prognosis. A disease-free interval of more than 1 year and a EGFR-negative expression are the main prognostic factors related to better CSS in patients treated with salvage surgery.

Prognostic Impact of MYCN, DDX1, TrkA, and TrkC Gene Transcripts Expression in Neuroblastoma

Background. The aims of this study were to define the mRNA expression profiles of MYCN, DDX1, TrkA, and TrkC in biopsy tumor samples from 64 Brazilian patients with neuroblastomas of different risk stages and to correlate altered expression with prognostic values. Procedure. Patients were retrospectively classified into low- (n = 11), intermediate- (n = 18), and high-risk (n = 35) groups using standard criteria. The mRNA levels of the above genes were measured by quantitative real-time polymerase chain reaction. Univariate analyses were performed and survival curves were plotted by the Kaplan-Meier method. Results. Of the 64 patients, 53% were female and 62.5% were older than 18 months. The 5-year overall survival (OS) for the entire cohort was 40.3%, with inferior median OS in patients identified in the intermediate- and high-risk groups. A significant difference in OS with respect to TrkA mRNA expression was found for the high-risk group vs. either the low- or intermediate-risk groups (P < 0.01, log rank test). Within the intermediate-risk group, neuroblastoma patients with positive TrkA mRNA expression had better clinical outcomes than patients with no TrkA transcript expression (P = 0.004). Another difference in OS was only found between the intermediate- and high-risk groups (P < 0.027, log rank test). No significant correlation of mRNA expression and survival outcome could be detected for the MYCN, DDX1. Conclusions. Positive expression of TrkA mRNA may be a clinically useful addition to the current risk classification system, allowing the identification of NB tumors with favorable prognosis. Pediatr Blood Cancer 2011; 56: 749-756. (c) 2010 Wiley-Liss, Inc.

Multiple cranial burr holes as an alternative treatment for total scalp avulsion

Total scalp avulsion is a devastating injury in clinical practice. It often occurs in female adults, being rare in children. The standard treatment for scalp avulsion is microsurgical replantation, when feasible. Coverage becomes a major problem when replantation fails or is contraindicated, resulting in significant morbidity and requiring multiple procedures. In this article, in addition to reviewing the literature, we report a historical method for obtaining skin coverage after failure of replantation. The authors report a case of a 10-year-old girl who had her scalp totally avulsed by an agricultural machine, including her right auricle. Microsurgery scalp replantation was attempted immediately after fluid resuscitation. The surgery failed probably due to the long time interval between trauma and surgery, which resulted in total ischemic time of 11 h and consequently made vascular microanastomosis impracticable. Multiple trephination of the calvarium was performed in order to expose the diploe. After 4 weeks, granulation tissue from the holes began to cover the defect, allowing the formation of a vascular bed suitable for skin grafting. Total scalp avulsion in children is seldom reported in the literature. Therefore, its management is both difficult and challenging. The exposure of the diploe with multiple burr holes is a safe and effective method for treating this injury. It may be considered, along with skin grafting, a good therapeutic alternative to be used when microsurgical replantation fails or is not feasible.

Acute alterations in anorectal manometry induced by proximal and distal sphincterotomy. Experimental studies on piglets

Anal incontinence causes psychological, social and adaptive troubles prejudicial to the quality of life both in children and adults. Therefore, the detailed knowledge of its causes and the improvement of diagnostic and therapeutic methods increase the possibilities of a more adequate social life to patients with congenital anomalies or sphincteric lesions or degenerations. In this work, a manometric study was developed through an experimental model so as to analyze alterations in behavior of muscle groups responsible for the anorectal sphincteric mechanism, previous to and after proximal and distal lesions. Twenty-two pigs aged between 25 and 30 days, weighing 5-7 kg, were randomly divided into two groups. They were submitted to lesions of different levels in the anorectal muscle. The animals were studied by anorectal manometry (rectoanal inhibitory reflex and vector volume) before and after the lesions. The Student t test and the Wilcoxon test were applied for the statistical analyses, considered p <= 0.05. The proximal lesion preserved sphincter relaxation, retarding its closure [speed of relaxation recovery 4.35 +/- 2.10 vs. 2.70 +/- 1.32 mm/s (p = 0.001)], but it reduced the maximum pressure [62.45 +/- 20.02 vs. 40.36 +/- 12.59 mmHg (p = 0.004)] and vector volume [2,749 +/- 921 vs. 1,591 +/- 1,379 mmHg(2)cm (p = 0.005)]. There was an increment in the high-pressure zone [5.09 +/- 1.04 vs. 6.36 +/- 1.50 mm (p = 0.005)], but the asymmetry percentage and the sphincter length were maintained. The distal lesion did not alter the rectoanal inhibitory reflex, the high-pressure zone length, the asymmetry percentage, or the vector volume. Nevertheless, the sphincter length increased [11.82 +/- 2.82 vs. 14.09 +/- 2.39 mm (p = 0.022)] and the maximum pressure decreased [60.55 +/- 22.05 vs. 40.91 +/- 13.41 mmHg (p = 0.004)]. The alterations observed due to proximal lesion of the anorectal sphincter suggest a direct and more important interference of the levator ani muscle in the function of the sphincteric musculature than that caused by the distal lesion.

Bursts of transposition from non-long terminal repeat retrotransposon families of the RTE clade in Schistosoma mansoni

The genus Schistosoma is composed of blood flukes that infect vertebrates, from which three species are major causative agents of human schistosomiasis, a tropical disease that affects more than 200 million people. Current models of the recent evolution of Schistosoma indicate multiple events of migration and speciation from an Asian ancestral species. Transposable elements are important drivers of genome evolution and have been hypothesised to have an important role in speciation. In this work, we describe a comprehensive inventory of Schistosoma mansoni and Schistosoma japonicum retrotransposons, based on their recently published genomic data. We find a considerable difference in retrotransposon representation between the two species (22% and 13%, respectively). A large part of this difference can be attributed to higher representation of two previously described families of S. mansoni retrotransposons (SR2 and Perere-3/SR3), compared with the representation of their closest relative families in S. japonicum. A more detailed analysis suggests that these two S. mansoni families were the subject of recent bursts of transposition that were not paralleled by their S. japonicum counterparts. We hypothesise that these bursts could be a consequence of the evolutionary pressure resulting from migration of Schistosoma from Asia to Africa and their establishment in this new environment, helping both speciation and adaptation. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness analysis of universal childhood vaccination against varicella in Brazil

This study conducts a cost-effectiveness analysis of a childhood universal varicella vaccination program in Brazil. An age and time-dependent dynamic model was developed to estimate the incidence of varicella for 30 years. Assuming a single-dose schedule; vaccine efficacy of 85% and coverage of 80%, the program could prevent 74,422,058 cases and 2905 deaths. It would cost R$ 3,178,396,110 and save R$ 660,076,410 to the society and R$ 365,602,305 to the healthcare system. The program is cost-effective (R$ 14,749 and R$ 16,582 per life-year saved under the societal and the healthcare system`s perspective, respectively). The program`s cost-effectiveness is highly sensitive to the vaccine price and number of doses. (C) 2008 Elsevier Ltd. All rights reserved.

The immunohistochemical profile of oral inflammatory myofibroblastic tumors

Objective. The aim of this study was to demonstrate the immunohistochemical profile of oral inflammatory myofibroblastic tumors (IMTs) along with morphologic analysis. Study design. Three cases diagnosed as oral IMTs were selected to compile an immunohistochemical panel constituted by calponin, caldesmon, Bcl-2, desmin, fibronectin, CD68, Ki-67, S100, anaplastic lymphoma kinase (ALK), alpha-smooth muscle actin, cytokeratins AE1/AE3, muscle-specific actin, CD34, and vimentin. An oral squamous cell carcinoma with a focal area of desmoplastic stroma was used as control for the stained myofibroblastic cells. Results. All oral IMTs were positive for calponin, revealing a strong and diffuse expression in the spindle-shaped cells. The lesions were also positive for vimentin (3/3), fibronectin (3/3), alpha-smooth muscle actin (3/3), and muscle-specific actin (1/3) and negative for h-caldesmon, Bcl-2, desmin, CD68, Ki-67, S100, ALK, cytokeratins AE1/AE3, and CD34. Conclusions. Within the results encountered, the present panel should be of great assistance in the diagnosis of oral IMTs. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 111: 749-756)

Mechanical stability of adhesives under water storage

Objectives. To evaluate the effects of storage condition (wet or dry) and storage time (24 h and 3 months) on the ultimate tensile strength (UTS) of Single Bond (SB), 3M-ESPE; Opti Bond Solo Plus (OB), Kerr; One Step (OS), Bisco, and Prime & Bond NT (PB), Dentsply adhesive resins. Methods. Hourglass-shaped specimens were obtained from a metallic matrix. Each adhesive was dispensed to fill the molds completely and left undisturbed in a dark chamber for 4 min at 37 degrees C for solvent evaporation. They were individually light-cured for 80 s at 500 mW/cm(2) and randomly divided into three groups: 24 h of water storage; 3 months of water storage; 3 months of dry storage. The specimens were tested in tension at 0.5 mm/min using the microtensile method and data were analyzed by two-way ANOVA and SNK tests for each material. Results. Water storage for 3 months did not cause significant changes in the UTS of any of the adhesives (p-value). Values for water storage ranged from 25.9 MPa for Single Bond at 24 h to 32.7 MPa for Prime & Bond NT after 3 months. Dry storage for 3 months yielded significantly higher UTS for most adhesives, which ranged from approximately 20% for Opti Bond to 160% higher values for Single Bond compared to their 3 months wet storage values. Conclusion. The effects of storage condition and time on the UTS of adhesives were material-dependent. (C) 2009 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Morphometric evaluation of the repair of critical-size defects using demineralized bovine bone and autogenous bone grafts in rat calvaria

Objective: To evaluate the repair of critical-size bone defects in rats treated with demineralized bovine bone (DBB) compared with autogenous bone (AB). Material and method: A bone defect of 8 mm in diameter was created in the calvaria of 50 Rattus norvegicus, treated either with DBB or AB. Sub-groups of five rats of each group were killed at 7, 14, 21, 30 and 90 days post-operatively, and the skulls were removed and processed histologically. Histological sections were stained with hematoxylin and eosin. Result: Histological analysis showed complete closure of the defects with new bone at 90 days in group AB, and substitution of the biomaterial by fibrotic connective tissue in the DBB group at 21 days. Morphometric analysis showed that DBB was rapidly absorbed at 14 days, with its volume density decreasing from 47%+/- 0.8% at 7 days to 1.2%+/- 0.41% at 14 days. Subsequently, volume densities of the connective tissue and neoformed bone increased from 51.1%+/- 11.17% to 86.8%+/- 7.92% and from 1.9%+/- 1.13% to 12%+/- 8.02%, respectively, for the same time interval. The volume density of AB particles did not change throughout the experimental periods, but the amount of new bone increased markedly between 7 and 90 days, from 4.5%+/- 1.57% to 53.5%+/- 6.42% (P < 0.05). Conclusion: DBB did not provide complete repair of the defects, with significantly less new bone formation than in the AB group.

Simplified quartessence cosmology

We propose a new class of accelerating world models unifying the cosmological dark sector (dark matter and dark energy). All the models are described by a simplified version of the Chaplygin gas quartessence cosmology. It is found that even for Omega(k) not equal 0, this quartessence scenario depends only on a pair of parameters which can severely be constrained by the cosmological tests. As an example we perform a joint analysis involving the latest SNe type la data and the recent Sloan Digital Sky Survey measurement of baryon acoustic oscillations. In our analysis we have considered the SNe type la Union sample compiled by Kowalski et al. [M. Kowalski et al., Astrophys. J. 686 (2008) 749, arXiv:0804.4142]. At 95.4% (c.l.), we find for BAD + Union sample, alpha = 0.81(-0.04)(+0.04) and Omega(Q4) = 1.15(-0.17)(+0.16) The best-fit for this simplified quartessence scenario is a spatially closed Universe and its reduced chi(2) is exactly the same of the flat concordance model (Lambda CDM). (C) 2009 Elsevier B.V. All rights reserved.

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

Microbiological profile of untreated subjects with localized aggressive periodontitis

Aim The microbial profile of localized aggressive periodontitis (LAgP) has not yet been determined. Therefore, the aim of this study was to evaluate the subgingival microbial composition of LAgP. Material and Methods One hundred and twenty subjects with LAgP (n=15), generalized aggressive periodontitis (GAgP, n=25), chronic periodontitis (ChP, n=30) or periodontal health (PH, n=50) underwent clinical and microbiological assessment. Nine subgingival plaque samples were collected from each subject and analysed for their content of 38 bacterial species using checkerboard DNA-DNA hybridization. Results Red complex and some orange complex species are the most numerous and prevalent periodontal pathogens in LAgP. The proportions of Aggregatibacter actinomycetemcomitans were elevated in shallow and intermediate pockets of LAgP subjects in comparison with those with GAgP or ChP, but not in deep sites. This species also showed a negative correlation with age and with the proportions of red complex pathogens. The host-compatible Actinomyces species were reduced in LAgP. Conclusion A. actinomycetemcomitans seems to be associated with the onset of LAgP, and Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Campylobacter gracilis, Eubacterium nodatum and Prevotella intermedia play an important role in disease progression. Successful treatment of LAgP would involve a reduction in these pathogens and an increase in the Actinomyces species.

Ni-Zn-Sm nanopowder ferrites: Morphological aspects and magnetic properties

Ni-Zn ferrites have been widely used in components for high-frequency range applications due to their high electrical resistivity, mechanical strength and chemical stability. Ni-Zn ferrite nanopowders doped with samarium with a nominal composition of Ni0.5Zn0.5Fe2-xSmxO4 (x = 0.0, 0.05, and 0.1 mol) were obtained by combustion synthesis using nitrates and urea as fuel. The morphological aspects of Ni-Zn-Sm ferrite nanopowders were investigated by X-ray diffraction, nitrogen adsorption by BET, sedimentation, scanning electron microscopy and magnetic properties. The results indicated that the Ni-Zn-Sm ferrite nanopowders were composed of soft agglomerates of nanoparticles with a high surface area (55.8-64.8 m(2)/g), smaller particles (18-20 nm) and nanocrystallite size particles. The addition of samarium resulted in a reduction of all the magnetic parameters evaluated, namely saturation magnetization (24-40 emu/g), remanent magnetization (2.2-3.5 emu/g) and coercive force (99.3-83.3 Oe). (c) 2007 Elsevier B. V. All rights reserved.

Household survey of hepatitis B vaccine coverage among Brazilian children

We conducted a multi-stage household cluster survey to calculate hepatitis B vaccine coverage among children 18-30 months of age in 27 Brazilian cities. Hepatitis B vaccine is administered at birth, 1 month and 6 months of age by Brazil`s national immunization program. Among 17,749 children surveyed, 40.2% received a birth dose within one day of birth, 94.8% received at least one dose of hepatitis B vaccine, and 86.7% completed the three-dose series by 12 months of age. Increased coverage with the birth dose and administration of hepatitis B in combination with diphtheria-tetanus-pertussis-Haemophilus influenzae type b antigens could improve protection against hepatitis B. (C) 2009 Elsevier Ltd. All rights reserved.