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A prospective study was conducted on 79 advanced immunosuppressed AIDS patients from 1997 to 1999, during which nine cases of tuberculosis (TB) were diagnosed. The main clinical and laboratory characteristics and the response to TB treatment were reviewed. The clinical manifestations of TB were: pulmonary (six cases), extrapulmonary (two cases) and disseminated (one case). These patients were being treated with highly active antiretroviral treatment (HAART) and were not responding. In three cases an optional regimen without rifampicin (RMP) was indicated to maintain HAART during TB treatment. A clinical response to TB treatment (disappearance of fever) was observed in 6/9 patients during a mean of 73 days (SD = 96). The three unresponsive patients were those treated without RMP. A switch to TB regimens containing RMP was proposed and successful. In our study, though it was limited by a small sample size, the response to TB regimens without rifampin was poor in immunossupressed patients failing HAART.

Equine infectious anemia (EIA) is listed by the World Organization for Animal Health (OIE) as one of the equine diseases that must be notified. No effective treatment or vaccine is available. EIA control is based on segregation and euthanasia of positive equids. The disease is caused by the equine infectious anemia virus (EIAV), a member of the genus Lentivirus of the Retroviridae family. Despite the importance of this disease in equids, EIA has been poorly studied in donkeys (Equus asinus). We evaluate the sanitary conditions related to EIAV in donkeys from a shelter of abandoned animals captured on the roads of the Ceará. A total of 124 donkeys were randomly selected, and three horses lived at the same shelter. The animals were clinically evaluated, and a group of the 20 animals was submitted to hematological tests. Three diagnostic tests for EIA were used, agar gel immunodiffusion (AGID), enzyme-linked immunosorbent assay (ELISA) using EIAV recombinant protein gp90 (rgp90) and recombinant protein p26 (rp26) ELISA, and polymerase chain reaction (PCR) for detection of the EIAV tat-gag gene. From the donkeys, only 1 animal was positive using AGID 0.81% (1/124), compared to 21.8% (27/124) in the rgp90 and 10.5% (13/124) in the rp26 ELISA. Proviral DNA was detected by PCR tat-gag in 8.8% (11/124), and phylogenetic analysis confirms that the EIAV sequences of donkeys from the Brazilian Northeast grouped with Pantanal Brazilian sequences. Thus, in light of the results, we conclude that donkeys are carriers of EIAV and could be sources of infection., (Copyright © 2021. Published by Elsevier Inc.)

Clinicopathological and imaging studies indicate that metastatic spread of cancer cells through the airways may occur in primary lung cancer. The term aerogenous metastasis was been proposed years before the concept of spread through the airspaces (STAS) was introduced in the current World Health Organization classification. The pathogenesis of STAS has not been fully elucidated. The current definition of STAS is controversial and limited to early stage adenocarcinomas. In this article, existing knowledge on the pathogenesis, histology, imaging findings, and clinical and prognostic significance of these 2 entities is presented., Competing Interests: Disclosure C.A. Souza: Consultant fees and honorarium: Pfizer, Boehringer-Ingelheim, AstraZeneca, Hoffmann-La Roche. Advisory board: AstraZeneca, Boehringer-Ingelheim. Educational Grant: Boehringer-Ingelheim. M.M. Gomes: Educational Grants: Pfizer, BMS, Merck, AstraZeneca, Roche, Eli Lilly, Boehringer-Ingelheim. Honoraria: AstraZeneca, Hoffmann-La Roche., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this review, the authors describe the imaging characteristics of solid and subsolid nodules as well as their management recommendations including the use of image-guided percutaneous biopsy and preoperative coil localization. Using case presentations, they offer practical management tips for the most commonly encountered nodule nodules in a thoracic surgical practice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The implementation of environmental monitoring programs in areas under anthropogenic pressure is essential to investigate the processes that generate and maintain biodiversity in ecosystems and to establish the most appropriate conservation strategies according to the area. We investigated whether environmental variables or temporal scale influenced zooplankton spatial diversity and beta diversity components in the Madeira River basin (Amazon tributary, Rondônia state, Brazil) from 2009 to 2015. We also investigated the local site contribution to overall beta diversity (LCBD) and to each of its components, to be able to propose conservation strategies more suitable for the river basin. Alpha diversity values decreased over time, while total beta diversity and the abundance difference component increased. A pattern of abundance difference (Podani family) dominated spatial beta diversity within the major sampling campaigns (at each time point). Environmental variables and heterogeneity, temporal scale (sampling campaigns), and also the dam installation contributed to variation in spatial beta diversity and its components. On the other hand, the flood pulse did not influence spatial beta diversity over time. Few sites contributed significantly to beta diversity prior dam installation, but most sites contributed significantly to beta diversity values at least at one point in time, in the post-dam phase. Thus, post-damming, all sites should continue to be monitored for conservation and restoration of zooplankton communities and biodiversity preservation, as changes are likely to still occur. Analysis of beta diversity, its components, and LCBD, are useful and efficient methods to study spatio-temporal changes in communities and identify critical sites. Impoundment and environmental variation significantly affect zooplankton community beta diversity, dependent on underlying mechanisms such as substitution or abundance differences that diversify communities spatially and temporally., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of Y-chromosomal genetic markers in forensic investigations demands the establishment of reliable and representative DNA databases of different reference populations. The genetic characterization of the Y chromosome variation in human populations requires the analyses of haplotype frequencies allied to haplogroup determination. The present study aimed to contribute to the Brazilian database by providing 1,382 Yfiler Plus individual profiles, from 11 Brazilian states. The Yfiler Plus markers showed high haplotype diversities in all Brazilian populations (>0.9970), allowing high intra-population discrimination in forensic investigations. Pairwise genetic distances showed a homogeneity between Brazilian populations (F ST ≤ 0.0043; non-differentiation p-values ≥ 0.0212), indicating that admixed populations from Brazil can be represented in a single Yfiler Plus haplotype database, for forensic purposes. The performance of Haplogroup Predictor and NevGen software in haplogroup prediction based on Yfiler Plus and Yfiler haplotypes was evaluated in a subset of 416 Brazilian samples that were also genotyped for 51 Y-SNPs. In 25% of the samples, no classification or errors were found for at least one of the prediction tools or marker sets. NevGen presented lower error rates (5.52% and 8.65% with Yfiler Plus and Yfiler, respectively) than Haplogroup Predictor (16.11% with Yfiler Plus and 13.70% with Yfiler). In conclusion, both haplogroup prediction tools can be useful to direct the SNP typing, but present large error rates to be used in forensic analysis, especially in predicting African haplogroups in admixed South American populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cardiovascular events (CVEs) have been observed in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors., Patients and Methods: We retrospectively evaluated the incidence of CVEs on 233 consecutive patients with chronic myeloid leukemia, of which 116 were treated with imatinib, 75 with dasatinib, and 42 with nilotinib. The median follow-up was 2047, 1712, and 1773 days, respectively., Results: The cumulative incidence of CVEs was 4.29%. Three events occurred during dasatinib treatment, 6 during nilotinib treatment, and none during imatinib treatment (P ≤ .001). Arterial occlusive events occurred in 2 (2.6%) of 75 patients treated with dasatinib and in 6 (14.2%) of 42 patients treated with nilotinib (P ≤ .001). Furthermore, all of them occurred in patients with high-risk (n = 2) and very high-risk (n = 6) cardiovascular risk, contributing to 4.3% of mortality., Conclusion: CVEs were more frequent in patients treated with second-generation tyrosine kinase inhibitors. Arterial occlusive events were more frequent in patients treated with nilotinib, with high and very high cardiovascular risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The prognostic significance of breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) transcripts in chronic myeloid leukemia (CML) is still controversial., Patients and Methods: All consecutive CML patients in chronic phase treated with imatinib in a single center were analyzed (n = 170). BCR-ABL1 transcript was evaluated using multiplex reverse transcription polymerase chain reaction. Exclusively patients with BCR-ABL transcripts e13a2 and/or e14a2 were included in this analysis., Results: Patients with e14a2 transcripts presented higher rates of optimal molecular responses at 3 months and higher rates of complete cytogenetic response (CCR) at 6 months. E13a2, e14a2, and e14a2 with e13a2 (e14a2+e13a2) groups presented similar rates of 5-year event-free, progression-free, and overall survival. There was a superior 10-year overall survival in patients with transcripts e13a2 compared with e14a2 (alone or coexpressed with e13a2; 93% vs. 73%; P = .03), although the 5-year overall survival was 96% vs. 88%, respectively (P = not significant). In a multivariate analysis, high/intermediate Sokal score and e14a3/e14a3+e14a2 were independent factors for poor overall survival (hazard risk [HR], 4.63; P = .023 for Sokal score and HR, 10.6; P = .041 for BCR-ABL transcript)., Conclusion: Patients with BCR-ABL transcripts e14a2 transcripts have higher rates of CCR at 6 months and higher rates of optimal molecular response at 3 months compared with e13a2 or with both transcripts, but no difference in 5-year overall, progression-free, and event-free survival. There was a superior 10-year overall survival among patients with transcripts e13a2 compared with e14a2 (alone or coexpressed with e13a2)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Globally, there is a lack of knowledge about tropical ecotoxicology dealing with the potential impact of metal contamination in mangrove ecosystem. This habitat is considered a nursery for several animal species, among them the "uçá"-crab (Ucides cordatus), known as a key species due to its biological and economical importance. This study evaluated the association involving metal contamination (Cd, Cu, Pb, Cr, Mn and Hg) in water, sediment, red-mangrove vegetation (Rhizophora mangle) and tissues of uçá crab, together with its geno-cytotoxic responses, based on micronucleated hemocytes frequency and the retention time of neutral red in lysosomes. We assessed six mangrove areas with distinct pollution levels in São Paulo State, Brazil, where the water and sediment contamination by metals were associated with accumulation of these pollutants in biotic compartments (mangrove leaves and crab). In U. cordatus, metal accumulation was best explained by metal concentration found in leaves of R. mangle than in the water or sediment, indicating that feeding drives metal exposure in this organism. Mercury (Hg) concentration in sediment, copper (Cu) concentration in hepatopancreas of U. cordatus and lead (Pb) in water and green leaves of R. mangle showed a significant correlation with genotoxic impact in U. cordatus. However, copper concentration (in green/senescent leaves and hepatopancreas) and lead (in sediment), were the major metals affecting lysosomal membrane integrity. Therefore, representatives of all compartments were associated with cyto and genotoxicity in this species, thus requiring a holistic approach to issues related to sublethal damage. Probability estimates of cytogenetic impacts related to metal concentration in abiotic compartments (significantly correlated with known biomarkers: Hg in sediment; and Pb in water and sediment) are also presented. Our results highlight the need for environmental restoration of mangroves areas contaminated with metals, responsible for cytogenetic injuries and revealing a pre-pathological condition in this sentinel species, in addition to ecological disturbances., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Despite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkin's lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil., Methods: A 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment., Results: Thirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients., Conclusion: Everolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkin's lymphoma who had adequate tolerability to the drug., (Copyright © 2017 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aero-digestive tract caused by human papillomavirus (HPV) infection, which affects children and young adults. The aim of this review is to describe the main etiological, epidemiological, clinical, diagnostic, and treatment aspects of RRP. Most infections in children occur at birth, during passage through the birth canals of contaminated mothers. In adults, HPV is transmitted sexually. Papillomas usually appear as exophytic nodules, primarily in the larynx, but occasionally involving the nasopharynx, tracheobronchial tree, and pulmonary parenchyma. The disease course is unpredictable, ranging from spontaneous remission to aggressive persistent or recurrent disease. Although it occurs rarely, RRP has the potential for malignant transformation to squamous cell carcinoma. Clinically, RRP usually presents with nonspecific symptoms of airway involvement, including chronic cough, hoarseness, wheezing, voice change, stridor, and chronic dyspnea. Helical computed tomography (CT) is highly accurate for the identification and characterization of focal or diffuse airway narrowing caused by nodular vegetant lesions. The typical CT pattern of lung papillomatosis consists of numerous multilobulated nodular lesions of various sizes, frequently cavitated, scattered throughout the lungs. Bronchoscopy is the most reliable method for the diagnosis of RRP; it enables direct visualization of lesions in the central airways and collection of biopsy samples for histopathological diagnosis, and is also useful for therapeutic planning. The definitive diagnosis of RRP is based on histopathological analysis. Currently, no definitive curative treatment for RRP is available; despite the availability of adjunctive treatments, surgery remains the mainstay of treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to perform a critical review of the literature that investigated the association between diabetes and apical periodontitis., Methods: An electronic search was performed on PubMed/MEDLINE, LILACS, Scientific Electronic Library Online (Scielo), and Cochrane Collaboration databases. Human studies assessing the effect of diabetes in apical periodontitis development or in healing after root canal treatment were included. The outcome was apical periodontitis., Results and Conclusions: Nine articles were included. The results presented in the literature to date are still scarce and incipient, and the evidence for such an association is not yet conclusive. However, the published results trend to converge on a positive association between diabetes and a larger number of periapical lesions., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The persistent organic pollutants (POPs), such as organochlorine pesticides and PCBs, are ordinarily monitored in the aquatic environment or in soil in the environmental quality monitoring programs in São Paulo, Brazil. One of the core matrices proposed in the POPs Global Monitoring Plan (GMP) from the Stockholm Convention list is the ambient air, which is not a usual matrix for POPs monitoring in the country. In this study POP levels were evaluated in the air samples from an urban site in São Paulo City over five years, starting in 2010 as a capacity building project for Latin America and the Caribbean region for POP monitoring in ambient air using passive samplers. Furthermore, after the end of the Project in 2012, the monitoring continued in the same sampling site as means to improving the analytical capacity building and contribute to the GMP data. The POPs monitored were 17 congeners of 2,3,7,8 chloro-substituted PCDDs and PCDFs, dioxin-like PCBs, indicator PCBs, organochlorine pesticides and toxaphene. The results show a slight decrease in PCDD/F, dl-PCBs and indicator PCBs levels along the five years. The organochlorine pesticide endosulfan was present at its highest concentration at the beginning of the monitoring period, but it was below detection level in the last year of the monitoring. Some other organochlorine pesticides were detected close to or below quantitation limits. The compounds identified were dieldrin, chlordane, α-HCH, γ-HCH, heptachlor, heptachlor epoxide, hexachlorobenzene and DDTs. Toxaphene congeners were not detected. These results have confirmed the efficacy of passive sampling for POP monitoring and the capacity building for POP analysis and monitoring was established. However more needs to be done, including expansion of sampling sites, new POPs and studies on sampling rates to be considered in calculating the concentration of POPs in ambient air using a passive sampler., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is a global lack of knowledge on tropical ecotoxicology, particularly in terms of mangrove areas. These areas often serve as nurseries or homes for several animal species, including Ucides cordatus (the uçá crab). This species is widely distributed, is part of the diet of human coastal communities, and is considered to be a sentinel species due to its sensitivity to toxic xenobiotics in natural environments. Sublethal damages to benthic populations reveal pre-pathological conditions, but discussions of the implications are scarce in the literature. In Brazil, the state of São Paulo offers an interesting scenario for ecotoxicology and population studies: it is easy to distinguish between mangroves that are well preserved and those which are significantly impacted by human activity. The objectives of this study were to provide the normal baseline values for the frequency of Micronucleated cells (MN‰) and for neutral red retention time (NRRT) in U. cordatus at pristine locations, as well to indicate the conservation status of different mangrove areas using a multi-level biological response approach in which these biomarkers and population indicators (condition factor and crab density) are applied in relation to environmental quality indicators (determined via information in the literature and solid waste volume). A mangrove area with no effects of impact (areas of reference or pristine areas) presented a mean value of MN‰<3 and NRRT>120min, values which were assumed as baseline values representing genetic and physiological normality. A significant correlation was found between NRRT and MN, with both showing similar and effective results for distinguishing between different mangrove areas according to conservation status. Furthermore, crab density was lower in more impacted mangrove areas, a finding which also reflects the effects of sublethal damage; this finding was not determined by condition factor measurements. Multi-level biological responses were able to reflect the conservation status of the mangrove areas studied using information on guideline values of MN‰, NRRT, and density of the uçá crab in order to categorize three levels of human impacts in mangrove areas: PNI (probable null impact); PLI (probable low impact); and PHI (probable high impact). Results confirm the success of U. cordatus species' multi-level biological responses in diagnosing threats to mangrove areas. Therefore, this species represents an effective tool in studies on mangrove conservation statuses in the Western Atlantic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The clinical course of gastric lymphoma is heterogeneous and clinical symptoms and some factors have been related to prognosis., Objective: The present study aims to identify prognostic factors in gastric diffuse B-cell non-Hodgkin lymphoma diagnosed and treated in different countries., Methods: A consecutive series of gastric diffuse B-cell non-Hodgkin lymphoma patients diagnosed and treated in Brazil, Portugal and Italy, between February 2008 and December 2014 was evaluated., Results: Of 104 patients, 57 were female and the median age was 69 years (range: 28-88). The distribution of the age-adjusted international prognostic index was 12/95 (13%) high risk, 20/95 (21%) high-intermediate risk and 63/95 (66%) low/low-intermediate risk. Symptoms included abdominal pain (63/74), weight loss (57/73), dysphagia (37/72) and nausea/vomiting (37/72). Bulky disease was found in 24% of the cases, anemia in 33 of 76 patients and bleeding in 22 of 72 patients. The median follow-up time was 25 months (range: 1-77 months), with 1- and 5-year survival rates of 79% and 76%, respectively. The multivariate Cox Regression identified the age-adjusted international prognostic index as a predictor of death (hazard risk: 3.62; 95% confidence interval: 2.21-5.93; p-value <0.0001)., Conclusions: This series identified the age-adjusted international prognostic index as predictive of mortality in patients treated with conventional immunochemotherapy., (Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Fat embolism syndrome (FES) is a rare but potentially fatal complication of trauma or orthopedic surgery, which presents predominantly with pulmonary symptoms. Modern intensive care has improved the mortality rates, however diagnosis remains difficult, relying predominantly on a combination of a classic triad of symptoms and non-specific, but characteristic radiological features. The aim of this review is to describe the main clinical and imaging aspects of FES, ranging from pathophysiology to treatment with emphasis on pulmonary involvement., Methods: We reviewed the currently published literature on the main characteristics of FES., Results: In a hypoxic patient with recent trauma or orthopedic surgery, the presence of diffuse, well-demarcated ground glass opacities or ill-defined centrilobular nodules on computed tomography (CT) of the chest are suggestive of FES., Conclusions: Combination of the classic clinical syndrome in the appropriate clinical setting, together with the characteristic imaging findings on chest CT, can help to achieve the correct diagnosis. Management remains predominantly supportive care, and the benefit of medical therapies such as corticosteroids and heparin remains unclear., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Water is a key ingredient in the creation and sustainment of life. Moreover, water may be a key vehicle in the processes of energy healing, such as in the preparation of homeopathic remedies and spiritual treatments. Given these properties, the purpose of this study was to investigate whether the application of Johrei to water could lead to significant changes in the hydrodynamic behaviour of the fluid., Methods: Four regular Johrei practitioners (P1, P2, P3 and P4) were selected for this study. Dripping water produced at the tip of a capillary was used as the hydrodynamic behaviour model. This behaviour was modelled mathematically, and tuning parameters φ4 and τ were used to assess significant differences in the dripping water samples that were subjected to Johrei compared with the samples that were not so treated. The tuning parameters were obtained using the Levenberg-Marquardt fitting algorithm. The data sets for each Johrei practitioner and the control experiment were analysed using ANOVA and a paired t-test., Results: The mathematical model exhibited an excellent fit to our data, generating correlation coefficients (r) greater than or equal to 0.999. Significant differences were observed in both τ (P1 and P2, P < 0.05 and P < 0.01, respectively) and φ4 (P2, P < 0.01). As expected, no significant difference for the control experiment (without Johrei) was observed., Conclusions: Our results indicated a statistically significant change in the hydrodynamic behaviour of water correlated with Johrei treatment for 50% of the participating Johrei practitioners., (Copyright © 2015. Published by Elsevier Inc.)

Objective: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib., Methods: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing., Results: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months., Conclusions: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

Objectives: To evaluate the short-term response of human pulps to ethanol-wet bonding technique., Methods: Deep class V cavities were prepared on 17 sound premolars and divided into three groups. After acid-etching, the cavities from groups 1 (G1) and 2 (G2) were filled with 100% ethanol or distilled water, respectively, for 60 s before the application of Single Bond 2. In group 3 (G3, control), the cavity floor was lined with calcium hydroxide before etching and bonding. All cavities were restored with resin composite. Two teeth were used as intact control. The teeth were extracted 48h after the clinical procedures. From each tooth serial sections were obtained and stained with haematoxylin and eosin (H/E) and Masson's trichrome. Bacteria microleakage was assessed using Brown & Brenn. All sections were blindly evaluated for five histological features., Results: Mean remaining dentine thickness was 463±65μm (G1); 425±184μm (G2); and 348±194μm (G3). Similar pulp reactions followed ethanol- or water-wet bonding techniques. Slight inflammatory responses and disruption of the odontoblast layer related to the cavity floor were seen in all groups. Stained bacteria were not detected in any cavities. Normal pulp tissue was observed in G3 except for one case., Conclusions: After 48h, ethanol-wet bonding does not increase pulpal damage compared to water-wet bonding technique., Clinical Significance: Ethanol-wet bonding may increase resin-dentine bond durability. This study reported the in vivo response of human pulp tissue when 100% ethanol was applied previously to an etch-and-rinse simplified adhesive system., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare, inherited autosomal-dominant disorder characterized by the development of cutaneous lesions, renal tumors, pulmonary cysts, and spontaneous pneumothorax. The gene responsible for BHDS is located on the short arm of chromosome 17 (17p11.2) and codes for the protein folliculin, which is believed to be an oncogene suppressor protein., Methods: We reviewed currently published literature on the main characteristics of BHDS., Results: Pulmonary cysts and spontaneous pneumothorax are often the presenting manifestations that lead to a final diagnosis in family members affected by the syndrome., Conclusions: Certain imaging characteristics of pulmonary cysts, including size and location, can suggest the diagnosis of BHDS based on chest computed tomography alone. The main concern in patients with BHDS is the increased risk of renal carcinoma. The aim of this review is to describe the main pathological, clinical, and imaging aspects of BHDS, ranging from its genetic basis to treatment, with emphasis on pulmonary involvement., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to evaluate the effects of infrared LED (850nm) irradiation on dentin matrix proteins expression and synthesis by cultured stem cells from human exfoliated deciduous teeth (SHED)., Methods: Near-exfoliation primary teeth were extracted (n=3), and SHED cultures were characterized by immunofluorescence using STRO-1, CD44, CD146, Nanog and OCT3/4 antibodies, before experimental protocol. The SHEDs were seeded (3×10(4) cells/cm(2)) with DMEM containing 10% FBS. After 24-h incubation, the culture medium was replaced by osteogenic differentiation medium, and the cells were irradiated with LED light at energy densities (EDs) of 0 (control), 2, or 4J/cm(2) (n=8). The irradiated SHEDs were then evaluated for alkaline phosphatase (ALP) activity, total protein (TP) production, and collagen synthesis (SIRCOL™ Assay), as well as ALP, collagen type I (Col I), dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein (DMP-1) gene expression (qPCR). Data were analyzed by Kruskal-Wallis and Mann-Whitney tests (α=0.05)., Results: Increased ALP activity and collagen synthesis, as well as gene expression of DSPP and ALP, were observed for both EDs compared with non-irradiated cells. The ED of 4J/cm(2) also increased gene expression of COL I and DMP-1., Conclusions: In conclusion, infrared LED irradiation was capable of biostimulating SHEDs by increasing the expression and synthesis of proteins related with mineralized tissue formation, with overall better results for the energy dose of 4J/cm(2)., Clinical Significance: Phototherapy is an additional approach for the clinical application of LED in Restorative Dentistry. Infrared LED irradiation of the cavity's floor could biostimulate subjacent pulp cells, improving local tissue healing., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABL(IS)] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABL(IS) >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497.

Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT., Methods: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed., Results: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure., Conclusion(s): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.

Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Despite recent advances in treatment modalities, the survival rate of patients with lung cancer has not significantly improved. Therefore, new avenues are being explored in the era of evolving personalized patient management by early detection. Cytology is now the mainstay to address the diagnostic needs of pulmonary malignancies. Cytology specimens deliver diagnostic results equivalent to tissue biopsies. Fine-needle aspirations are equally useful to perform diagnostic, predictive, and prognostic immunohistochemical markers and molecular analysis. This article reviews the main new technologies that produced this revolution. The new role of the cytopathologist in this time of interdisciplinary care is also discussed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The aim of the present study was to assess the bond strength of root fillings in oval-shaped canals prepared with the self-adjusting file (SAF) system., Methods: A careful specimen selection resulted in 2 equal groups, each consisting of 12 extracted mandibular canines with oval canals that had vital pulps before extraction. One group was subjected to the SAF protocol, and the other group underwent conventional protocol, which was the ProTaper system with syringe-needle irrigation. Full-strength sodium hypochlorite was used as an irrigant for both groups. The teeth were obturated in a standardized way, filled with a lentulo spiral as the root filling, and then prepared for micropush-out assessment by using root slices of 1-mm thickness. Loading was performed on a universal testing machine at a speed of 0.5 mm/min(-1). The Student's t test for pairwise comparisons was applied to assess the effect of each preparation technique on the push-out bond strength., Results: All specimens showed measurable adhesive properties to root dentin. In addition, no premature failure occurred. The group-by-location interaction was significant (P = .0071); thus, the group comparisons were dependent on the canal third. Overall, the push-out bond strength was the highest in the coronal third and the lowest in the apical third. SAF-prepared specimens displayed significantly higher bond strengths (P = .0012, 0.51-5.9 MPa)., Conclusions: The present study showed that SAF preparation markedly influenced root-filling push-out bond strength in oval-shaped canals. Further investigations are needed to provide a better understanding of the physicochemical modifications of the root dentin prepared with the SAF cleaning-shaping-irrigation system., (Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome., Methods: A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival., Results: A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS- low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02)., Conclusions: These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.

Introduction: The aim of this study was to evaluate the ex vivo effects of root canal preparation, filling techniques, and mechanical cycling (MC) on the incidence of dentin defects and vertical root fractures (VRFs)., Methods: Seventy extracted single-rooted teeth were divided into 6 groups. The first 2 groups were the unprepared and unprepared/MC groups. The other groups were prepared by using Gates Glidden drills and ProTaper Universal files up to F3 and were grouped according to the following: prepared teeth and the absence of root canal filling, passive technique, lateral compaction, and Tagger's hybrid technique. All of the groups except the unprepared group were subjected to MC (1,000,000 cycles, 90 N, 4 Hz, 37°C). The roots were then sectioned horizontally at 3, 6, and 9 mm from the apex and observed under a ×10 stereomicroscope. The defects were categorized as no defect, vertical root fracture, and other defects. The differences between the groups were analyzed by using the Fisher exact and χ(2) tests., Results: MC by itself did not influence the incidence of dentinal defects (P > .05, between the unprepared and unprepared/MC groups). The filled groups presented a similar incidence of other defects (P > .05), although VRFs were observed only when the MC was associated with pressure filling techniques (the lateral compaction and Tagger's hybrid groups)., Conclusions: MC by itself did not induce VRF. When associated with apical pressure filling techniques, however, VRF occurred in 13.3% (lateral compaction) and 33.3% (Tagger's hybrid) of the cases., (Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the high-resolution CT (HRCT) scan findings of patients with the reversed halo sign (RHS) and to identify distinguishing features among the various causes., Methods: Two chest radiologists reviewed the HRCT scans of 79 patients with RHS and determined the CT scan findings by consensus. We studied the morphologic characteristics, number of lesions, and presence of features associated with RHS., Results: Forty-one patients presented with infectious diseases (paracoccidioidomycosis, TB, zygomycosis, invasive pulmonary aspergillosis, Pneumocystis jiroveci pneumonia, histoplasmosis, cryptococcosis), and 38 presented with noninfectious diseases (cryptogenic organizing pneumonia, pulmonary embolism, sarcoidosis, edema, lepidic predominant adenocarcinoma [formerly bronchiolo-alveolar carcinoma], granulomatosis with polyangiitis [Wegener]). The RHS walls were smooth in 58 patients (73.4%) and nodular in 21 patients (26.6%). Lesions were multiple in 40 patients (50.6%) and single in 39 patients (49.4%)., Conclusion: The presence of nodular walls or nodules inside the halo of the RHS is highly suggestive of granulomatous diseases.

Objectives: To investigate the effectiveness of respiratory physiotherapy based on clinical evidence and analyze the improvement in respiratory parameters., Methods: A prospective study was carried out in the Bone Marrow Transplant Unit of the Universidade Estadual de Campinas (UNICAMP). Two different previously established respiratory physiotherapy protocols were applied from days D-1 to D+7 that aimed to improve airway clearance, pulmonary re-expansion and the strengthening of respiratory muscles. Group A were subjected to diaphragmatic proprioceptive stimulation, breathing exercises, incentive spirometry with Respiron(®), inspiratory muscle training with the Threshold(®) Inspiratory Muscle Training device, bronchial hygienization with Shaker(®) and cough stimulation. Group B performed a protocol that only used incentive spirometry. The parameters analyzed were: tidal volume, minute volume, maximal inspiratory pressure, maximal expiratory pressure, oxygen saturation, heart rate and respiratory frequency., Results: Sixty-seven patients submitted to myeloablative hematopoietic stem cell transplantation were included in this study. Among these, thirty-nine were evaluated and randomized in the two groups. There were significant differences between the groups for tidal volume at D+2 (p-value = 0.007) and maximal inspiratory pressure (p-value = 0.03), maximal expiratory pressure (p-value = 0.03) and tidal volume (p-value = 0.004) at D+7., Conclusions: On comparing Group A with Group B, the authors concluded that the protocol of respiratory physiotherapy applied in this study resulted in an improvement in ventilation and in respiratory muscle strength of patients submitted to hematopoietic stem cell transplantation.

Chronic myeloproliferative diseases without the Philadelphia chromosome marker (Ph-), although first described 60 years ago, only became the subject of interest after the turn of the millennium. In 2001, the World Health Organization (WHO) defined the classification of this group of diseases and in 2008 they were renamed myeloproliferative neoplasms based on morphological, cytogenetic and molecular features. In 2005, the identification of a recurrent molecular abnormality characterized by a gain of function with a mutation in the gene encoding Janus kinase 2 (JAK2) paved the way for greater knowledge of the pathophysiology of myeloproliferative neoplasms. The JAK2 mutation is found in 90-98% of polycythemia vera and in about 50% essential thrombocytosis and primary myelofibrosis. In addition to the JAK2 mutation, other mutations involving TET2 (ten-eleven translocation), LNK (a membrane-bound adaptor protein); IDH1/2 (isocitrate dehydrogenase 1/2 enzyme); ASXL1 (additional sex combs-like 1) genes were found in myeloproliferative neoplasms thus showing the importance of identifying molecular genetic alterations to confirm diagnosis, guide treatment and improve our understanding of the biology of these diseases. Currently, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia and mastocytosis are included in this group of myeloproliferative neoplasms, but are considered different situations with individualized diagnostic methods and treatment. This review updates pathogenic aspects, molecular genetic alterations, the fundamental criteria for diagnosis and the best approach for each of these entities.

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.

Study Objective: To demonstrate the prevalence of endometriosis in the intrapelvic portion of the round ligaments of the uterus (RLUs) and to propose criteria for their excision., Design: Retrospective case series analysis of women undergoing laparoscopy for the treatment of deep infiltrating endometriosis (Canadian Task Force classification II-3)., Setting: Tertiary referral hospital., Patients: We evaluated 174 patients who underwent laparoscopy for the treatment of deep infiltrating endometriosis (DIE) between April 2006 and May 2009., Interventions: All patients underwent laparoscopy for the treatment of DIE and had their RLUs removed when there was shortening, deviation, or thickening. After removal, the RLUs were sent for histopathologic analysis to verify the presence or absence of endometriosis., Measurements and Main Results: The prevalence of endometriosis in the RLUs and the association between the macroscopic alterations and the anatomic pathology results were determined. After the identification of macroscopic alterations, 1 or both RLUs (for a total of 42) were removed from 27 of the 174 patients who underwent laparoscopy. The positive predictive value (PPV) of the macroscopic criteria proposed for endometriosis of the RLU was 83.3% (95% confidence interval [CI] = 72.1%-94.5%), with 35 positive RLUs out of the 42 that were excised. The prevalence of endometriosis of the RLU was 13.8% (95% CI = 8.7%-18.9%), with 24 patients having a positive histopathologic examination result for endometriosis., Conclusions: The prevalence of RLU endometriosis in patients with DIE was 13.8%, which emphasizes that a rigorous evaluation of this structure must be part of the routine surgical treatment of patients with endometriosis., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To perform a function evaluation of patients before and after hematopoietic stem cell transplantation., Methods: From November 2008 to November 2010, 29 female (58%) and 21 male patients (42%) with median age of 48 years (range: 24-67) were enrolled in this study. Data collection was performed before and after autologous or allogeneic hematopoietic stem cell transplantation. Evaluation instruments included the 2-minute walking test to evaluate gait performance with assessment of the oxygen saturation, heart rate and Borg Scale before and after the test; grip strength for strength evaluation, Schober Test for spine mobility testing and maximum and adapted activity scores of the Human Activity Profile questionnaire to test functionality in daily activities., Results: Fifty patients were evaluated at baseline; six did not undergo hematopoietic stem cell transplantation (three died, one refused and two were excluded). Thus 44/50 (88% - 21 allogeneic and 23 autologous) transplantations were performed. Only 33 of the 44 patients (75%) performed evaluations after transplantation (nine died and two were excluded). Of the patients who performed both evaluations, significantly lower values were found in the evaluation after transplantation for the 2-minute walking test (p-value = 0.004), grip strength of both right and left hands (p-value = 0.004 and p-value < 0.0001, respectively), the Schober Test, and maximum and adapted activity scores (p-value < 0.0001). The heart rate was higher (p-value = 0.01) before the 2-minute walking test and oxygen saturation was higher (p-value = 0.02) after., Conclusion: Statistical differences indicate functional impairment after transplantation showing physical losses in this population.

The kinetic of chlorhexidine digluconate (CHXDG) uptake from aqueous solution by hydroxyapatite (HA) was investigated by ultraviolet (UV) analysis performed in HA powder (UV-solid) after the CHX adsorption. Adsorption isotherm of chlorhexidine (CHX) uptake was modeled by a combination of Languimir and Langmuir-Freundlich mechanisms. Strong molecule-molecule interactions and positive cooperativity predominated in the surface when CHX concentration was above 8.6 μg(CHX)/mg(HA). UV-solid spectra (shape, intensity and band position) of CHX bound to HA revealed that long-range molecular structures, such as aggregates or micelles, started to be formed at low CHX concentrations (1.52 μg(CHX)/mg(HA)) and predominated at high concentrations. Grazing-incidence X-ray diffraction (GIXRD) analysis from synchrotron radiation discarded the formation of crystalline structures on HA surface or precipitation of CHX crystalline salts, as suggested in previous works. The effect of the HA/CHX association on HA in vitro bioactivity, cytotoxicity and CHX antimicrobial activity was evaluated. It was shown that CHX did not inhibit the precipitation of a poorly crystalline apatite at HA/CHX surface after soaking in simulating body fluid (SBF). Cell viability studies after exposure to extracts of HA and HA/CHX showed that both biomaterials did not present significant in vitro toxicity. Moreover, HA/CHX inhibited Enterococcus faecalis growth for up to 6 days, revealing that binding to HA did not affect antimicrobial activity of CHX and reduced bacterial adhesion. These results suggested that HA/CHX association could result in a potential adjuvant antimicrobial system for clinical use., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Imatinib mesylate was the first BCR-ABL-target agent approved for the treatment of chronic myeloid leukemia. Although most patients respond well to imatinib therapy, the literature shows that one third develops resistance or intolerance. The timing of second-line treatment after failure of initial treatment may have a significant impact on long-term outcome. Thus, appropriate monitoring to identify resistance and/or intolerance is crucial to early intervention with second generation tyrosine kinase inhibitors and attainment of better results.

Objective: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population., Methods: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m(2)) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m(2)) and methotrexate (8 g/m(2) only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation., Results: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13%) and 10 (9%) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups., Conclusions: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality.

Background: Real time PCR has become the most common technique to monitor BCR-ABL transcript levels of patients treated with kinase inhibitors. The aim of this study was to evaluate BCR-ABL levels of chronic myeloid leukemia patients treated with imatinib in the chronic phase and correlate the response to therapy and event-free survival., Methods: BCR-ABL levels were measured in peripheral blood cell samples using Real time PCR at diagnosis and then every 3 months after starting therapy with imatinib. Major molecular response was defined as a three-log reduction from the standardized baseline value. Major molecular response values were adjusted to international scale using a conversion factor of 1.19. The results are reported as a BCR-ABL/ABL ratio (%)., Results: Hematological, major cytogenetic and complete cytogenetic responses were achieved by 57 (95%), 45 (75%) and 38 (63%) patients, respectively. Twenty-four out of sixty patients achieved a major molecular response (40%) in a median time of 8.5 months. Overall survival and event free survival were higher for patients with (100%) versus patients without (77%) a complete cytogenetic response (p-value = 0.01) at 48 months. Patients with complete cytogenetic response and major molecular response had a higher event free survival compared to patients with complete cytogenetic response but without major molecular response (p-value = 0.007)., Conclusion: In conclusion, the prognostic impact of achieving complete cytogenetic response and a major molecular response and also the importance of molecular monitoring in the follow-up of chronic myeloid leukemia patients were demonstrated.s.

Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.