Background: The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1-2 mutation are poorly known.

To assess the impact of highly active antiretroviral therapy (HAART) on the outcome of systemic human immunodeficiency virus-related non-Hodgkin lymphoma (HIV-NHL), we retrospectively analyzed 235 patients in whom HIV-NHL was diagnosed from April 1988 through December 1999. A multivariate Cox proportional hazards model was used to estimate prognostic factors for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Complete remission occurred in 49% of patients, and the 3-year rates of OS, PFS, and DFS were 19%, 49%, and 73%, respectively. The greatest risk for shortened OS, PFS, and DFS was associated with no HAART use (compared with long-term HAART use); hazard ratios were 17.42 (95% confidence interval [CI], 17.42-40.25), 9.11 (95% CI, 3.71-22.32), and 8.54 (95% CI, 1.19-61.11), respectively. Our study suggests that the long-term use of HAART may favorably change the outcome for patients with systemic HIV-NHL.

A total of 28 patients were treated with mitoxantrone, vinorelbine and prednisone every 3 weeks. In all, 11 patients (46%) had a significant prostate-specific antigen decline for a median duration of 11.4 months. Eight patients (33%) achieved a partial response on pain, while seven (29%) obtained a stabilisation of the symptom. Median duration of the response was 9.5 months. A confirmed partial response was obtained in three out of seven patients who had bidimensionally measurable disease. Toxicity was manageable. Our study provides further support to the concept of combined antimicrotubule therapy for metastatic harmonoresistant prostate cancer, promoting the exploration of new regimens containing antimicrotubule agents in addition to mitoxantrone-prednisone.

Um cão da raça Poodle, de 11 anos de idade foi encaminhado ao Hospital Veterinário da Universidade Federal do Paraná (UFPR), com histórico de hiporexia e emagrecimento há seis meses. No exame físico constatou-se caquexia, mucosas hipocoradas e ausência de febre. No hemograma observou-se anemia, leucocitose, neutrofilia extrema e desvio nuclear dos neutrófilos à esquerda (101.200 leucócitos/µL; 87.032 segmentados/µL; 4.048 bastonetes/µL). No exame da medula óssea observou-se hiperplasia mielóide sem evidências de leucemia, confirmando a ocorrência de reação leucemóide. A ultra-sonografia abdominal identificou estrutura de 3,43 cm em alças intestinais, sugestiva de neoplasia mural de segmento piloro-duodenal. Realizou-se a exérese cirúrgica. O tumor foi identificado como neoplasia maligna de origem mesenquimal no exame histopatológico. No pós-operatório observou-se apetite normal do cão e a resolução das anormalidades hematológicas (6.348 neutrófilos/µL; 0 bastonetes/µL). O presente trabalho descreve um caso de reação leucemóide paraneoplásica com resolução das anormalidades após a remoção da neoplasia.

The addition of cytokines, such as interferon alpha-2b and interleukin-2, to chemotherapy in metastatic melanoma has produced conflicting results in phase II and III trials. We report our experience with a chemoimmunotherapeutic regimen using subcutaneous cytokines. Twenty-eight patients with advanced melanoma (median age, 45 years; male to female ratio, 19 : 9) were treated. Doses were as follows: cisplatin, 20 mg/m intravenously (iv) days 1-4; vinblastine, 1.6 mg/m iv days 1-4; dacarbazine, 800 mg/m iv day 1; interferon alpha-2b, 5 MIU/m subcutaneously (sc) days 1-5; interleukin-2, 9 MIU/m sc days 1-5 and 8-12. Treatment was repeated every 3 weeks for a maximum of six cycles. The response was assessed after two cycles and toxicity at every cycle, according to World Health Organization (WHO) and National Cancer Institute (NCI) criteria, respectively. At a median follow-up of 8 months, only four patients (14%) were still alive. The overall response rate was 33%, with three (11%) complete responses lasting for 17, 14 and >24 months. There were six (22%) partial responses and three stable disease. Amongst the responders, three patients progressed at the level of the central nervous system. The median time to progression and overall survival were 3.5 and 9 months, respectively. The most common grade 3-4 toxicity was neutropenia, reported in 25 of the 28 patients (92%). Only two patients (7%) experienced neutropenic fever. Thrombocytopenia grade 3-4 occurred in seven of the 28 patients (25%), with only one patient needing transfusional support. One toxic death due to neutropenic fever occurred. It can be concluded that the chemoimmunotherapy schedule evaluated is active and may be considered for patients with metastatic melanoma who have a good performance status and a limited disease burden.

<p>It is well known that for earthquake-generated tsunamis impacting near-field coastlines the focal mechanism, the position of the fault with respect to the coastline and the on fault slip distribution are key factors in determining the efficiency of the generation process and the distribution of the maximum run-up and inundation along the nearby coasts. The time needed to obtain the aforementioned information from the analysis of seismic records is usually too long compared to the time required to issue a timely tsunami warning/alert to the nearest coastlines. In the context of tsunami early warning systems, a big challenge is hence to be able to define 1) the relative position of the hypocenter and of the fault and 2) the earthquake focal mechanism, based only on the preliminary earthquake localization and magnitude estimation, which are made available by seismic networks soon after the earthquake occurs.</p><p>In this study, the intrinsic unpredictability of the position of the hypocenter on the fault plane is studied through a probabilistic approach based on the analysis of two finite fault model datasets (SRCMOD and USGS) and by limiting the analysis to moderate-to-large shallow earthquakes (Mw  6 and depth  50 km). After a proper homogenization procedure needed to define a common geometry for all samples in the two datasets, the hypocentral positions are fitted with different probability density functions (PDFs) separately in the along-dip and along-strike directions.</p><p>Regarding the focal mechanism determination, different approaches have been tested: the most successful is restricted to subduction-type earthquakes. It defines average values and uncertainties for strike, dip and rake angles based on a combination of a proper zonation of the main tsunamigenic subduction areas worldwide and of subduction zone geometries available from publicdatabases.</p><p>The general workflow that we propose can be schematically outlined as follows. Once an earthquake occurs and the magnitude and hypocentral solutions are made available by seismic networks, it is possible to assign the focal mechanism by selecting the characteristic values for strike, dip and rake of the zone where the hypocenter falls into. Fault length and width, as well as the slip distribution on the fault plane, are computed through regression laws against magnitude proposed by previous studies. The resulting rectangular fault plane can be discretized into a matrix of subfaults: the position of the center of each subfault can be considered as a “realization” of the hypocenter position, which can then be assigned a probability. In this way, we can define a number of earthquake fault scenarios, each of which is assigned a probability, and we can run tsunami numerical simulations for each scenario to quantify the classical observables, such as water elevation time series in selected offshore/coastal tide-gauges, flow depth, run-up, inundation distance. The final results can be provided as probabilistic distributions of the different observables.</p><p>The general approach, which is still in a proof-of-concept stage, is applied to the 16 September 2015 Illapel (Chile) tsunamigenic earthquake (Mw = 8.2). The comparison with the available tsunami observations is discussed with special attention devoted to the early-warning perspective.</p>

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