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A hipertensao arterial e considerada um dos principais fatores de risco para o desenvolvimento de doencas cardiovasculares. Dentre as estrategias de prevencao, controle e tratamento da hipertensao arterial, o treinamento aerobio se apresenta como uma ferramenta efetiva, responsavel por quedas cronicas dos niveis de pressao arterial, sendo recomendado por diretrizes internacionais de hipertensao. No entanto, ainda que recomendacoes internacionais corroborem os efeitos anti-hipertensivos do exercicio fisico para a maioria dos individuos, as respostas individuais ao treinamento regular podem ser altamente heterogeneas, havendo individuos nao-responsivos a intervencao. A investigacao dos fatores relacionados a heterogeneidade de resposta da pressao arterial ao treinamento aerobio pode contribuir para a adocao de estrategias de treinamento mais eficientes, garantindo beneficios a um maior numero de individuos.

none 11 no BACKGROUND: Experts and scientific society guidelines recommend that rapid on-site evaluation (ROSE) be used with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to optimize lung cancer genotyping, but no comparative trial has been carried out to confirm and quantify its usefulness. METHODS: To assess the influence of ROSE on the yield of EBUS-TBNA for a multigene molecular analysis of lung cancer samples, consecutive patients with suspected or known advanced lung cancer were randomized to undergo EBUS-TBNA without ROSE (EBUS arm) or with ROSE (ROSE arm). The primary end point was the rate of the successful accomplishment of the institution's clinical protocol for molecular profiling of nonsquamous non-small cell lung cancer (EGFR and KRAS testing, followed by ALK testing for tumors with EGFR and KRAS wild-type status). RESULTS: Complete genotyping was achieved in 108 of 126 patients (85.7%) (90.8% in the ROSE arm vs 80.3% in the EBUS arm, P = .09). The patients in the ROSE arm were less likely to have samples that could be used only for pathologic diagnosis because of minimal tumor burden (0 vs 6, P = .05), and were more likely to have the bronchoscopy terminated after a single biopsy site (58.9% vs 44.1%, P = .01). CONCLUSIONS: ROSE prevents the need for a repeat invasive diagnostic procedure aimed at molecular profiling in at least one out of 10 patients with advanced lung cancer and significantly reduces the risk of retrieving samples that can be used only for pathologic subtyping because of minimal tumor burden. Trisolini, Rocco; Cancellieri, Alessandra; Tinelli, Carmine; de Biase, Dario; Valentini, Ilaria; Casadei, Gianpiero; Paioli, Daniela; Ferrari, Franco; Gordini, Giovanni; Patelli, Marco; Tallini, Giovanni Trisolini, Rocco; Cancellieri, Alessandra; Tinelli, Carmine; de Biase, Dario; Valentini, Ilaria; Casadei, Gianpiero; Paioli, Daniela; Ferrari, Franco; Gordini, Giovanni; Patelli, Marco; Tallini, Giovanni

Purpose: 5-years overall survival (OS) in high grade conventional chondrosarcoma is about 50%. Grade has been identified as the main prognostic factor. Heterozigous isocitrate dehydrogenase (IDH) mutations are present in about half of conventional chondrosarcomas, with higher frequency in low grade lesions. IDH prognostic role is not fully understood. Aim of this study is to assess the frequency of IDH mutations in high grade chondrosarcoma, their relationship with clinical characteristics, and their prognostic role. Methods: patients who underwent surgery at Rizzoli between 2002 and 2012 with a diagnosis of G2- G3 conventional chondrosarcoma and fresh frozen tissue available were selected from archives. DNA extraction was performed with commercial kit. PCR amplification of exon 4 of IDH1 and IDH2 genes, and sequencing analysis with Sanger was performed. Results: 54 patients identified:18 (33%) were male, 36 (67%) female; median age was 62 (range 17-85 years). 40 (74%) patients had localized tumor, and 14 (26%) presented with metastases. Tumor was in the extremities in 25 (46%) patients. 41 (76%) of the cases were G2, 13 (24%) G3. 4 patients had a genetic predisposition (1 Maffucci syndrome and 3 Ollier disease). IDH mutation was detected in 26 (48%) of the patients (20 IDH1, 4 IDH2, and 2 patients both IDH1 and 2). Frequency of mutation was 17 (65%) in G2, and 9 (35%) in G3. 4/4 chondrosarcomas in with a syndrome presented a mutation. Gender, site and stage were not significantly different by mutational status. After a median follow-up of 124 months (range 1-166) the 5-year OS was 51% (95% CI:36-64), with no difference according to mutational status (5-year OS IDHmut 54% vs IDHwt 48%, p=0.45), and better survival for localized vs metastatic pts (68% vs 7%, p Citation Format: Elisabetta Setola, Stefania Benini, Alberto Righi, Gabriella Gamberi, Sofia Avnet, Elisa Carretta, Cristina Ferrari, Emanuela Palmerini, Pier Luigi Lollini, Marilena Cesari, Anna Paioli, Alessandra Longhi, Davide Maria Donati, Nicola Baldini. IDH mutations in G2-3 conventional chondrosarcoma of bone: a mono institutional experience [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5909.

e23564 Background: Activity of temozolomide (TEM) and irinotecan (IRI) in recurrent Ewing sarcoma (EWS) was demonstrated. Few data are available on TEMIRI use upfront. Biological predictive factors are lacking. Methods: This multi-institutional retrospective study (NCT03542097) included 59 patients with EWS. 8 patients with very high risk (HR) EWS (multivisceral ± bone marrow) received TEMIRI (TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1-5, every 21 days) upfront, 51 patients after relapse (28% in 1st line, 72% ≥ 2nd line). Overall response rate (ORR: CR+PR), SD, and PD, progression-free (PFS) and overall survival (OS) were assessed. The relationship between pre-treatment expression of MGMT and ABCG2 (when FFPE tissue available) with ORR, PFS and OS was evaluated. Results: Median age was 27 years (range 4-62 years): 47 patients (80%) were adults (≥18 years), 35 (61%) had ECOG 0 and 42 (71%) presented with multivisceral disease (+ bone marrow in 5). MGMT was positive in 16/30 (53%), ABCG2 in 4/33 (12%). ORR for upfront TEMIRI (n = 8) was 50% (CR + PR = 1 + 3), with SD 50%, while in recurrent EWS (n = 49, 2 patients no measurable by RECIST) ORR was 31% (CR + PR = 4 + 11), SD 38%, and PD 31%. A better ORR was observed in adult (p = 0.008) & ECOG 0 (p = 0.001) patients; MGMT & ABCG2 expression did not influence ORR. 6-mos PFS was 87% after TEMIRI upfront, 43% at recurrence (p = 0.06), and 65% vs 28% (p = 0.02) for ECOG 0 vs ECOG 1-2, respectively. 6-mos PFS was 62% in MGMT+ vs 33% in MGMT- (p = 0.4) and 75% in ABCG2+ vs 50% in ABCG2- (p = 0.7). Median time to progression (TTP) with upfront TEMIRI was 9 months (range 5-28 months), with 1 patient with ongoing CR at 56 months; median TTP at relapse was 3 months (1-29 months). MGMT and ABCG2 expression did not influence 1-yr OS, whereas ECOG (0 vs 1-2) did (88% vs 31% p < 0.001). Grade 3-4 diarrhea, neutropenia, and thrombocytopenia incidence was < 5%, 1 patient with recurrent kidney EWS died of acute liver failure. Conclusions: TEMIRI showed promising activity in a very unfavorable cohort of EWS patients, with manageable toxicity. Performance status correlated with 6-month PFS & OS whereas MGMT & ABCG2 did not. Clinical trial information: NCT03542097 .

Purpose: Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC. Methods: In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed. Patients underwent radiologic disease assessment every 3 months. Symptoms and adverse events were noted. Results: Nine patients were identified (6 male, 3 female), with a median age of 17 years (range 14–42 years). Primary sites were 6 spine–pelvis, 1 ulna, 1 tibia, and 1 humerus. Patients were followed for a median time of 23 months (range 3–55 months). Patients received a median of 8 denosumab administrations (range 3–61). All symptomatic patients had pain relief and 1 had paresthesia improvement. Signs of denosumab activity were observed after 3 to 6 months of administration: bone formation by computed tomography scan was demonstrated in all patients and magnetic resonance imaging gadolinium contrast media decrease was observed in 7/9 patients. Adverse events were negligible. At last follow-up, all patients were progression-free: 5 still on denosumab treatment, 2 off denosumab were disease-free 11 and 17 months after surgery, and the last 2 patients reported no progression 12 and 24 months after denosumab interruption and no surgery. Conclusions: Denosumab has substantial activity in ABCs, with favorable toxicity profile. We strongly support the use of surgery and/or embolization for the treatment of ABC, but denosumab could have a role as a therapeutic option in patients with uncontrollable, locally destructive, or recurrent disease.

Background: Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. Methods: Patients receiving TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1–5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed. Results: The median age of the 51 patients was 21 years (range 3–65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35–63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45–83] for ECOG 0, 34% [95% CI 14–54] for ECOG ≥1; p =.006) and LDH (6-mos PFS 62% [95% CI 44–79] for normal LDH, 22% [95% CI 3–42] for high LDH; p =.02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39–70), with RECIST response (p =.001) and ECOG (p =.0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%. Conclusions: This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.

Introduction and Objectives: Endosonography has become standard of care in the diagnostic work-up of mediastinal lymphadenopathy and peribronchial lung lesions, but its success rate in some specific settings/conditions may be hampered by limited needle flexibility and size. We report on our initial experience with the 19G Flex needle, characterized by larger size and greater flexibility as compared with the currently available cytology needles. Methods: Retrospective review of prospectively collected data on the first 13 consecutive patients submitted to endosonography with the 19G Flex needle. Patients were included if they had: a) suspicion of a histologically complex disease (i.e. lymphoma); b) suspicion of an advanced lung cancer possibly requiring extensive genotyping; c) a lesion whose sampling with a 22G needle had failed due to lack of visibility when the needle was loaded into the scope. Results: the 13 patients enrolled had a mean age of 58.15±17 years and a male to female ratio of 8:5. Target lesions (mean size 18.6±6.4 mm) were lymphadenopathies (9 patients), lung lesions (3 patients), and a pleural nodule (1 patient). Histology core/s and a definite diagnosis (adenocarcinoma, 4 cases; lymphoma, 2; mesothelioma, 2, metastases from extrathoracic tumors, 2; non-small-cell lung cancer not otherwise specifiable, 1; small cell carcinoma, 1; sarcoidosis, 1) were obtained in 100% of patients. A single case of self-resolving bleeding was the only complication we observed. Conclusions: Preliminary results obtained with the dedicated Flex 19G needle are promising, as sample size/quality is satisfactory and the needle influence on scope flexibility is minimal. This article is protected by copyright. All rights reserved.

Biogas is a chemical compound rich in methane, generated by the degradation of organic matter, flammable power and applicable to energy generation. Landfills are areas with great potential for biogas generation due to the large amount of organic matter contained in solid domestic waste. The sizing and design of projects to capture and generate energy in landfills depend on reliable estimates of future generation of biogas. The currently available models are deficient in many respects due to the exclusion of relevant factors in the biogas generation process. This paper presents the results of natural electric potential through geophysical logging technique, developed alongside gas drains located in areas with residues of different ages of landfill deposition, when accompanied by measures of biogas flow and rainfall, biweekly during 12 months. The key objective was to evaluate the sensitivity of the physical parameter to seasonal variations and its relation to the production of biogas. The results show that the availability of organic matter able to degradation was the main factor responsible for differences in biogas production between the drains examined, although there are variations in periods of drought or rain. The natural electric potential demonstrated proportional variations of biogas flow rates measured in drains with different ages, where the largest biogas flows are associated to more electronegative or more reducing areas

Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study. Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

A hemoglobina (Hb) e a hemeproteina das hemacias caracterizada pela ligacao reversivel ao O2 e, consequentemente, o transporte deste gas aos tecidos perifericos. Complementar aos estudos de funcao da Hb extraida de bolsas de sangue, este trabalho tem por objetivo a analise de parâmetros bioquimicos das bolsas de sangue (concentrado de hemacias, CH) apos processos de retirada de leucocitos (por filtracao, exposicao de irradiacao ? e processo misto de filtracao e irradiacao), com os intervalos de armazenamento de 48 horas, 21 dias e 42 dias. Resultados aqui apresentados parecem apontar para alteracoes bioquimicas da bolsa de sangue e modificacoes funcionais da Hb tanto em relacao ao tempo de armazenamento quanto pelos processos de leucorreducao.