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1.
Ann Oncol ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39241959

RESUMO

BACKGROUND: The administration of adjuvant imatinib during three years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. METHODS: IMADGIST (NCT02260505) was a multicenter open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-years arm) compared to Interruption (3-years arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to treat disease-free survival (DFS). Secondary endpoints include overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, safety. RESULTS: From December 24th 2014 to April 4th 2023; 136 patients aged ≥18, ECOG PS ≤2, with a localized GIST with a R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to NCCN risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-Years arm vs. 71 in the 6-Years arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients respectively. Respectively 52 (38%) and 71 (52%) of patients had a risk of relapse of 35-70% and >70%.. With a median follow-up of 55 (IQR=46-59) months post randomization, DFS was significantly superior in the 6-Years arm (HR: 0.40 [0.20-0.69], p=0.0008). Time to imatinib resistance, survival, adverse events and quality of life are not different in the 2 arms. CONCLUSIONS: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

2.
Ann Oncol ; 35(4): 351-363, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38246351

RESUMO

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Sarcoma/patologia , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologia , Biópsia , França/epidemiologia , Bases de Dados Factuais , Estudos Retrospectivos
3.
ScientificWorldJournal ; 2023: 8971590, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065772

RESUMO

Inspired by some open conjectures in a rational dynamical system by G. Ladas and Palladino, in this paper, we consider the problem of solving a third-order difference equation. We comment the conjecture by Ladas. A third-order rational difference equation is solved analytically. The solution is compared with the solution to the linearized equation. We show that the solution to the linearized equation is not good, in general. The methods employed here may be used to solve other rational difference equations. The period of the solution is calculated. We illustrate the accuracy of the obtained solutions in concrete examples.

4.
ScientificWorldJournal ; 2022: 3131253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35177958

RESUMO

The Duffing oscillator of a system with strong quadratic damping is considered. We give an elementary approximate analytical solution to this oscillator in terms of exponential and trigonometric functions. We compare the analytical approximant with the Runge-Kutta numerical solution. We also solve the oscillator by menas of He's homotopy method and the famous Krylov-Bogoliubov-Mitropolsky method. The approximant allows estimating the points at which the solution crosses the horizontal axis.

5.
ScientificWorldJournal ; 2022: 2711466, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479552

RESUMO

Future scientific and technological evolution in many areas of applied mathematics and modern physics will necessarily depend on dealing with complex systems. Such systems are complex in both their composition and behavior, namely, dealing with complex dynamical systems using different types of Duffing equations, such as real Duffing equations and complex Duffing equations. In this paper, we derive an analytical solution to a complex Duffing equation. We extend the Krýlov-Bogoliúbov-Mitropólsky method for solving a coupled system of nonlinear oscillators and apply it to solve a generalized form of a complex Duffing equation.

6.
ScientificWorldJournal ; 2022: 4808065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341161

RESUMO

In this paper, we obtain the approximate value of 42.9815 arcsec/century for Mercury's perihelion precession by solving both numerically and analytically the nonlinear ordinary differential equation derived from the geodesic equation in Einstein's Theory of Relativity. We also compare our result with known results, and we illustrate graphically the way Mercury's perihelion moves. The results we obtained are applicable to any body that moves around the Sun. We give predictions about the value of the Cosmological Constant. Simple algebraic formulas allow to estimate perihelion shifts with high accuracy.

7.
Clin Infect Dis ; 73(4): e913-e920, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398953

RESUMO

BACKGROUND: Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. METHODS: Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014-June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into 1 episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting-specific incidence estimates were calculated using age-stratified bootstrapping. RESULTS: The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged < 5 years (20.4 episodes per 1000 PY), followed by adults aged ≥ 65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY; astrovirus: 1.3 per 1000 PY; rotavirus: 0.5 per 1000 PY). CONCLUSIONS: Viral enteropathogens, particularly norovirus, are important contributors to MAAGE, especially among children < 5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Infecções por Rotavirus , Rotavirus , Sapovirus , Adulto , Infecções por Caliciviridae/epidemiologia , Criança , Fezes , Gastroenterite/epidemiologia , Humanos , Lactente , Estados Unidos/epidemiologia
8.
Ann Oncol ; 32(8): 1034-1044, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33932507

RESUMO

BACKGROUND: The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m2 every 3 weeks or BSC, stratified into L-STS (liposarcoma/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from the BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. RESULTS: Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. CONCLUSION: Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.


Assuntos
Sarcoma , Tetra-Hidroisoquinolinas , Adulto , Antineoplásicos Alquilantes/efeitos adversos , Dioxóis/efeitos adversos , Intervalo Livre de Doença , Humanos , Qualidade de Vida , Sarcoma/tratamento farmacológico , Tetra-Hidroisoquinolinas/efeitos adversos , Trabectedina
9.
MMWR Morb Mortal Wkly Rep ; 70(46): 1608-1612, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34793417

RESUMO

Population-based rates of infection with SARS-CoV-2 (the virus that causes COVID-19) and related health care utilization help determine estimates of COVID-19 vaccine effectiveness and averted illnesses, especially since the SARS-CoV-2 B.1.617.2 (Delta) variant began circulating in June 2021. Among members aged ≥12 years of a large integrated health care delivery system in Oregon and Washington, incidence of laboratory-confirmed SARS-CoV-2 infection, emergency department (ED) visits, and hospitalizations were calculated by COVID-19 vaccination status, vaccine product, age, race, and ethnicity. Infection after full vaccination was defined as a positive SARS-CoV-2 molecular test result ≥14 days after completion of an authorized COVID-19 vaccination series.* During the July-September 2021 surveillance period, SARS-CoV-2 infection occurred among 4,146 of 137,616 unvaccinated persons (30.1 per 1,000 persons) and 3,009 of 344,848 fully vaccinated persons (8.7 per 1,000). Incidence was higher among unvaccinated persons than among vaccinated persons across all demographic strata. Unvaccinated persons with SARS-CoV-2 infection were more than twice as likely to receive ED care (18.5%) or to be hospitalized (9.0%) than were vaccinated persons with COVID-19 (8.1% and 3.9%, respectively). The crude mortality rate was also higher among unvaccinated patients (0.43 per 1,000) than in fully vaccinated patients (0.06 per 1,000). These data support CDC recommendations for COVID-19 vaccination, including additional and booster doses, to protect individual persons and communities against COVID-19, including illness and hospitalization caused by the Delta variant (1).


Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Oregon/epidemiologia , Vacinação/estatística & dados numéricos , Washington/epidemiologia , Adulto Jovem
10.
Int J Gynecol Cancer ; 29(4): 691-698, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30772825

RESUMO

OBJECTIVE: High grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear. METHODS: A retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I-III) treated in 10 French Sarcoma Group centers was conducted. RESULTS: 39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6-112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3-49.1) and 23 (4.4-41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I-II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival. CONCLUSIONS: The standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Gradação de Tumores , Ovariectomia , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-28833787

RESUMO

This study investigated the efficacy of post-treatment hydrotherapy as supportive care for management of persistent/long-lasting dermatologic adverse events (dAEs) induced in breast cancer survivors by adjuvant therapy, and its impact on quality of life (QoL). Patients in complete remission after standardised (neo)adjuvant chemotherapy, surgery and radiotherapy combination treatment for infiltrating HR+/HER2-breast carcinoma were enrolled in this randomised, multicentre controlled study 1-5 weeks after completing radiotherapy. The control group (CG, n = 33) received best supportive care and the treatment group (HG, n = 35) received 3-weeks of specific hydrotherapy. The primary criterion was change in QoL (QLQ-BR23) after hydrotherapy. Clinical grading of dAEs, cancer-related QoL (QLQ-C30), dermatologic QoL (DLQI) and general psychological well-being (PGWBI) were assessed. Significant dAEs were found at inclusion in both groups (n = 261). Most items showed significantly greater improvement in the HG versus CG group: QLQ-BR23 (breast [p = .0001] and arm symptoms [p = .0015], systemic therapy side effects [p = .0044], body image [p = .0139]), some dAE grading, DLQI (p = .0002) and PGWBI (p = .0028). Xerosis (88% of patients at inclusion) completely healed in all HG patients. Specific hydrotherapy is an effective supportive care for highly prevalent and long-lasting dAEs occurring after early breast cancer treatment, including chemotherapy, and leads to improved QoL and dermatologic toxicities.


Assuntos
Neoplasias da Mama/terapia , Carcinoma/terapia , Quimioterapia Adjuvante/efeitos adversos , Hidroterapia/métodos , Mastectomia , Radioterapia Adjuvante/efeitos adversos , Higiene da Pele/métodos , Dermatopatias/terapia , Adulto , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Ciclofosfamida/efeitos adversos , Docetaxel , Emolientes/uso terapêutico , Epirubicina/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Hormônio Liberador de Gonadotropina/agonistas , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/terapia , Humanos , Hiperpigmentação/etiologia , Hiperpigmentação/terapia , Linfedema/etiologia , Linfedema/terapia , Drenagem Linfática Manual/métodos , Massagem/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Prurido/etiologia , Prurido/terapia , Qualidade de Vida , Radiodermite/etiologia , Radiodermite/terapia , Dermatopatias/etiologia , Tamoxifeno/uso terapêutico , Taxoides/efeitos adversos
12.
Ann Oncol ; 28(8): 1979-1987, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28838212

RESUMO

BACKGROUND: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. PATIENTS AND METHODS: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. RESULTS: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. CONCLUSION: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Tumores Fibrosos Solitários/epidemiologia , Tumores Fibrosos Solitários/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , França , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Análise de Sobrevida
13.
Br J Surg ; 104(4): 347-357, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28199014

RESUMO

BACKGROUND: Extra-abdominal desmoid-type fibromatosis (DF) is a rare, locally aggressive neoplasm that is usually managed conservatively. When treatment is indicated, it typically involves surgical resection, possibly with adjuvant radiotherapy. The indications for postoperative radiotherapy and its effectiveness are unclear. The objective of this study was to estimate the effect of surgical resection margins and adjuvant radiotherapy on rates of recurrence of DF. METHODS: Literature published between 1999 and 2015 was extracted from MEDLINE, Embase, Cochrane Central Registry of Trials, Web of Science and Google Scholar. Recurrence rate was analysed by meta-analysis and compared between subgroups. RESULTS: Sixteen reports were included, consisting of a total of 1295 patients with DF. In patients treated by surgical resection alone, the risk of local recurrence was almost twofold higher for those with microscopically positive resection margins (risk ratio (RR) 1·78, 95 per cent c.i. 1·40 to 2·26). Adjuvant radiotherapy after surgery with negative margins had no detectable benefit on recurrence. In contrast, after incomplete surgical resection, adjuvant radiotherapy improved recurrence rates both in patients with primary tumours (RR 1·54, 1·05 to 2·27) and in those with recurrent DF (RR 1·60, 1·12 to 2·28). CONCLUSION: DF resected with microscopically positive margins has a higher risk of recurrence. Adjuvant radiotherapy appears to reduce the risk of recurrence after incomplete surgical resection, particularly in patients with recurrent tumours.


Assuntos
Fibromatose Abdominal/cirurgia , Fibromatose Abdominal/radioterapia , Humanos , Margens de Excisão , Recidiva Local de Neoplasia/etiologia , Radioterapia Adjuvante , Fatores de Risco , Resultado do Tratamento
14.
Reprod Biol Endocrinol ; 15(1): 52, 2017 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-28716123

RESUMO

BACKGROUND: Modeling early endometrial differentiation is a crucial step towards understanding the divergent pathways between normal and ectopic endometrial development as seen in endometriosis. METHODS: To investigate these pathways, mouse embryonic stem cells (mESCs) and embryoid bodies (EBs) were differentiated in standard EB medium (EBM). Immunofluorescence (IF) staining and reverse-transcription polymerase chain reaction (RT-PCR) were used to detect expression of human endometrial cell markers on differentiating cells, which were sorted into distinct populations using fluorescence-activated cell sorting (FACS). RESULTS: A subpopulation (50%) of early differentiating mESCs expressed both glandular (CD9) and stromal (CD13) markers of human endometrium, suggestive of a novel endometrial precursor cell population. We further isolated a small population of endometrial mesenchymal stem cells, CD45-/CD146+/PDGFR-ß+, from differentiating EBs, representing 0.7% of total cells. Finally, quantitative PCR demonstrated significantly amplified expression of transcription factors Hoxa10 and Foxa2 in CD13+ EBs isolated by FACS (p = 0.03). CONCLUSIONS: These findings demonstrate that mESCs have the capacity to express human endometrial cell markers and demonstrate potential differentiation pathways of endometrial precursor and mesenchymal stem cells, providing an in vitro system to model early endometrial tissue development. This model represents a key step in elucidating the mechanisms of ectopic endometrial tissue growth. Such a system could enable the development of strategies to prevent endometriosis and identify approaches for non-invasive monitoring of disease progression.


Assuntos
Biomarcadores/metabolismo , Diferenciação Celular , Endométrio/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Animais , Antígenos CD13/genética , Antígenos CD13/metabolismo , Antígeno CD146/genética , Antígeno CD146/metabolismo , Linhagem Celular , Corpos Embrioides/metabolismo , Endometriose/diagnóstico , Endometriose/genética , Endometriose/metabolismo , Feminino , Expressão Gênica , Humanos , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Células-Tronco Embrionárias Murinas/citologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Tetraspanina 29/genética , Tetraspanina 29/metabolismo
16.
BMC Public Health ; 16: 566, 2016 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-27411474

RESUMO

BACKGROUND: Many health departments collaborate with community organizations on community health improvement processes. While a number of resources exist to plan and implement a community health improvement plan (CHIP), little empirical evidence exists on how to leverage and expand partnerships when implementing a CHIP. The purpose of this study was to identify characteristics of the network involved in implementing the CHIP in one large community. The aims of this analysis are to: 1) identify essential network partners (and thereby highlight potential network gaps), 2) gauge current levels of partner involvement, 3) understand and effectively leverage network resources, and 4) enable a data-driven approach for future collaborative network improvements. METHODS: We collected primary data via survey from n = 41 organizations involved in the Health Improvement Partnership of Maricopa County (HIPMC), in Arizona. Using the previously validated Program to Analyze, Record, and Track Networks to Enhance Relationships (PARTNER) tool, organizations provided information on existing ties with other coalition members, including frequency and depth of partnership and eight categories of perceived value/trust of each current partner organization. RESULTS: The coalition's overall network had a density score of 30 %, degree centralization score of 73 %, and trust score of 81 %. Network maps are presented to identify existing relationships between HIPMC members according to partnership frequency and intensity, duration of involvement in the coalition, and self-reported contributions to the coalition. Overall, number of ties and other partnership measures were positively correlated with an organization's perceived value and trustworthiness as rated by other coalition members. CONCLUSIONS: Our study presents a novel use of social network analysis methods to evaluate the coalition of organizations involved in implementing a CHIP in an urban community. The large coalition had relatively low network density but high degree centralization-meaning key organizations link organizations otherwise not tightly partnering. Coalition members rated each other highly on trust, a positive sign for future partnership development efforts. Examination of network maps reveal key organizations that can be targeted for future partnership facilitation and expansion. Future network data collection will enable exploration of longitudinal trends and exploration of network characteristics versus health behavior, status, and outcome changes.


Assuntos
Planejamento em Saúde Comunitária/organização & administração , Serviços de Saúde Comunitária/organização & administração , Comportamento Cooperativo , Implementação de Plano de Saúde/métodos , Apoio Social , Arizona , Humanos , Inquéritos e Questionários
17.
Br J Cancer ; 112(4): 688-92, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25602962

RESUMO

BACKGROUND: This study aimed to determine whether the BRCA1 haplotype was associated with trabectedin efficacy in soft-tissue sarcoma (STS) patients. METHODS: We analysed BRCA1 single-nucleotide polymorphisms (SNPs) in tumour specimens from 135 advanced STS patients enrolled in published phase 2 trials or in a compassionate-use programme of trabectedin. Forty-four advanced STS patients treated with doxorubicin and 85 patients with localised STS served as controls. The 6-month nonprogression rate and overall survival (OS) were analysed according to BRCA1 haplotype using log-rank tests. RESULTS: A favourable BRCA1 haplotype (presence of at least one AAAG allele) was significantly associated with an improved 6-month nonprogression rate. It was the only variable significantly associated with OS. No correlations were found between outcomes for patients with localised or advanced STS treated with doxorubicin. CONCLUSIONS: The BRCA1 haplotype represents a potential DNA repair biomarker that can be used for the prediction of response to trabectedin in STS patients.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Proteína BRCA1/genética , Dioxóis/uso terapêutico , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/genética , Tetra-Hidroisoquinolinas/uso terapêutico , Adolescente , Adulto , Idoso , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios de Uso Compassivo/estatística & dados numéricos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Trabectedina , Resultado do Tratamento , Adulto Jovem
18.
Ann Oncol ; 26(10): 2168-73, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26202596

RESUMO

BACKGROUND: There is no consensual treatment of locally advanced or metastatic chordomas. PATIENTS AND METHODS: We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. RESULTS: Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30-86) years. There were 17 men and 10 women. Twelve patients had been previously treated with chemotherapy and molecularly targeted agents. The maximum toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27 [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free rate of 73.0% (95% CI 46.1-88.0) and a 12-month overall survival rate of 86.5% (95% CI 55.8-96.5). Survival curves were similar in pretreated and not pretreated patients. DISCUSSION: Additional clinical trials further exploring sorafenib as a treatment of locally advanced or metastatic chordomas are warranted.


Assuntos
Antineoplásicos/uso terapêutico , Cordoma/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cordoma/mortalidade , Cordoma/secundário , Feminino , Seguimentos , França , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/uso terapêutico , Prognóstico , Sarcoma/mortalidade , Sarcoma/patologia , Sorafenibe , Taxa de Sobrevida
19.
Pediatr Surg Int ; 30(8): 797-802, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25023942

RESUMO

PURPOSE: A number of patients operated on for Hirschsprung disease continue to have constipation and abdominal distension for years after surgery. Some authors have proposed that ischemia during surgery may induce secondary aganglionosis. The aim of the present study was to study the effects of ischemia on the enteric nervous system of sigmoid colon in an animal model. METHODS: A surgical model of colonic ischemia was created. 34 adult Sprague-Dawley rats underwent a laparotomy where the marginal arterioles of the sigmoid colon were ligated. After that, a section in the middle segment of the sigmoid colon was performed followed by an anastomosis. The presence of ischemia was assessed by measurement of visible light spectroscopy tissue oximetry and histological examination. Colonic function was assessed by evaluation of stool weight. Rats were killed at 1, 8 and 12 weeks after the operation. 12 rats were sham-operated. Enteric nervous system was evaluated by means of immunohistochemistry with NGFR p75. Quantitative analysis of the number of ganglia and ganglion cells in the myenteric plexus was performed. RESULTS: The surgical model of colonic ischemia significantly decreased tissue oxygenation (pre-surgical = 54.69 ± 7.32 %; post-surgical = 27.37 ± 9.2 %; p < 0.001). There was no disturbance in body-weight gaining in experimental groups and daily stool output did not vary after surgery (pre-surgical = 4.24 ± 0.94 g; post-surgical = 3.82 ± 1 g; p = 0.09). All experimental groups showed persistent ganglia. However, there was a significant decrease in the number of ganglia in all the experimental groups compared to control (1w: 45.91 ± 7.66; 8w: 44.17 ± 10.56; 12w: 36.17 ± 15.06 vs control: 56.88 ± 8.66; p < 0.01). The number of total ganglion cells was significantly reduced only in the experimental group killed at week 12 compared to control (1w: 539 ± 167.58; 8w: 488.58 ± 154.41; 12w: 343.94 ± 161.91 vs control: 513.96 ± 126.97; p < 0.01). The rate of ganglion cells per ganglia was significantly higher in the groups killed at week 1 and 8 versus control group (1w: 11.63 ± 2.53; 8w: 11.11 ± 2.56; 12w: 9.34 ± 1.16 vs control: 9.02 ± 1.81; p < 0.05). CONCLUSION: Long-term follow-up after surgically induced colonic ischemia in the rat showed a decreased number of ganglion cells and ganglia. Nevertheless, it did not produce aganglionosis.


Assuntos
Colo Sigmoide/irrigação sanguínea , Doença de Hirschsprung/cirurgia , Complicações Intraoperatórias/prevenção & controle , Isquemia/prevenção & controle , Animais , Colo Sigmoide/patologia , Modelos Animais de Doenças , Sistema Nervoso Entérico/patologia , Sistema Nervoso Entérico/fisiologia , Doença de Hirschsprung/patologia , Mucosa Intestinal/patologia , Isquemia/patologia , Ratos , Ratos Sprague-Dawley
20.
Am J Trop Med Hyg ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137750

RESUMO

Neurocysticercosis is a parasitic disease of major public health importance. Definitive diagnosis requires neuroimaging, which is typically unavailable in rural impoverished regions of endemicity. Screening immunoassays can support diagnosis in this setting by identifying individuals most likely to have severe forms of disease for referral to imaging. Urine sampling is convenient, painless, and generally well accepted. We developed a rapid point-of-care (POC) assay to detect urinary antigens and assessed concordance with a standard antigen ELISA (Ag-ELISA), both using monoclonal antibodies TsW8/TsW5. From 28,145 stored community samples with Ag-ELISA results, we selected 843 for comparison, 281 each from nonreactive (ratio <1), reactive-below-cutoff (ratio 1:3), and positive (ratio ≥3) samples. Overall agreement was 73.6%, with strong agreement observed in the nonreactive (280/281, 99.6%) and positive (255/281, 90.8%) groups. This affordable noninvasive POC test can be applied to identify individuals in the community most at risk of developing severe disease.

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