Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 144
Filtrar
1.
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
2.
Radiother Oncol ; 190: 109984, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926332

RESUMO

BACKGROUND & AIM: Irradiation of the salivary glands during head and neck cancer treatment induces cellular senescence in response to DNA damage and contributes to radiation-induced hyposalivation by affecting the salivary gland stem/progenitor cell (SGSC) niche. Cellular senescence, such as that induced by radiation, is a state of cell-cycle arrest, accompanied by an altered pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP) with potential detrimental effects on the surrounding microenvironment. We hypothesized that the pro-regenerative properties of mesenchymal stem cells (MSCs) may attenuate cellular senescence post-irradiation. Therefore, here we evaluated the effects of adipose-derived MSCs (ADSCs) on the radiation-induced response of salivary gland organoids (SGOs). METHODS: Proteomic analyses to identify soluble mediators released by ADSCs co-cultured with SGOS revealed secretion of hepatocyte growth factor (HGF) in ADSCs, suggesting a possible role in the stem cell crosstalk. Next, the effect of recombinant HGF in the culture media of ex vivo grown salivary gland cells was tested in 2D monolayers and 3D organoid models. RESULTS: Treatment with HGF robustly increased salivary gland cell proliferation. Importantly, HGF supplementation post-irradiation enhanced proliferation at lower doses of radiation (0, 3, 7 Gy), but not at higher doses (10, 14 Gy) where most cells stained positive for senescence-associated beta-galactosidase. Furthermore, HGF had no effect on the senescence-associated secretory phenotype (SASP) of irradiated SGOs, suggesting there may be compensatory proliferation by cell-division competent cells instead of a reversal of cellular senescence after irradiation. CONCLUSION: ADSCs may positively influence radiation recovery through HGF secretion and can promote the ex vivo expansion of salivary gland stem/progenitor cells to enhance the effects of co-transplanted SGSC.


Assuntos
Fator de Crescimento de Hepatócito , Células-Tronco Mesenquimais , Humanos , Fator de Crescimento de Hepatócito/farmacologia , Proteômica , Glândulas Salivares , Senescência Celular/efeitos da radiação , Proliferação de Células
3.
PLoS One ; 18(10): e0293739, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37906587

RESUMO

BACKGROUND: In the United States, public health surveillance systems often underestimate the burden of acute gastroenteritis (AGE) because they only identify disease among those who interact with the healthcare system. OBJECTIVE: To identify factors associated with healthcare-seeking behavior among individuals experiencing community-acquired AGE. METHODS: From October 2016 -September 2017, we conducted a weekly, age-stratified, random sample of Kaiser Permanente Northwest members located in northwest Oregon and southwest Washington, United States. Individuals who completed the online survey and experienced AGE were included in the analysis. Univariate and multivariable logistic regressions were performed to identify predictors of healthcare-seeking behavior. RESULTS: Of the 3,894 survey respondents, 395 experienced an AGE episode and were eligible for analysis, of whom, 82 (21%) sought care for their AGE episode. In the final multivariable model, individuals with a concurrent fever (odds ratio [OR]: 4.76, 95% confidence interval [95% CI]: 2.48-9.13), increased diarrhea duration (≥6 days vs 1-4 days, OR: 4.22, 95% CI: 1.78-10.03), or increased vomiting duration (≥3 days vs 1 days, OR: 2.97, 95% CI: 1.22-7.26), were significantly more likely to seek healthcare. In the adjusted model, no sociodemographic or chronic disease variables were associated with healthcare-seeking behavior. CONCLUSION: These findings suggest that individuals with a short duration of AGE and those without concurrent fever are underrepresented in healthcare facility-based surveillance systems.


Assuntos
Gastroenterite , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Estados Unidos/epidemiologia , Diarreia/epidemiologia , Atenção à Saúde , Gastroenterite/epidemiologia , Gastroenterite/terapia , Oregon/epidemiologia , Febre/epidemiologia
4.
Open Forum Infect Dis ; 10(7): ofad287, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37426945

RESUMO

Background: Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multidrug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision making. Methods: We evaluated UPEC resistance over time by care setting (in-person vs virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021. Results: We included 174 185 individuals who had ≥1 UPEC uUTI (233 974 isolates) (92% female, 46% Hispanic, mean age 52 years [standard deviation 20]). Overall, prevalence of UPEC MDR decreased during the study period (13% to 12%) both in virtual and in-person settings (P for trend <.001). Resistance to penicillins overall (29%), coresistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving the 2 plus ≥1 antibiotic class were common (10%). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time and by care setting. Conclusions: We observed a slight decrease in both class-specific antimicrobial resistance and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX. Resistance patterns were consistent over time and similar in both in-person and virtual settings. Virtual healthcare may expand access to UTI care.

5.
JMIR Res Protoc ; 12: e45109, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37145842

RESUMO

BACKGROUND: Overuse of antibiotics contributes to antimicrobial resistance (AMR) and is a growing threat to human health worldwide. Previous work suggests a link between antimicrobial use in poultry and human AMR extraintestinal pathogenic Escherichia coli (E coli) urinary tract infections (UTIs). However, few US-based studies exist, and none have comprehensively assessed both foodborne and environmental pathways using advanced molecular and spatial epidemiologic methods in a quasi-experimental design. Recently, California enacted Senate Bill 27 (SB27), which changed previous policy to require a veterinarian's prescription for the use of antibiotic drugs, and which banned antibiotic use for disease prevention in livestock. This provided an opportunity to evaluate whether SB27 will result in a reduction in antimicrobial-resistant infections in humans. OBJECTIVE: We describe in detail the methods implemented to achieve the overarching objective of this study to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTIs. METHODS: A summary of the overall approach and the partnerships between Columbia University, George Washington University (GWU), Johns Hopkins Bloomberg School of Public Health, Kaiser Permanente Southern California (KPSC) Research and Evaluation, the Natural Resources Defense Council, Sanger Institute at Stanford University, Sutter Health Center for Health Systems Research, the University of Cambridge, and the University of Oxford is presented. The collection, quality control testing, and shipment of retail meat and clinical samples are described. Retail meat (chicken, beef, turkey, and pork) was purchased from stores throughout Southern California from 2017 to 2021. After processing at KPSC, it was shipped to GWU for testing. From 2016 to 2021, after clinical specimens were processed for routine clinical purposes and immediately before discarding, those with isolated colonies of E coli, Campylobacter, and Salmonella from KPSC members were collected and processed to be shipped for testing at GWU. Detailed methods of the isolation and testing as well as the whole-genome sequencing of the meat and clinical samples at GWU are described. KPSC electronic health record data were used to track UTI cases and AMR patterns among the cultured specimens. Similarly, Sutter Health electronic health record data were used to track UTI cases in its Northern California patient population. RESULTS: From 2017 to 2021, overall, 12,616 retail meat samples were purchased from 472 unique stores across Southern California. In addition, 31,643 positive clinical cultures were collected from KPSC members during the same study period. CONCLUSIONS: Here, we presented data collection methods for the study, which was conducted to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTI. To date, it is one of the largest studies of its kind to be conducted. The data collected during this study will be used as the foundation for future analyses specific to the various objectives of this large body of work. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45109.

6.
Perm J ; 27(2): 75-86, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37154719

RESUMO

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.


Assuntos
Síndromes da Dor Regional Complexa , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Criança , Humanos , Adulto Jovem , Síndromes da Dor Regional Complexa/epidemiologia , Síndromes da Dor Regional Complexa/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Estudos Retrospectivos , Extremidade Superior , Vacinação
7.
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.

8.
Int J Biol Macromol ; 235: 123796, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36822293

RESUMO

New imaging agents are required in cancer diagnosis to enhance the diagnostic accuracy, classification, and therapeutic management of tumors. Nanomaterials have emerged as a promising alternative to developing new nanostructures with imaging applications. In this study, a heterostructure based on barium titanate (BT), zinc oxide (ZnO), and erbium (Er) was prepared and coated with Chitosan (CS) to investigate their stability and compatibility with biological systems. The structure, particle morphology, luminescence properties, stability, and cytotoxicity of different nanoparticles (NPs) were assessed. The results demonstrated the formation of a [BT@ZnO:Er]-CS heterostructure, which is consistent with the relative intensities and positions of peaks in the X-ray diffraction (XRD) with an average crystallite size of ~76 nm. The electrokinetic measurement results indicate that the coated NPs are the most stable and have an average size close to 200 nm when the pH is between 3 and 5. Finally, we presented a cytotoxicity study of naked and CS-coated NPs. The results indicate that naked NPs exhibit varying cellular toxicity, as indicated by decreased cell viability, morphological changes, and an increase in an apoptotic marker. The CS-coated NPs prevented the cytotoxic effect of the naked NPs, demonstrating the significance of CS as a stabilizing agent.


Assuntos
Quitosana , Óxido de Zinco , Óxido de Zinco/química , Quitosana/farmacologia , Quitosana/química , Érbio , Antibacterianos/química , Testes de Sensibilidade Microbiana
9.
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.

10.
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.

11.
J Pediatric Infect Dis Soc ; 11(12): 586-589, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36070595

RESUMO

We assessed rotavirus vaccine impact using data on acute gastroenteritis (AGE) encounters within an integrated healthcare delivery system during 2000-2018. Following rotavirus vaccine introduction, all-cause AGE rates among children <5 years declined by 36% (95% confidence interval [CI]: 32%-40%) for outpatient and 54% (95% CI: 46%-60%) for inpatient encounters.


Assuntos
Prestação Integrada de Cuidados de Saúde , Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Criança , Humanos , Estados Unidos/epidemiologia , Lactente , Pré-Escolar , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Hospitalização , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle
12.
ESMO Open ; 7(5): 100578, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36116422

RESUMO

BACKGROUND: The role of both hormonal contraception and pregnancy on the outcomes of desmoid-type fibromatosis (DF) is debatable. MATERIALS AND METHODS: In the present study, we selected female patients of childbearing age from the prospective ALTITUDES cohort. The primary study endpoint was event-free survival (EFS), with an event defined as relapse or progression. We estimated the risk of events according to the use of hormonal contraception [estrogen-progestin (EP) and progestin] and pregnancy status using multivariate time-dependent models, controlling for major confounders. RESULTS: A total of 242 patients (median age, 34.7 years) were included in the present study. The abdominal wall was the most common tumor site (51%). Patients were managed by active surveillance (80%) or surgery (20%). Pregnancy occurred within 24 months before, at the time of, and after DF diagnosis in 33%, 5%, and 10% of the cases, respectively. Exposure to hormonal contraception was documented within 24 months before, at the time of, and after diagnosis in 44%, 34%, and 39% of the cases, respectively. The 2-year EFS was 75%. After adjusting for DF location, tumor size, front-line treatment strategy, and hormonal contraception, we observed an increased risk of events occurring at 24 months after pregnancy [hazard ratio (HR) = 2.09, P = 0.018]. We observed no statistically significant association between the risk of events and current EP exposure (HR = 1.28, P = 0.65), recent EP exposure (within 1-24 months, HR = 1.38, P = 0.39), current progestin exposure (HR = 0.81, P = 0.66), or recent progestin exposure (HR = 1.05, P = 0.91). CONCLUSIONS: In our study, a recent history of pregnancy was associated with an increased risk of progression/relapse in patients with newly diagnosed DF, whereas hormonal contraception did not demonstrate an association with progression/relapse.


Assuntos
Anticoncepcionais , Fibromatose Agressiva , Humanos , Gravidez , Feminino , Adulto , Progestinas/efeitos adversos , Fibromatose Agressiva/induzido quimicamente , Estudos Prospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/induzido quimicamente , Estrogênios
13.
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.

14.
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
15.
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
16.
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
18.
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
19.
Food Chem Toxicol ; 124: 411-422, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30576709

RESUMO

Dyssodia tagetiflora is known as 'Tzaracata' and 'flor de muerto'. Recently, D. tagetiflora has been reported to have antioxidant activities in its polar extracts as well as insecticidal activities. Hyperoside (1), avicularin (2) and avicularin acetate (3) have been isolated previously. However, the temporary variation in glycoside flavonoids biosynthesis, as well as antibacterial and chemoprotective activities, have not been reported. The amount of 1, 2 and 3 in the different collections was characterized by HPLC-MS. Two new C-glycosides were characterized, quercetin-4'-methyl ether 6-C glucoside (A1) and quercetin-4'-methyl ether 8-C glucoside (A2), as well as [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]3,4,5-trihydroxyoxane-2,6-dicarboxylate (A3). This is the first report of the presence of C-C flavonoid glycosides compounds in the genus Dyssodia. Hyperoside was the majority compound at all collections. The methanolic extracts of August 2016 and October 2017 were active against Micrococcus luteus and Bacillus subtillis. The methanolic extract has chemoprotective effects because, when applied topically in SKH-1 mice, it decreases the severity of epidermal damage induced by acute exposure to ultraviolet radiation. In addition, cutaneous photocarcinogenesis was decreased in mice treated with the extract. The methanolic extract of D. tagetiflora has chemoprotective properties by decreasing the damage caused by acute and chronic exposure to UV in mice.


Assuntos
Antibacterianos/farmacologia , Asteraceae/química , Flavonóis/farmacologia , Glicosídeos/farmacologia , Extratos Vegetais/farmacologia , Protetores contra Radiação/farmacologia , Animais , Antibacterianos/isolamento & purificação , Asteraceae/metabolismo , Bacillus subtilis/efeitos dos fármacos , Eritema/prevenção & controle , Feminino , Flavonóis/isolamento & purificação , Glicosídeos/isolamento & purificação , Inflamação/prevenção & controle , Camundongos , Micrococcus luteus/efeitos dos fármacos , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/isolamento & purificação , Protetores contra Radiação/isolamento & purificação , Pele/patologia , Pele/efeitos da radiação , Fatores de Tempo , Raios Ultravioleta
20.
PLoS One ; 13(8): e0201805, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30075030

RESUMO

BACKGROUND: This study presents a novel methodology for estimating all-age, population-based incidence rates of norovirus and other pathogens that contribute to acute gastroenteritis in the United States using an integrated healthcare delivery system as a surveillance platform. METHODS: All cases of medically attended acute gastroenteritis within the delivery system were identified from April 1, 2014 through September 30, 2016. A sample of these eligible patients were selected to participate in two phone-based surveys and to self-collect a stool sample for laboratory testing. To ascertain household transmission patterns, information on household members with acute gastroenteritis was gathered from participants, and symptomatic household members were contacted to participate in a survey and provide stool sample as well. RESULTS: 54% of individuals who met enrollment criteria agreed to participate, and 76% of those individuals returned a stool sample. Among household members, 85% of eligible individuals agreed to participate, and 68% of those returned a stool sample. Participant demographics were similar to those of the eligible population, although minority racial/ethnic groups were somewhat underrepresented in the final sample. CONCLUSIONS: This study demonstrates the feasibility of conducting acute infectious disease research within an integrated health care delivery system. The surveillance, sampling, recruitment, and data collection methods described here are broadly applicable to conduct baseline and epidemiological assessments, as well as for other research requiring representative samples of stool specimens.


Assuntos
Prestação Integrada de Cuidados de Saúde , Monitoramento Epidemiológico , Gastroenterite/epidemiologia , Gastroenterite/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Prestação Integrada de Cuidados de Saúde/métodos , Estudos de Viabilidade , Fezes/microbiologia , Fezes/virologia , Feminino , Seguimentos , Gastroenterite/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...