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1.
J Acoust Soc Am ; 153(4): 2469, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37092951

RESUMO

Passive acoustic monitoring (PAM) offers considerable potential for density estimation of cryptic cetaceans, such as beaked whales. However, comparative studies on the accuracy of PAM density estimates from these species are lacking. Concurrent, low-cost drifting PAM, with SoundTraps suspended at 200 m depth, and land-based sightings, were conducted off the Canary Islands. Beaked whale density was estimated using a cue-count method, with click production rate and the probability of click detection derived from digital acoustic recording tags (DTags), and distance sampling techniques, adapted to fixed-point visual surveys. Of 32 870 detections obtained throughout 206 h of PAM recordings, 68% were classified as "certain" beaked whale clicks. Acoustic detection probability was 0.15 [coefficient variation (CV) 0.24] and click production rate was 0.46 clicks s - 1 (CV 0.05). PAM density estimates were in the range of 21.5 or 48.6 whales per 1000 km2 [CV 0.50 or 0.44, 95% confidence interval (CI) 20.7-22.4 or 47-50.9), depending on whether "uncertain" clicks were considered. Density estimates from concurrent sightings resulted in 33.7 whales per 1000 km2 (CV 0.77, 95% CI 8.9-50.5). Cue-count PAM methods under application provide reliable estimates of beaked whale density, over relatively long time periods and in realistic scenarios, as these match the concurrent density estimates obtained from visual observations.


Assuntos
Ecolocação , Baleias , Animais , Vocalização Animal , Espanha , Espectrografia do Som , Fatores de Tempo , Acústica
2.
ESMO Open ; 7(6): 100612, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375271

RESUMO

Alectinib is a preferred first-line therapy for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in several national clinical practice guidelines. The randomized, global, phase III ALEX study has demonstrated significant improvement in progression-free survival for alectinib over crizotinib in treatment-naive ALK-positive NSCLC. It was also the first study to show clinically meaningful improvement in overall survival for a next-generation ALK tyrosine kinase inhibitor relative to crizotinib. The J-ALEX and ALESIA phase III studies confirmed the clinical benefit of alectinib relative to crizotinib in the first-line ALK-positive NSCLC treatment setting in Japanese and Asian patients, respectively. Across these pivotal phase III trials, alectinib had a manageable, well-characterized safety profile. Here, we review the safety and tolerability of long-term alectinib treatment in patients with advanced ALK-positive NSCLC and provide guidance for physicians, based on clinical experience, on the management of the most frequently reported adverse events (AEs). Most AEs associated with alectinib can be managed by dose reduction. Some alectinib-related AEs are not yet fully characterized, including myalgia and peripheral oedema and deciphering their underlying mechanism of action could enhance their management. With longer-term follow-up, the safety profile of alectinib continues to remain consistent in the ALEX study, with no new safety signals observed. Safety and tolerability data from the first-line phase III alectinib trials are also consistent with those observed in clinical trials of alectinib in later-line settings. These results add to the weight of evidence recommending alectinib as a preferred therapy for treatment-naive advanced ALK-positive NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/patologia , Quinase do Linfoma Anaplásico , Inibidores de Proteínas Quinases/efeitos adversos , Receptores Proteína Tirosina Quinases/uso terapêutico
3.
ESMO Open ; 7(4): 100500, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35753086

RESUMO

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Infecções por Papillomavirus , Fibrose , Humanos , Inibidores de Checkpoint Imunológico , RNA Mensageiro , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular
5.
ESMO Open ; 7(1): 100333, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35042152

RESUMO

BACKGROUND: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling. PATIENTS AND METHODS: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes. RESULTS: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93). CONCLUSIONS: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Piperidinas
6.
Dig Liver Dis ; 54(5): 635-641, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34862115

RESUMO

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Doença Crônica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Sistema de Registros
7.
Clin Transl Oncol ; 23(1): 5-9, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32447647

RESUMO

The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.


Assuntos
COVID-19/patologia , Sistemas Eletrônicos de Liberação de Nicotina , Vaping/efeitos adversos , COVID-19/epidemiologia , Suscetibilidade a Doenças , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Humanos , Macrófagos/metabolismo , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/patologia , Risco , SARS-CoV-2 , Vaping/epidemiologia , Adulto Jovem
8.
Food Res Int ; 136: 109594, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32846619

RESUMO

There is a growing interest in the identification of chemometric markers that allow the distinction and authentication of dark-chocolates according to their cocoa geographical origin and/or genotype. However, samples derived from Latin American cocoa, including specimens from North and South America, have not been studied in this context. An exploration of the melting behavior, fat composition, bioactive content, and volatile profile of commercial darkchocolates was conducted to identify possible patterns related to the genotype and/or origin of cocoa from Latin America. The melting properties were evaluated by DSC and related to fat content and fatty acids profile. Total polyphenol, anthocyanin, methylxanthine, and catechin content were analyzed. Finally, the volatile compounds were extracted and identified by HS-SPME/GC-MS and were analyzed through Principal Component Analysis (PCA) and the Hierarchical Cluster Analysis Heatmap (HCA Heatmap). The fatty acids profile showed a relationship with the melting properties of dark chocolate. The samples exhibited two glass-transition temperatures (Tg) at ≈19 °C and ≈25.5 °C, possibly related to traces of unstable polymorphic forms of monounsaturated triacylglycerides. The analysis of bioactive compounds demonstrated great variability among samples independent of the cocoa origin, genotype, and content. The PCA and HCA Heatmaps allowed discriminating against the chocolates in relation to the cocoa origin and genotype. Compounds like tetramethylpyrazine, trimethylpyrazine, benzaldehyde, and furfural could be considered as dark-chocolate aroma markers derived from Latin American cocoas (North American region). The 2-phenylethyl alcohol, 2-methylpropanoic acid, 2,3-butanediol, 2-nonanone, and limonene for derived from South America. And the 2-phenylethyl acetate, 3-methyl-butanal, and cinnamaldehyde could allow to distinguishing between regional genotypes.


Assuntos
Cacau , Chocolate , Genótipo , América Latina , América do Sul
9.
Heliyon ; 6(3): e03632, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32258479

RESUMO

The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols. Interactome of these compounds with thirteen target proteins involved in type 2 diabetes mellitus was performed in-silico. In total, 312 bioactive compounds/protein interaction analyses were acquired. Molecular docking results highlighted that nine of the top ten interactions correspond to anthocyanins, cyanidin 3-glucoside with 11ß-HS, GFAT, PPARG; delphinidin 3-glucoside with 11ß-HS, GFAT, PTP and RTKs; and petunidin 3-glucoside with 11ß-HS and PTP. These proteins are involved in mechanisms regulating functions such as inflammation, insulin resistance, oxidative stress, glucose and lipid metabolism. In conclusion, this work provides a prediction of the potential molecular mechanism of black bean and blue corn polyphenols, specifically anthocyanins and could constitute new pathways by which compounds exert their antidiabetic benefits.

10.
Ann Oncol ; 31(4): 525-531, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32115349

RESUMO

BACKGROUND: Preclinical data have shown that proton pump inhibitors (PPI) can modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized controlled trial data are lacking. This pooled analysis evaluated the effect of ATB and PPI on outcome in patients randomized between ICI and chemotherapy. PATIENTS AND METHODS: This retrospective analysis used pooled data from the phase II POPLAR (NCT01903993) and phase III OAK (NCT02008227) trials, which included 1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly assigned to receive atezolizumab (n = 757) or docetaxel (n = 755). The main objective of this analysis was to assess the impact of ATB and PPI use on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 169 (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. Multivariate analysis in all patients revealed that ATB were associated with shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 1.32, 95% CI 1.06-1.63, P = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 1.20-1.75, P = 0.0001). PPI use was associated with shorter PFS in the atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, P = 0.001). There was no association between ATB and PPI use and PFS or OS within the docetaxel population. CONCLUSION: In this unplanned analysis from two randomized trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is associated with poor outcome and may influence the efficacy of ICI.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antibacterianos , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores da Bomba de Prótons , Estudos Retrospectivos
11.
PLoS One ; 14(6): e0216658, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170163

RESUMO

BACKGROUND: There are limited data about the role of endoscopic ultrasound-guided tissue acquisition (EUS-TA), by fine needle aspiration (EUS-FNA) or biopsy (EUS-FNB), in the evaluation of the adrenal glands (AG). The primary aim was to assess the diagnostic yield and safety. The secondary aims were the malignancy predictors, and to create a predictive model of malignancy. METHODS: This was a retrospective nationwide study involving all Spanish hospitals experienced in EUS-TA of AGs. Inclusion period was from April-2003 to April-2016. Inclusion criteria: all consecutive cases that underwent EUS-TA of AGs. EUS and cytopathology findings were evaluated. Statistical analyses: diagnostic accuracy of echoendoscopist's suspicion using cytology by EUS-TA, as gold standard; multivariate logistic regression model to predict tumor malignancy. RESULTS: A total of 204 EUS-TA of AGs were evaluated. Primary tumor locations were lung70%, others19%, and unknown11%. AG samples were adequate for cytological diagnosis in 91%, and confirmed malignancy in 60%. Diagnostic accuracy of the endosonographer's suspicion was 68%. The most common technique was: a 22-G (65%) and cytological needle (75%) with suction-syringe (66%). No serious adverse events were described. The variables most associated with malignancy were size>30mm (OR2.27; 95%CI, 1.16-4.05), heterogeneous echo-pattern (OR2.11; 95%CI, 1.1-3.9), variegated AG shape (OR2.46; 95%CI, 1-6.24), and endosonographer suspicion (OR17.46; 95%CI, 6.2-58.5). The best variables for a predictive multivariate logistic model of malignancy were age, sex, echo-pattern, and AG-shape. CONCLUSIONS: EUS-TA of the AGs is a safe, minimally invasive procedure, allowing an excellent diagnostic yield. These results suggest the possibility of developing a pre-EUS procedure predictive malignancy model.


Assuntos
Glândulas Suprarrenais/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias das Glândulas Suprarrenais/patologia , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Feminino , Humanos , Masculino , Análise Multivariada , Estudos Retrospectivos , Segurança
12.
Aliment Pharmacol Ther ; 50(3): 278-288, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31222872

RESUMO

BACKGROUND: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM: To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS: Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION: This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.


Assuntos
Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Estudos de Coortes , Doença de Crohn/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Indução de Remissão/métodos , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento
13.
Clin Transl Oncol ; 21(10): 1364-1373, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30798512

RESUMO

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carmustina/uso terapêutico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Antígeno AC133/genética , Antígeno AC133/metabolismo , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Carmustina/efeitos adversos , Proteína 1 Semelhante à Quitinase-3/genética , Colômbia , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Esquema de Medicação , Feminino , Genes erbB-1 , Genes p53 , Glioblastoma/irrigação sanguínea , Glioblastoma/genética , Glioblastoma/mortalidade , Humanos , Isocitrato Desidrogenase/genética , Masculino , Metilação , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/irrigação sanguínea , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , RNA Mensageiro/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Análise de Sobrevida , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
14.
Clin Transl Oncol ; 20(12): 1529-1537, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29737461

RESUMO

PURPOSE: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. PATIENTS AND METHODS: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. RESULTS: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. CONCLUSION: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.


Assuntos
Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante/métodos , Glioblastoma/terapia , Radioterapia/métodos , Tempo para o Tratamento , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia/métodos , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Resultado do Tratamento
15.
Ann Oncol ; 29(6): 1409-1416, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29668860

RESUMO

Background: This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. Patients and methods: ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS). Results: Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9-12.2] with alectinib and 1.4 months (95% CI: 1.3-1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08-0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1 months (95% CI: 6.3-10.8) with alectinib and 1.6 months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks). Conclusion: Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile. Trial registration: ClinicalTrials.gov NCT02604342; Roche study MO29750.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Salvação , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbazóis/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias do Sistema Nervoso Central/secundário , Crizotinibe/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem , Piperidinas/administração & dosagem , Prognóstico , Taxa de Sobrevida
16.
Rev. CES psicol ; 10(2): 17-27, jul.-dic. 2017. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-896565

RESUMO

Resumen Objetivo. Evaluar las evidencias de validez del Mini Mental State Examination que sustentan su interpretación en adultos mayores. Métodos. Estudio de fuente secundaria con la participación de 4034 adultos mayores residentes de Antioquia, Colombia, 2012. Se siguieron los lineamientos de Wolfe y Smith para análisis desde el modelo Rasch. Resultados. Se identificó dependencia local entre los ítems de atención y cálculo. Estos producen una segunda medida que afecta la unidimensionalidad del instrumento. La confiabilidad de los ítems fue de 0,80, la medida explicó el 45,2% de la varianza de las puntuaciones crudas. Conclusión. Los resultados sugieren diferenciar las habilidades de atención y cálculo de los demás procesos cognitivos considerados por el instrumento. El MMSE presenta limitaciones de validez de generalización que potencialmente afectan comparaciones transculturales.


Abstract Objective. To evaluate validity of the Mini-Mental State Examination (MMSE) that supports the interpretability in older adults. Methods. Secondary data study administered in 4.034 older adults in Antioquia, Colombia, 2012. Data were analyzed from Rasch models according to Wolfe and Smith guidelines. Results. Attention and calculation items showed local dependency. They produce a second relevant measure affecting the unidimensional type of the test. The reliability of the items was of 0.80, the measure explained 45.2% of the raw score variance. Conclusion. Results suggest differentiating attention and calculation abilities from the other cognitive processes considered by the test. MMSE shows generalization validity limitations that may affect transcultural comparisons.

17.
Ces med. vet. zootec ; 12(2): 123-133, mayo-ago. 2017. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-890061

RESUMO

Resumen El objetivo de este estudio fue evaluar las características clínicas del loxoscelismo dermonecrótico (LDN) en equinos del departamento de Córdoba, Colombia. El estudio, fue de tipo descriptivo, no probabilístico, las muestra fueron seleccionadas por conveniencia. Se utilizaron nueve caballos criollos (Equus ferus caballus) y dos burros (Equus asinus africanus) con LDN diagnosticados clínica e histopatológicamente en diferentes producciones del Departamento. Al describir las lesiones cutáneas, éstas se caracterizaron por la presencia de una severa dermatitis necrótica, con edema y un área eritematosa focal, al detallar el área lesionada, se observó un punto necrótico central y dos halos alrededor (un halo blanco medial y un halo violáceo más externo) en la mayoría de los casos estudiados; así como ausencia de signos neurológicos y sistémicos. Las lesiones se ubicaron en la mayoría de los casos a nivel dorsal, seguido de la región rostral, pecho y pene. Histopatológicamente en la coloración de Hematoxilina Eosina (H&E), se observó severa dermatitis piogranulomatosa, con marcada infiltración de polimorfonucleares especialmente neutrófilos, con vacuolización de la capa basal de la epidermis y edema en la unión dermo-epidérmica. El diagnóstico definitivo de LDN en los 11 animales estudiados, se fundamentó en las manifestaciones clínicas observadas, las características anatomopatológicas de las lesiones y los resultados histopatológicos. El presente informe constituye el primer reporte de LDN en el Departamento de Córdoba, ya que no se encontraron reportes en la literatura consultada.


Abstract The aim of this study was to characterize the clinical aspects of dermonecrotic loxoscelism (LDN) in horses department of Cordoba, Colombia. This study was descriptive, not probabilistic, in animals of convenience. Nine horses (Equus ferus caballus) and 2 donkeys (Equus asinus africanus) were used with LDN diagnosed clinically and histopathologically in different productions of the Department. When describing the skin lesions, these were characterized by the presence of severe necrotic dermatitis, with edema and a focal erythematous area, when detailing the injured area, a central necrotic spot and two halos around it (a medial white halo and a halo Violet) in most of the cases studied; As well as absence of neurological and systemic signs. The lesions were located in most cases at the dorsal level, followed by the rostral region, chest and penis. Histopathologically in the staining of Hematoxylin Eosin (H & E), severe piogranulomatous dermatitis was observed, with marked infiltration of polymorphonuclear cells especially neutrophils, with vacuolization of the basal layer of the epidermis and edema in the dermo-epidermal junction. The definitive diagnosis of LDN in the 11 animals studied was based on the clinical manifestations observed, the anatomopathological characteristics of the lesions and the histopathological results. The present report constitutes the first LDN report in the Department of Córdoba, since no reports were found in the consulted literature.


Resumo O objetivo deste estudo foi caracterizar os aspectos clínicos da loxoscelismo dermonecrótica (LDN) em equinos de Córdoba, Colômbia. Este estudo foi descritivo, não probabilístico, em animais de conveniência. Foram usados 9 cavalos (Equus ferus caballus) e 2 jumentos (Equus asinus africanus) com LDN clinicamente e histologicamente diagnosticado no Departamento diferentes produções. Ao descrever as lesões da pele, que foram caracterizados pela presença de dermatite necrotizante grave, edema e focal área eritematosa, detalhando a área lesionada, um ponto necrótico central e dois halos foram observados em torno de (halo branco medial e halo mais exterior) violáceo, na maioria dos casos estudados; e ausência de sinais neurológicos e sistémicas. As lesões foram localizados na maioria dos casos ao nível dorsal, seguida da rostral, peito e do pénis. Foi observada histologicamente em hematoxilina-eosina (H & E), dermatite piogranulomatosa grave, com infiltração acentuada de neutrófilos polimorfonucleares especialmente com vacuolização da camada basal da epiderme e edema na junção dermo-epidérmica. O diagnóstico definitivo da LDN nos 11 animais estudados foi baseado nas manifestações clínicas observadas, características histopatológicas de lesões e os resultados histopatológicos. O presente relatório constitui o primeiro relatório LDN no Departamento de Córdoba, uma vez que não foram encontrados relatórios na literatura consultada.

18.
Rev. mex. ing. bioméd ; 38(1): 103-114, ene.-abr. 2017. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-902331

RESUMO

Resumen: Las colágenas son cada día más atractivas en la fabricación de andamios para Ingeniería de Tejidos, por su biocompatibilidad, manejo y capacidad de producirlas industrialmente. El objetivo del presente artículo fue presentar un análisis sobre el avance en la investigación, el desarrollo y producción de colágenas recombinantes de humano, los sistemas de producción y sus usos en Ingeniería de Tejidos. Se realizó una revisión de la literatura científica internacional arbitrada en bases de datos como Scopus, PubMed y Google Académico y se empleó aquella relevante a nuestro objetivo. Se encontró que el desarrollo de colágenas recombinantes de humano muestra un avance significativo y en la actualidad los sistemas de expresión, como bacterias y plantas, presentan ventajas sobre la calidad de la estructura y la biocompatibilidad, aunque con rendimientos todavía bajos. Mientras que existe escasa información sobre sus aplicaciones en Ingeniería de Tejidos, principalmente cartílago y hueso, en modelos animales y estudios clínicos. En las fuentes de información no se incluyeron patentes, por lo que nuestros hallazgos están limitados a publicaciones científicas. El presente trabajo, presenta los avances más recientes sobre la ingeniería de colágenas recombinantes y sus aplicaciones biomédicas en fabricación de tejidos con potencial uso clínico. Por lo que su factibilidad en la medicina regenerativa es prometedor y se requiere mayor investigación que permita su aplicación en un futuro cercano.


Abstract: Due to its biocompatibility, handling and industrial production capacity, collagens have been increasingly attractive in the manufacture of scaffolds for Tissue Engineering. The aim of the present work was to present an analysis on the progress in research, development and production of human recombinant collagens, expression systems and their uses in Tissue Engineering. A review of the international scientific peer-reviewed literature in databases such as Scopus, PubMed and Google Scholar was done and that relevant to our objective was employed. The development of human recombinant collagens was found to be significant, and currently the expression systems, like bacteria and plants, show advantages over structure quality and biocompatibility, albeit with still restricted yields. However, there is narrow information about its applications in Tissue Engineering, mostly studied for cartilage and bone, in animal models and clinical studies. We did not include patents in the study, thus our findings are limited to scholar data. The present work presents the most recent advances in the engineering of recombinant collagens and their biomedical applications in the manufacture of tissues with potential clinical applications. The potential of recombinant collagens in regenerative medicine is promising and more research is needed that might allow a broad application in the near future.

19.
Ces med. vet. zootec ; 11(3): 48-57, jul.-dic. 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-952551

RESUMO

The blood glucose level is an important parameter for clinical dedicated to equine neonatology, especially in neonatal care units, where is critical as a prognostic indicator parameter, so you need to have parameters precise reference to assist the decision making. In the race Criollo Colombiano we have not found reference values, so in clinical practice are used values for different races and backgrounds, and this is the first report in this race in Colombia. The study was conducted in the municipality of Bolivar City; where blood glucose levels were assessed in peripheral blood sample using a portable glucometer. They were evaluated 29 infants children foals stabled mares, measurements were made before the first lactation (T0) and three measurements at intervals of three hours. (T3, T6 and T9). Confidence intervals for the population mean were determined, and a comparison was made between the sexes, a regression equation for predicting glucose was also determined by the measurement time. T0 was determined that an average of 81.76 ± 9.25 mg / dL, was presented to the T3 was 88.97 ± 11.73 mg / dL, for the T6 112.31 ± 16.52 mg / dL and T9 118.52 ± 13.59 was mg / dL. Polynomial regression equation was Glucose = 80.27 + 1.617 tiempo2-0,127tiempo3 (R2 = 0.58). No statistically significant difference (p> 0.05) was found between the sexes.


El nivel de glicemia es un parámetro importante para el clínico dedicado a la neonatología equina, especialmente en las unidades de cuidados neonatales, en las cuales es un parámetro crítico como indicador pronóstico, por lo que es necesario tener parámetros de referencia precisos que ayuden a la toma de decisiones. En la raza Criollo Colombiano no se han encontrado valores de referencia, por lo que en la práctica clínica son usados valores establecidos para razas y ambientes diferentes, siendo este el primer reporte en esta raza en Colombia. El estudio se desarrolló en el municipio de Ciudad Bolívar; en donde se evaluaron los niveles de glicemia en muestra de sangre periférica mediante un glucómetro portátil. Fueron evaluados 29 potros neonatos hijos de yeguas estabuladas, se realizaron mediciones antes de la primera lactancia (T0) y tres mediciones más con intervalos de tres horas. (T3, T6 y T9). Se determinaron los intervalos de confianza para la media poblacional, y se realizó una comparación entre sexos, también se determinó una ecuación de regresión para la predicción de la glucosa según el tiempo de medición. Se determinó que al T0 se presentó una media de 81,76 ± 9,25 mg/dL, para el T3 fue de 88,97 ± 11,73 mg/dL, para el T6 de 112,31 ± 16,52 mg/dL y para el T9 fue de 118,52 ± 13,59 mg/dL. La ecuación de regresión polinómica fue Glucosa = 80,27+1,617 tiempo2- 0,127tiempo3 (R2 =0,58). No se encontró diferencia estadísticamente significativa (p>0,05) entre los sexos.


O nível de açúcar no sangue é um parâmetro importante para clínico dedicado a neonatologia equino, especialmente em unidades de cuidados neonatais, onde é crítica como um parâmetro indicador de prognóstico, por isso você precisa ter parâmetros de referência precisos para ajudar o tomada de decisã o. Na corrida Criollo Colombiano nã o foram encontrados valores de referência, de modo que na prática clínica sã o os valores usados para diferentes raças e origens, e este é o primeiro relatório nesta corrida na Colô mbia. O estudo foi realizado no municipalidades de Ciudad Bolívar; onde os níveis de glicose no sangue foram avaliados em amostra de sangue periférico usando um glicosímetro portátil. Foram avaliadas 29 crianças crianças potros éguas estabulados, as medidas foram feitas antes da primeira lactaçã o (T0) e três medições em intervalos de três horas. (T3, T6 e T9). foram determinados intervalos de confiança para a média da populaçã o, e foi feita uma comparaçã o entre os sexos, uma equaçã o de regressã o para a previsã o de glicose também foi determinada pelo tempo de mediçã o. T0 foi determinado que uma média de 81,76 ± 9,25 mg / dL, foi apresentada para a T3 era 88,97 ± 11,73 mg / dL, para a T6 112,31 ± 16,52 mg / dL e T9 118,52 ± 13,59 era mg / dL. equaçã o de regressã o polinomial foi Glucose = 80,27 + 1.617 tempo 2-0,127 tempo 3 (R2 = 0,58). Nã o foi encontrada diferença estatisticamente significativa (p> 0,05) entre os sexos..

20.
Ces med. vet. zootec ; 11(3): 104-112, jul.-dic. 2016. ilus
Artigo em Espanhol | LILACS | ID: biblio-952555

RESUMO

The aim of this study was to describe the clinical, gross and microscopic lesions as diagnostic methods pemphigus foliaceus (PF) in an imported horse Silla Argentino, castrated male, 9 years old from the municipality of Montería (Córdoba, Colombia). In describing the clinical case, the presence of scabs generalized mainly at the level of the chest and abdomen, initially presented ventral edema and some areas had pustules and vesicles, as well as fever and marked pruritus was observed. The lesions were located bilaterally at the level of face, thoracic region, abdominal, gluteal and limbs. Histopathological in the HE stain, was observed the presence of acantholytic keratinocytes and areas acantholytic sloughing in the granular layer, hyperplasia and epidermal desquamation; areas subepidermal spongiosis and various subcorneal pustules characterized by the presence of intact neutrophils and degenerate and dermal edema hyalinization moderate collagen, likewise in TG staining, poor dermal collagen proliferation disorganized with little presence of diffuse connective tissue was observed, while in the PR/P staining, areas of red birefringence was observed, indicating moderate presence of mature type I collagen (red bright polarization). The diagnosis was based on clinical signs, histopathological findings, differential diagnosis and response to medical treatment. In the literature there are no reports of PF in the Department, so it is the first report of this disease in horses of Córdoba.


El objetivo de este estudio fue describir las manifestaciones clínicas, lesiones macro y microscópicas como métodos de diagnóstico del pénfigo foliáceo (PF) en un caballo importado Silla Argentino, macho entero, de 9 años de edad, procedente del municipio de Montería (Córdoba, Colombia). Al describir el caso clínico, se observó presencia de costras generalizadas principalmente a nivel de tórax y abdomen, inicialmente presentó edema ventral y algunas zonas presentaron pústulas y vesículas, así como fiebre y prurito marcado. Las lesiones se ubicaron en forma bilateral, a nivel de rostro, región torácica, abdominal, glútea y extremidades. Histopatológicamente en la coloración de HE, se observó la presencia de queratinocitos acantolíticos y áreas de esfacelación acantolítica en la capa granulosa, Hiperplasia y descamación epidérmica, áreas de espongiosis subepidérmica y diversas pústulas subcórneas caracterizadas por la presencia de neutrófilos íntegros y degenerados y edema dérmico con moderada hialinización del colágeno, así mismo en la tinción de T-G, se observó escasa proliferación dérmica de colágeno desorganizados con escasa presencia de tejido conjuntivo difuso, mientras que en la tinción de P-R/P, se observó áreas de birrefringencia rojiza, indicando moderada presencia de colágeno maduro tipo I (color rojo brillante en la polarización). El diagnóstico se fundamentó en los signos clínicos, hallazgos histopatológicos, diagnóstico diferencial y respuesta al tratamiento médico. En la literatura consultada no existen reportes de PF en el Departamento, por lo que es el primer reporte de esta enfermedad en caballos de Córdoba.


O objetivo deste estudo foi descrever as lesões clínicas, macroscópicas e microscópicas como métodos de diagnóstico do pénfigo foliaceo (PF) num cavalo importado Argentino, macho, de 9 anos de idade do município de Montería (Córdoba, Colô mbia). Ao descrever o caso clínico, observou-se a presença de crostas generalizadas, principalmente ao nível do tórax e do abdómen, inicialmente apresentaram edema ventral e algumas áreas tinham pústulas e vesículas, bem como febre e prurido marcado. As lesões eram localizadas bilateralmente, a altura da face, regiã o torácica, abdominal, glúteos e membros. Foi observada na histopatologia na coloraçã o de HE, a presença de queratinócitos acantolíticos e áreas de descamaçã o acantolíticas na camada granular, hiperplasia e descamaçã o da epiderme, áreas de espongiose subepidermal e várias pústulas subcórneas caracterizados pela presença de neutrófilos intactos e degenerados, edema dérmico moderado e hialinizaçã o de colágeno, também na coloraçã o T-G, observou-se pobre proliferaçã o de colágeno dérmico desorganizado com pouca presença de tecido conjuntivo difuso, enquanto na coloraçã o de PR/P, observou-se a presença de áreas de birrefringência avermelhada, indicando presença moderada de colágeno tipo I maduro (vermelho brilhante na polarizaçã o). O diagnóstico foi baseado nos sinais clínicos, achados histopatológicos, diagnóstico diferencial e resposta ao tratamento médico. Na literatura nã o há relatos de PF no Departamento, por isso é o primeiro relato da doença em cavalos de Córdoba.

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