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1.
Kidney Blood Press Res ; 48(1): 785-790, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37778341

RESUMO

INTRODUCTION: The association of APOL1 risk variants with cardiovascular risk and cardiovascular disease (CVD) in observational and clinical trials has had inconsistent results. We aim to assess the relationship between the presence of APOL1 risk variants and the CVD risk in Afro-descendant patients with end-stage renal disease (ESRD). METHODS: We performed an observational, cross-sectional study of Afro-descendant adult patients with ESRD who were on the waitlist for a kidney transplant. Associations of APOL1 genotypes (high-risk [HR] = 2 alleles; low-risk [LR] = 0 or 1 allele) with cardiovascular risk were the primary clinical endpoint. The relation was evaluated using univariate and multivariate analysis. RESULTS: We enrolled a total of 102 patients with ESRD; 37% (38 patients) had APOL1 HR status with two alleles in homozygous (G1/G1 = 21 and G2/G2 = 3) or compound heterozygote (G1/G2 = 14) form and 63% (64 patients) had APOL1 LR status. No significant association was found between HR APOL1 genotypes and high cardiovascular risk (in adjusted Colombia Framingham Risk Score). APOL1 HR versus LR variants were not independently associated with left ventricular hypertrophy or systolic dysfunction. No cardiovascular deaths occurred during the follow-up. CONCLUSION: In Afro-descendent patients with ESRD, APOL1 HR status is not associated with the increase in cardiovascular risk profile and metabolic disturbances.


Assuntos
Apolipoproteína L1 , Doenças Cardiovasculares , Falência Renal Crônica , Adulto , Humanos , Apolipoproteína L1/genética , Doenças Cardiovasculares/genética , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Falência Renal Crônica/genética , Fatores de Risco , População Negra
2.
Emerg Infect Dis ; 25(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31743085

RESUMO

In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Vaccinia virus , Vacínia/epidemiologia , Vacínia/virologia , Zoonoses/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agricultura , Animais , Criança , Colômbia/epidemiologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Orthopoxvirus/imunologia , Fatores de Risco , Estudos Soroepidemiológicos , Vaccinia virus/imunologia , Adulto Jovem
3.
Br J Cancer ; 116(6): 802-810, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28170370

RESUMO

BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma. We evaluated the panel performance in three steps. First, we analysed its analytical sensitivity on cell line DNA and by using an artificial reference standard with multiple mutations in different genes. Second, we analysed cfDNA from cancer patients at presentation (n=42), treatment response (n=12) and tumour progression (n=11); all patients had paired tumour tissue and cfDNA previously genotyped with a Taqman-derived assay (TDA). Third, we tested blood samples prospectively collected from NSCLC patients (n=79) to assess the performance of SiRe in clinical practice. RESULTS: SiRe had a high analytical performance and a 0.01% lower limit of detection. In the retrospective series, SiRe detected 40 EGFR, 11 KRAS, 1 NRAS and 5 BRAF mutations (96.8% concordance with TDA). In the baseline samples, SiRe had 100% specificity and 79% sensitivity relative to tumour tissue. Finally, in the prospective series, SiRe detected 8.7% (4/46) of EGFR mutations at baseline and 42.9% (9/21) of EGFR p.T790M in patients at tumour progression. CONCLUSIONS: SiRe is a feasible NGS panel for cfDNA analysis in clinical practice.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Colorretais/genética , DNA de Neoplasias/genética , Tumores do Estroma Gastrointestinal/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Melanoma/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , DNA de Neoplasias/sangue , Feminino , Seguimentos , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/sangue , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Melanoma/sangue , Melanoma/tratamento farmacológico , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Curva ROC
4.
Eur J Surg Oncol ; 50(6): 108031, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38552416

RESUMO

INTRODUCTION: Cancer is a leading cause of morbidity and mortality worldwide, and coordinated research efforts are vital to improve global outcomes. Clinical or translational research is usually planned, coordinated and executed by clinical researchers. With this survey we aimed to identify the main hurdles in front of young clinical investigators in oncology. METHODS AND MATERIALS: An anonymized survey was distributed using social media between April and November 2022. Target population were health-care professionals in the field of oncology - physicians, nurses and researchers. We divided participants according to working experience (<40 vs. >40 years of age) and country of practice (Europeans vs. non-Europeans). RESULTS: We received 121 responses from participants practicing in 36 countries. Eighty-seven (72%) of the participants were under 40 years. Eighty-nine (74%) were from European countries and thirty-two (26%) were from non-European. Experienced and European professionals were more likely to be involved in all different aspects of clinical trials. The main source of funding - independently of geographic location - were industry grants. Investigators out of Europe have less participation in international grants. Over 50% of participants dedicate time for clinical research from their personal time and are not paid for it. Almost 50% of investigators don't have access to an experienced mentor in their institution. CONCLUSION: The majority of respondents to our survey are active clinical researchers. Our data indicate that access to education and training as well as possibilities for appropriate networking, and specifically lack of mentorship, are key limiting factors in developing clinical research by healthcare professionals.


Assuntos
Oncologia , Pesquisadores , Humanos , Inquéritos e Questionários , Adulto , Pesquisa Biomédica , Feminino , Masculino , Europa (Continente) , Apoio à Pesquisa como Assunto , Pessoa de Meia-Idade , Mentores
5.
J Med Case Rep ; 13(1): 144, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31088573

RESUMO

BACKGROUND: Endothelial growth factor receptor (EGFR) mutations are an essential driver of personalized therapy for patients with lung cancer and are detected in approximately 15% of Caucasian and 50% of Asian patients. EGFR tyrosine kinase inhibitors have been developed and used for this set of patients. T790M mutation in exon 20 is usually associated with secondary resistance to EGFR tyrosine kinase inhibitors therapy but is also present in treatment-naïve patients. The frequency for baseline T790M mutation varies from 4 to 35% according to the detection method used. Newer techniques have yielded higher rates, but concerns about false-positive results have been raised. Compound mutations account for 4-14% of all EGFR-mutated tumors, with no studies yet to provide a frequency rate for T790M + 19 deletion association due to the small number of cases. However, there are reports that pretreatment T790M + L858R association is significantly more frequent compared to T790M + exon 19 deletion mutations. Diagnostic challenges, current knowledge on the subject, and therapeutic decisions are discussed. CASE PRESENTATION: We present the case of a 43-year-old Hispanic woman, a treatment-naïve patient, with metastasized lung cancer adenocarcinoma harboring a T790M deletion along with the classic 19 mutation. The initial symptoms were monoparesis of her left leg, associated with hyperreflexia, and hypoesthesia. In the absence of third-generation tyrosine kinase inhibitors, a platinum-based therapy was initiated with no response and she died 4 months after diagnosis. CONCLUSIONS: Osimertinib seems to be a suitable therapy for treatment-naïve patients with sensitizing and resistant compound EGFR mutations. More studies regarding the clinical characteristics of these patients and the appropriate management of this condition are needed to provide the highest standard of care.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Ósseas/secundário , Hipestesia/patologia , Extremidade Inferior/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Análise Mutacional de DNA , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Éxons , Evolução Fatal , Feminino , Humanos , Hipestesia/diagnóstico por imagem , Hipestesia/etiologia , Extremidade Inferior/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética , Inibidores de Proteínas Quinases/uso terapêutico , Reflexo Anormal , Deleção de Sequência
7.
BMC Cancer ; 7: 28, 2007 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-17288606

RESUMO

BACKGROUND: Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60-70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels > or =200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. METHODS: We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein > or = 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. RESULTS: For an elevation of alpha fetoprotein > or= 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate > or =7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. CONCLUSION: The progressive elevation of alpha fetoprotein > or =7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach alphaFP levels > or =200 ng/mL. Prospective studies are required to confirm this observation.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Cirrose Hepática/sangue , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/sangue , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
8.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1536043

RESUMO

Contexto: los pacientes con trasplante de riñón parecen tener un riesgo particularmente alto de enfermedad grave por COVID-19 debido a la inmunosupresión y la presencia de comorbilidades. Objetivo: describir las características clínicas, paraclínicas y desenlaces de los pacientes trasplantados renales que presentan infección por SARS-COV-2 en un hospital de cuarto nivel en Cali, Colombia. Metodología: realizamos un estudio observacional de receptores de trasplante renal con infección por SARS-CoV-2 ingresados ​​en la Fundación Valle del Lili, de junio a diciembre del 2020. Para ser elegibles en el estudio, los pacientes debían presentar síntomas compatibles, RT-PCR positiva y manejo hospitalario. Se excluyó a los pacientes asintomáticos. Resultados: inscribimos a un total de 50 pacientes, donde el 64 % eran hombres y la edad media fue de 53,5 años (rango 46-60). Las comorbilidades fueron: 36 (70 %) con hipertensión, 16 (32 %) con diabetes mellitus y 5 (10 %) con obesidad y los regímenes inmunosupresores más comunes fueron: tacrolimus, micofenolato y prednisona. La mediana de tiempo desde el inicio de los síntomas hasta la RT-PCR positiva fue de siete días. Los síntomas iniciales más comunes fueron fiebre (64 %), fatiga (58%), tos (44%) y disnea (36%). Los niveles basales de proteína C reactiva (PCR) fueron de 6,43 mg/dl (3,25-11,22), la mediana del recuento de linfocitos fue de 785 mm3/uL (550-1230), el dímero D basal fue de 0,767 ug/ml (0,484-1153,5) y el nivel medio de ferritina fue de 1011 ng/ml (670-2145). El 40 % desarrolló lesión renal aguda (20 pacientes), de los cuales 11 pacientes necesitaron terapia de remplazo renal, 6 de los pacientes fallecieron (12 %), 4/6 por insuficiencia multiorgánica relacionada con la sepsis y 2/6 por el síndrome de dificultad respiratoria agudo (SDRA). Conclusiones: las complicaciones mayores como la lesión renal aguda, el síndrome de dificultad respiratoria aguda y la mortalidad relacionada con la infección por COVID-19 observadas en nuestro estudio son significativas, pero menos frecuentes que las reportadas en otros países.


Background: Patients with kidney transplants seem to be at particularly high risk for severe COVID19 disease due to their impaired immune responses and comorbidities. Purpose: This study aims to describe kidney transplant patients' clinical characteristics and outcomes with SARSCOV-2 infection in a fourth-level hospital in Cali, Colombia. Methodology: We performed an observational study of kidney transplant recipients with SARS-CoV2 infection admitted at Fundación Valle del Lili from June to December 2020. To be eligible for this study, patients have symptoms compatible, a positive RT-PCR and inpatient management. Asymptomatic patients were excluded. Results: We enrolled a total of 50 patients. 64% were male, and the median age was 53.5 years (range 46-60). The comorbidities were 36 (70%) hypertension, 16 (32%) diabetes mellitus, 5 (10%) obesity. The most common immunosuppressive regimen was tacrolimus, mycophenolate and prednisone. The median time from symptoms onset to the positive RT-PCR was 7 days. The most common initial symptom was fever (64%), and fatigue (58%), cough (44%) and dyspnea (36%). Baseline levels of CRP was 6.43 mg/dL (3.25-11.22). The median lymphocyte count was 785 mm3/uL (550-1230). Baseline D-Dimer was 0.767 ug/ml (0.484-1153.5), ferritin median level was 1011ng/ml (670-2145). Six of the patients died (12%), 4/6 were by sepsis-related multi-organ failure and 2/6 were by ARDS. Conclusions: Major complications such as acute kidney injury, acute respiratory distress syndrome and mortality related to COVID-19 infection observed in our study are lower than those reported in other countries.

9.
Clin Neurol Neurosurg ; 108(7): 661-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16500745

RESUMO

BACKGROUND: Craniopharyngioma is a rare, benign epithelial brain tumor of the suprasellar region with a high rate of recurrence. Clinical and histopathological features that might be predictors of recurrence/regrowth have not been clearly delineated. METHODS: We compared recurrence/regrowth of the tumors with the clinico-pathological characteristics, vascular density, cell proliferation index, and immunohistochemical profile (cytokeratins, epithelial membrane antigen [EMA], carcinoembrionary antigen [CEA], and laminin) of 47 patients with craniopharyngioma followed for more than 5 years. RESULTS: Tumors were adamantinomatous in 42 cases (89%) and papillary squamous in 5 cases (11%). Immunoreactivity for cytokeratin 8/18/19 was positive in 64%; cytokeratin 5 in 42%; laminin 8 in 62%; and CEA in 21%. The cell proliferation index and vascular density were greater in adamantinomatous than in papillary tumors (22+/-6 versus 17+/-3, p=0.05; and 21+/-3 versus 17+/-3, p=0.037, respectively); they were neither related to recurrence nor to regrowth. No significant differences were found between adamantinomatous and papillary tumors regarding the presence of cytokeratin, laminin, CEA or glial fibrillary acidic protein (GFAP). Recurrence rate at 5 years was 59%. No relation was found between recurrence and adjuvant radiotherapy (AR). Residual tumor after surgery, whorl-like arrays (p=0.04) and immunoreactivity for p53 (p=0.022) were significantly related to recurrence/regrowth. CONCLUSIONS: Residual tumor after surgery, immunoreactivity to p53 and presence of whorl-like arrays are associated to recurrence/regrowth of craniopharyngioma.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatologia , Craniofaringioma/diagnóstico , Craniofaringioma/fisiopatologia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Antígeno Carcinoembrionário/metabolismo , Proliferação de Células , Craniofaringioma/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Laminina/metabolismo , Masculino , Mucina-1/metabolismo , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/epidemiologia , Neovascularização Patológica/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Radioterapia/estatística & dados numéricos , Proteína Supressora de Tumor p53/metabolismo
10.
Ann Hepatol ; 5(4): 263-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17151578

RESUMO

Hepatocellular carcinoma is the fifth most common malignant neoplasm worldwide. Most patients are not candidates to surgical treatment. The prognosis of this neoplasm is poor, with an overall survival rate of 8 weeks in unresectable tumors. Estrogen receptors have been found in up to 33% of this tumors, reason why treatment with tamoxifen or progesterone compounds have been tried to diminish this neoplasm's progression but its use remains controversial. In our institution, thirteen patients were treated with tamoxifen (20- 40 mg/day) and 26 received supportive measures only. The clinical and tumoral characteristics were similar in both groups. Survival in the Tamoxifen group was of 5.5 +/- 1.7 months while in the supportive measures group was of 2.1 +/- 0.5 months (p = 0.018). Other factors related to an increased survival were: female gender and the Okuda score; age, TNM and alphaFP were not related to survival. The multivariate analysis showed that treatment with tamoxifen duplicates survival independently of the tumoral stage and functional hepatic reserve. It seems that the benefit of treatment with tamoxifen is limited and is not associated to the presence of estrogen receptors. In our study a 69 year-old man with diagnosis of non-resectable hepatocellular carcinoma and negative estrogen receptors, was treated with tamoxifen with a partial response and an overall survival of 4 years until November 2005. Despite some case reports that have shown tumoral regression, while other studies do not report any survival benefits. It is important to identify patients that would benefit from treatment with tamoxifen.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Estrogênio/antagonistas & inibidores , Tamoxifeno/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Estudos Retrospectivos , Fatores Sexuais , Análise de Sobrevida , Tomografia Computadorizada por Raios X
11.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1253869

RESUMO

La tuberculosis es la primera causa de mortalidad infectocontagiosa a nivel mundial. La tuberculosis pulmonar corresponde a la presentación más frecuente, sin embargo, el 15 % de los casos cursan con infección extrapulmonar, siendo raro el compromiso amigdalino. Este reporte de caso describe a un paciente de 39 años con odinofagia recurrente secundaria a amigdalitis por Mycobacterium tuberculosis, un raro caso de tuberculosis extrapulmonar. La amigdalitis es una infección leve y frecuente de la vía aérea superior, que responde adecuadamente al manejo antibiótico; sin embargo, cuadros recurrentes y prolongados, manifestaciones atípicas o pobre respuesta a la antibioticoterapia son características que obligan a la búsqueda de diagnósticos diferenciales, lo que lleva a considerar la presencia de Mycobacterium tuberculosis como agente etiológico, especialmente en países con alto índice de tuberculosis como Colombia


Tuberculosis is the leading cause of infectious mortality worldwide. The pulmonary one corresponds to the most frequent presentation, however up to 15% of tuberculosis cases present extrapulmonary involvement, tonsillar tuberculosis being rare. The following is a case report of a 39-year-old patient with recurrent odynophagia secondary to Mycobacterium tuberculosis tonsillitis, a rare form of extrapulmonary tuberculosis. Tonsillitis is a benign and extremely common infection of the upper airway. Such patients benefit from systemic antibiotics, although, recurrent episodes, prolonged odynophagia, atypical manifestations, or poor response to antimicrobial therapy forces consideration of diagnostic possibilities other than the obvious, including Mycobacterium tuberculosis as the etiological agent, especially in countries with the highest rates of tuberculosis.


Assuntos
Humanos , Masculino , Adulto , Tuberculose Pulmonar/complicações , Tonsilite/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico por imagem , Tonsilite/tratamento farmacológico , Tonsilite/diagnóstico por imagem , Antibacterianos/uso terapêutico
12.
Transl Lung Cancer Res ; 5(1): 26-38, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26958491

RESUMO

Small cell lung cancer (SCLC) represents between 13% and 15% of all diagnosed lung cancers worldwide. It is an aggressive neoplasia, with a 5-year mortality of 90% or more. It has historically been classified as limited disease (LD) and extensive disease (ED) in most study protocols. The cornerstone of treatment for any stage of SCLC is etoposide-platinum based chemotherapy; in limited stage (LS), concomitant radiotherapy to thorax and mediastinum. Prophylactic radiotherapy to the central nervous system (CNS) [prophylactic cerebral irradiation (PCI)] has diminished the incidence of brain metastasis as the site for relapse in LD and ED patients, therefore it should be offered to patients with complete response to induction first-line treatment. Regarding second-line treatment, results are more modest and topotecan is accepted as treatment for this scenario offering a modest benefit.

13.
Transl Lung Cancer Res ; 5(5): 525-531, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27826534

RESUMO

Obtaining a biopsy of solid tumors requires invasive procedures that strongly limit patient compliance. In contrast, a blood extraction is safe, can be performed at many time points during the course disease and encourages appropriate therapy modifications, potentially improving the patient's clinical outcome and quality of life. Fusion of the tyrosine kinase genes anaplastic lymphoma kinase (ALK), C-ROS oncogen 1 (ROS 1), rearranged during transfection (RET) and neurotrophic tyrosine kinase 1 (NTRK1) occur in 1-5% of lung adenocarcinomas and constitute therapeutic targets for tyrosine kinase inhibitors. In addition, a MET splicing variant of exon 14, has been reported in 2-4% of lung adenocarcinoma and recent studies suggests that targeted therapies inhibiting MET signaling would be beneficial for patients with this alteration. In this review, we will summarize the new techniques recently developed to detect ALK, RET, ROS and NTRK1 fusions and MET exon 14 splicing variant in liquid biopsy using plasma, serum, circulating tumor cells (CTCs), platelets and exosomes as starting material.

14.
Transl Lung Cancer Res ; 5(5): 511-516, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27826532

RESUMO

Circulating free DNA (cfDNA) is obtained from serum or plasma by non-invasive methods such as a simple blood draw, a technique known as "liquid biopsy". Genetic analyses of driver alterations in cfDNA have proved very effective to predict survival and treatment response of cancer patients according to tumoral cfDNA burden in blood. Non-small cell lung cancer (NSCLC) patients with higher concentration of tumoral cfDNA in blood have, on average, shorter progression-free survival (PFS) and overall survival (OS). Regarding specific genetic alterations, KRAS proto-oncogene, GTPase (KRAS) is one of the main genes involved in NSCLC and several studies have been performed to determine its value as a predictive and prognostic biomarker in liquid biopsy. Unfortunately, to date no strong conclusions can be drawn since they have yielded contradictory results. Therefore, further investigations are necessary to establish the value of KRAS testing in liquid biopsy as prognostic or predictive factor in NSCLC. Herein, we review the current knowledge on the importance of KRAS as prognostic and predictive biomarker using non-invasive approaches and the scientific data available regarding its application in clinical practice for treatment of NSCLC.

15.
Transl Lung Cancer Res ; 5(5): 532-537, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27826535

RESUMO

Genomic analysis of circulating tumor DNA (ctDNA) released from cancer cells into the bloodstream has been proposed as a useful method to capture dynamic changes during the course of the disease. In particular, the ability to monitor epidermal growth factor receptor (EGFR) mutation status in cell-free circulating DNA (cfDNA) isolated from advanced non-small cell lung cancer (NSCLC) patients EGFR can help to the correct management of the disease and overcome the challenges associated with tumor heterogeneity and insufficient biopsied material to perform key molecular diagnosis. Here, we report a case of long term monitorization of EGFR mutation status in cfDNA from peripheral blood in an NSCLC patient in, with excellent correlation with clinical evolution.

16.
Front Med (Lausanne) ; 3: 69, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28066769

RESUMO

Liquid biopsy analyses are already incorporated in the routine clinical practice in many hospitals and oncology departments worldwide, improving the selection of treatments and monitoring of lung cancer patients. Although they have not yet reached its full potential, liquid biopsy-based tests will soon be as widespread as "standard" biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information. This review summarizes the techniques available for the isolation and analysis of circulating free DNA and RNA, exosomes, tumor-educated platelets, and circulating tumor cells from the blood of cancer patients, presents the methodological challenges associated with each of these materials, and discusses the clinical applications of liquid biopsy testing in lung cancer.

17.
Pharmacogenomics ; 16(15): 1751-60, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26427522

RESUMO

Significant advances have been made in the analysis of the human genome in the first decades of the 21st century and understanding of tumor biology has matured greatly. The identification of tumor-associated mutations and the pathways involved has led to the development of targeted anticancer therapies. However, the challenge now in using chemotherapy to treat nonsmall-cell lung cancer is to identify more molecular markers predictive of drug sensitivity and determine the optimal drug sequences in order to tailor treatment to each patient. This approach could permit selection of patients who could benefit most from a specific type of chemotherapy by matching their tumor and individual genetic profile. Nevertheless, this potential has been limited so far by reliance on the single biomarker approach, though this is now on the way to being overcome through whole genome studies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Farmacogenética , Estudo de Associação Genômica Ampla , Humanos , Medicina de Precisão
18.
Rev. colomb. cardiol ; 27(3): 193-200, May-June 2020. tab, graf
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1289212

RESUMO

Resumen Objetivo: determinar el efecto de un programa de rehabilitación en los puntajes de ansiedad y depresión de pacientes con enfermedad cardiovascular. Materiales y métodos: se analizó la información de una cohorte retrospectiva de pacientes con enfermedad cardiovascular, admitidos a un programa de rehabilitación cardiaca. La ansiedad y depresión fueron medidas con la escala HADS (Hospital Anxiety and Depression Scale) y se categorizaron según el tratamiento de base recibido (médico o quirúrgico). Se comparó el cambio en los puntajes de ansiedad y depresión al ingreso y al final de la rehabilitación cardiaca mediante la prueba de Wilcoxon para muestras pareadas y la prueba de McNemar para evaluar el cambio de los porcentajes en cada subescala. Resultados: se incluyeron 1.221 pacientes. La mediana de edad fue 61 años, 68,30% eran hombres. Al ingreso, la mediana del puntaje de ansiedad y depresión fue 3, de los cuales 141 pacientes presentaron un trastorno de ansiedad (11,55%) y 67 un trastorno depresivo (5,49%). Al final de la rehabilitación cardiaca se obtuvo una mejoría en los puntajes de ansiedad y depresión tanto en pacientes en tratamiento médico (promedio -1,87 puntos 95% IC -2,14 a -1,60 p<0,01 y -1,46 puntos 95% IC -1,72 a -1,21 p<0,01 respectivamente) como quirúrgico (promedio -1,48 puntos 95% IC -1,78 a -1,18 p<0,01 y -1,83 puntos 95% IC -2,12 a -1,57 p<0,01). Conclusiones: los puntajes de ansiedad y depresión, en pacientes con enfermedad cardiovascular en tratamiento médico o quirúrgico, mejoraron luego de un programa integral de rehabilitación cardíaca.


Abstract Objective: To determine the effects of a rehabilitation program on the anxiety and depression scores of patients with cardiovascular disease. Materials and methods: An analysis was performed on the information collected from a retrospective cohort of patients with cardiovascular disease, admitted to a cardiac rehabilitation program. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS), and were classified according to the baseline treatment (medical or surgical) received. A comparison was made between the anxiety and depression scores on admission and at the end of the cardiac rehabilitation program using Wilcoxon test for paired samples and the McNemar test to evaluate the change in the percentages in each sub-scale. Results: A total of 1,221 patients were included. The median age was 61 years, and 68.3% were males. On admission, the median score was 3 on the anxiety and depression scale, with 141 (11.55%) patients having an anxiety disorder, and 67 (5.49%) with depressive disorder. An improvement was observed in the anxiety and depression scores at the end of the end of the cardiac rehabilitation, both in patients on medical treatment (mean difference minus 1.87 points, 95% CI; -2.14 to -1.60: P<.01, and -1.46 points, 95% CI; -1.72 to -1.21: P<.01, for anxiety and depression, respectively) and on surgical treatment (mean difference -1.48 points, 95% CI; -1.78 to -1.18, P<.01 and -1.83 points, 95% CI -2.12 to -1.57, P<.01, respectively). Conclusions: The anxiety and depression scores in patients with cardiovascular disease on medical or surgical treatment improved after an integrated cardiac rehabilitation program.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Ansiedade , Reabilitação , Transtorno Depressivo , Reabilitação Cardíaca , Ansiedade , Transtornos de Ansiedade , Exercício Físico , Fatores de Risco de Doenças Cardíacas
19.
Transl Lung Cancer Res ; 4(6): 752-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26798584

RESUMO

Cancer treatment as we know it today has dramatically changed over the last couple of decades. It has moved from non-specific treatment to personalized approaches. As oncologist, we now have further understanding of the processes leading to carcinogenesis; this has led to develop new therapeutic options. We have cytotoxic treatments, targeted therapy and in recent years, immunotherapy; the time to "mix and match" has begun.

20.
Cancer Biol Med ; 12(3): 259, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26487971

RESUMO

[This corrects the article on p. 87 in vol. 12, PMID: 26175924.].

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