Cáncer de tiroides en estadios avanzados tratados con inhibidores de tirosina quinasa (SORAFENIB) / Advanced stage thyroid cancer treated with tyrosine kinase inhibitors (SORAFENIB)

OBJETIVO: Este estudio pretende evaluar la sobrevida global en los pacientes con carcinoma diferenciado de tiroides localmente avanzado yodo refractario. MÉTODO: Son 8 casos tratados con inhibidores de tirosina quinasa (Sorafenib) en el período comprendido entre 2014-2017. Las variables estudiadas fueron: Epidemiológicas, laboratorios tiroideos, histología, tratamiento, supervivencia posterior al tratamiento. Se tomó como significativo una P<0,05. RESULTADOS: Edad media entre los pacientes fue 51 años ± 22,1 años, el sexo prevaleciente fue femenino (75 %). El lugar de procedencia más incidente fue Estado Miranda (50 %). Los valores de laboratorio al momento del diagnóstico fueron tiroglobulina (290,2 ± 250,7), la TSH (11,3 ± 13,9) y la antitiroglobulina solo fue positiva en un paciente (87,5 %). La T predominante fue T3 (50 %), la N que prevaleció fue N1B (62 %) y M1 (62,5 %). El estadio predominante fue IVC (50 %). El grupo histológico predominante fue papilar (62,5 %). Se les realizó tiroidectomía total con vaciamiento bilateral al 75 % de los pacientes. Posteriormente recibieron 131I, para los cuales se obtuvieron una dosis media de 227,5 mCi con desviación de estándar: 188,1 mCi. La mayoría recibió radioterapia externa a región cervical (87,50 %). La sobrevida global 3 años posteriores al tratamiento fue 87,5 %. CONCLUSIONES. El control de la enfermedad a largo plazo en estos pacientes avanzados puede obtenerse con Sorafenib. En nuestro estudio evidenciamos que es un fármaco adecuado para controlar la enfermedad en pacientes con cáncer de tiroides yodo refractarios.(AU)

OBJECTIVE: This study aimed evaluates overall survival in patients with locally advanced thyroid iodine refractory differentiated carcinoma. METHOD: 8 cases treated with inhibitors of tyrosine kinase (Sorafenib) in the period 2014-2017. The variables studied were: epidemiological, laboratory thyroid histology, treatment, post-treatment survival. P was taken as meaningful < 0.05. RESULTS: Mean age among patients was 51 years ± 22.1 year, prevailing sex female (75 %). Place of origin more incident was Miranda State (50 %). At the time of the diagnostic laboratory values were thyroglobulin (290.2 ± 250.7), TSH (3 ± 13.9 11) and the single antithyroglobulin was positive in one patient (87.5 %). The predominant T was T3 (50 %), the N that prevailed was N1B (62 %) and M1 (62.5 %). The predominant stadium was IVC (50 %). The predominant histological group was papillary (62.5 %). The predominant stadium was IVC (50 %). The predominant histological group was papillary (62.5 %). He was performed in total thyroidectomy with bilateral clearing to 75 % of patients. Subsequently received 131I, for which an average dose of 227.5 mCi with standard deviation were obtained: 188.1 mCi. Most received radiotherapy external cervical region (87.50 %). Global survival 3 years after treatment was 87.5 %. CONCLUSIONS: The control of disease in long run in these advanced patients can get with Sorafenib. In our study we showed that it is a suitable drug to control the disease in patients with cancer of thyroid iodine refractory. (AU)

In-Lab Upfront Use of Tirofiban May Reduce the Occurrence of No-Reflow During Primary Percutaneous Coronary Intervention. A Pilot Randomized Study / Uso de Tirofibana em Laboratório pode Reduzir Ocorrência de não Reperfusão Durante Intervenção Coronariana Percutânea Primária. Um Estudo Piloto Randomizado

Abstract Background: Despite successful opening of culprit coronary artery, myocardial reperfusion does not always follows primary percutaneous coronary intervention (PPCI). Glycoprotein IIb/IIIa inhibitors are used in the treatment of no-reflow (NR), but their role to prevent it is unproven. Objective: To evaluate the effect of in-lab administration of tirofiban on the incidence of NR in ST-elevation myocardial infarction (STEMI) treated with PPCI. Methods: STEMI patients treated with PPCI were randomized (24 tirofiban and 34 placebo) in this double-blinded study to assess the impact of intravenous tirofiban on the incidence of NR after PPCI according to angiographic and electrocardiographic methods. End-points of the study were: TIMI-epicardial flow grade; myocardial blush grade (MBG); resolution of ST-elevation < 70% (RST < 70%) at 90min and 24h after PPCI. Results: Baseline anthropometric, clinical and angiographic characteristics were balanced between the groups. The occurrence of TIMI flow < 3 was not significantly different between the tirofiban (25%) and placebo (35.3%) groups. MBG ≤ 2 did not occur in the tirofiban group, and was seen in 11.7% of patients in the placebo group (p=0.13). RST < 70% occurred in 41.6% x 55.8% (p=0.42) at 90min and in 29% x 55.9% (p=0.06) at 24h in tirofiban and placebo groups, respectively. Severe NR (RST ≤ 30%) was detected in 0% x 26.5% (p=0.01) at 90 min, and in 4.2% x 23.5% (p=0.06) at 24h in tirofiban and placebo groups, respectively. Conclusion: This pilot study showed a trend toward reduction of NR associated with in-lab upfront use of tirofiban in STEMI patients treated with PPCI and paves the way for a full-scale study testing this hypothesis.

Resumo Fundamento: Mesmo com abertura da artéria coronária culpada bem sucedida, a reperfusão miocárdica nem sempre sucede a intervenção coronariana percutânea primária (ICPP). Inibidores da glicoproteína IIb/IIIa são usados no tratamento do fenômeno de não reperfusão (NR), mas seu papel para preveni-lo não está comprovado. Objetivo: Avaliar o efeito da administração, em laboratório, de tirofibana sobre a incidência de NR em infarto agudo do miocárdio com supra do segmento ST (IAMCSST) tratado com ICPP. Métodos: Pacientes com IAMCSST tratados com ICPP foram randomizados (24 tirofibana e 34 placebo) neste estudo duplo-cego para avaliar o impacto de tirofibana intravenosa sobre a incidência de NR após ICPP de acordo com métodos angiográficos e eletrocardiográfico. Os desfechos do estudo foram: fluxo epicárdico TIMI (grau), grau de fluxo miocárdico (MBG), resolução da elevação do segmento ST < 70% (RST < 70%) aos 90 minutos e 24 horas após ICPP. Resultados: Características antropométricas, clínicas e angiográficas basais eram equilibradas entre os grupos. A ocorrência de fluxo TIMI < 3 não foi significativamente diferente entre os grupos tirofibana (25%) e placebo (35,3%). MBG ≤ 2 não ocorreu no grupo tirofibana, e foi detectado em 11,7% dos pacientes do grupo placebo (p=0,13). RST < 70% ocorreu em 41,6% x 55,8% (p=0.42) aos 90 minutos, e em 29% x 55,9% (p=0,06) em 24 horas nos grupos tirofibana e placebo, respectivamente. NR grave (RST ≤ 30%) ocorreu em 0% x 26,5% (p=0,01) aos 90 minutos, e em 4,2% x 23,5% (p=0,06) em 24 horas nos grupos tirofibana e placebo, respectivamente. Conclusão: Este estudo piloto mostrou uma tendência de redução de NR associada ao uso, em laboratório, de tirofibana em pacientes com IAMCSST tratados com ICPP, e abre caminho para um estudo em escala real que teste essa hipótese.

Meta-tyrosine: A powerful anti-metastatic factor with undetectable toxic-side effects

Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. While former studies have indicated that T-cell dependent processes mediate CR in hosts bearing immunogenic small tumors, the most universal manifestation of CR induced by immunogenic and non-immunogenic large tumors had been associated with an antitumor serum factor that remained an enigma for many years. In a recent paper, we identified that elusive factor(s) as an equi-molar mixture of meta-tyrosine and ortho-tyrosine, two isomers of tyrosine that are not present in normal proteins and that proved to be responsible for 90% and 10%, respectively, of the total serum anti-tumor activity. In this work, we have extended our previous findings demonstrating that a periodic intravenous administration of meta-tyrosine induced a dramatic reduction of lung and hepatic metastases generated in mice bearing two different metastatic murine tumors and decreased the rate of death from 100% up to 25% in tumor-excised mice that already exhibited established metastases at the time of surgery. These anti-metastatic effects were achieved even at very low concentrations and without displaying any detectable toxic-side effects, suggesting that the use of meta-tyrosine may help to develop new and less harmful means of managing malignant diseases, especially those aimed to control the growth of metastases that is the most serious problem in cancer pathology.

La resistencia concomitante antitumoral (RC) es el fenómeno según el cual un individuo portador de tumor inhibe el crecimiento de implantes tumorales secundarios y metástasis. Si bien desde hace tiempo se sabe que la RC inducida por tumores inmunogénicos de pequeño tamaño es generada por mecanismos inmunológicos dependientes de células T, por otro lado, la manifestación más universal de la RC, generada tanto por tumores inmunogénicos como no-inmunogénicos de gran tamaño, había sido asociada con un (unos) factor sérico antitumoral cuya naturaleza permaneció elusiva por años. En un trabajo reciente, nuestro grupo de trabajo identificó este factor como la mezcla equi-molar de meta-tirosina y orto-tirosina, dos isómeros de tirosina que no están presentes en proteínas normales y que demostraron ser responsables del 90% y 10%, respectivamente, de la actividad antitumoral total del suero. En este trabajo, continuamos nuestras investigaciones demostrando que la administración periódica de meta-tirosina reducía drásticamente el número de metástasis pulmonares y hepáticas en ratones portadores de dos tumores murinos altamente metastásicos y disminuía dramáticamente la mortandad (de 100% a 25%) de ratones con metástasis ya establecidas al momento de la extirpación quirúrgica del tumor. Estos efectos anti-metastásicos se lograron aun con muy bajas concentraciones de meta-tirosina y sin efectos tóxicos perceptibles, lo que sugiere que su uso puede ayudar a diseñar nuevas y menos nocivas estrategias para el tratamiento del cáncer, especialmente aquellas destinadas a controlar el crecimiento metastásico, que es el problema más grave en la enfermedad oncológica.

Rescue Treatment with Intra-arterial Tirofiban Infusion and Emergent Carotid Stenting

Rapid arterial rethrombosis is associated with high-grade residual stenosis and usually occurs at the site of the initial occlusion, resulting in reocclusion of the recanalized artery. Platelets may play an active role in such rethrombosis after thrombolytic-induced clot lysis. Given that glycoprotein IIb/IIIa receptor blockers, like tirofiban, prevent thrombus formation by inhibiting the final common pathway of platelet aggregation, they may be helpful for treating rethrombosis after thrombolysis. A 64-year-old man presented with an acute ischemic stroke due to internal carotid artery (ICA) occlusion. The ICA was recanalized by intravenous thrombolysis but reoccluded shortly after recanalization. The reoccluded ICA was successfully recanalized using intra-arterial tirofiban. A carotid stent was subsequently inserted to relieve severe stenosis and to prevent recurrent stroke. Here, we report a case of rescue treatment of a successfully recanalized ICA by intra- arterial tirofiban. We suggest that rescue use of intra-arterial tirofiban may be effective and safe, especially in hemorrhage prone situations, due to the relatively lower dose of tirofiban compared with intravenous doses.

Endogenous alkaloids in the brain of rats loaded with tyrosine/tryptophan & in the serum of patients of neurodegenerative & psychiatric disorders.

Since binding sites for morphine, nicotine and strychnine exist in the brain, it is possible that they may have some role in neuronal function. The presence/variation in the levels of these alkaloids in the brain of rats fed tryptophan and tyrosine, and in the serum of patients with some neurodegenerative and psychiatric disorders were studied. Brain of rats loaded with tyrosine (500 mg/kg b wt X 14 days) showed increased amounts of morphine, while that from animals loaded with tryptophan (in the same dose) showed presence of strychnine and increased amounts of nicotine. Strychnine is being reported in mammalian brain for the first time. Serum of patients with epilepsy, Parkinson's disease (PD) and manic depressive psychosis (MDP) was also examined for the presence of these alkaloids. Serum of control subjects did not show the presence of any of these alkaloids, while that of all 3 patients groups contained strychnine. Morphine was present only in the serum of patients of MDP. Nicotine was present in trace amounts in the serum of all these patients. Presence of these alkaloids in the serum of patients of neurodegenerative and psychiatric disorders is being reported for the first time, to the best of our knowledge.

Alteraçöes enzimáticas no hipotirodismo primário: características bioquímicas antes e após a terapêutica com doses incrementais de L-tiroxina / Enzymatic changes in primary hypothyroidism before and after treatment with increased doses of L-thyroxine

O objetivo deste estudo foi analisar as alteraçöes enzimáticas no hipotiroidismo primário antes e após a terapêutica com tiroxina. Para tal, estudamos 12 pacientes com hipotiroidismo primário, nos quais medimos os valores séricos de CPK, CK-MB, DHL, isoenzimas de DHL, TGO, TSH, T4 e T3 antes do tratamento, 15 e 45 dias após a terapêutica com tiroxina. A CPK basal apresentava-se com valores elevados na maioria dos pacientes; (9/12) e significantemente aumentada em relaçäo aos controles normais (p < 0,05); após 15 dias de terapêutica os valores ainda permaneciam aumentados (p < 0,05) e no 45§ dia de terapêutica estavam dentro da normalidade em todos os pacientes;. A contribuiçäo de fraçäo cardíaca (CK-MB) foi sempre mínima e dentro dos valores normais. A DHL total basal apresentava-se com valores aumentados em 5 dos 12 pacientes e significantemente aumentada em relaçäo aos controles normais (p < 0,05); após 15 dias de terapêutica os valores ainda permaneciam elevados (p < 0,05) e no 45§ dia estavam dentro da normalidade em todos os pacientes; a avaliaçäo isoenzimática revelou elevaçäo da fraçäo 5. A TGO basal apresentava-se com valores aumentados na maioria dos pacientes; (7/12) e significantemente aumentada em relaçäo aos controles normais (p < 0,05); após 15 dias de terapêutica os valores ainda permaneciam elevados (p < 0,05) e no 45§ dia estavam dentro da normalidade em todos os pacientes;. O TSH basal apresentava-se com valores aumentados em todos os pacientes; e significantemente mais elevados comparativamente a controles normais (p < 0,05) mesmo após 15 e 45 dias de terapêutica (p < 0,05). Os dados obtidos demonstram: 1) pacientes com hipotiroidismo primário evidenciam anormalidades enzimáticas (83,3% possuem CPK elevada, 41,7% apresentam DHL elevada e 58,3% mostram TGO elevada); 2) a elevaçäo enzimática é provavelmente decorrente de alteraçöes musculares; 3) as alteraçöes enzimáticas retornam à normalidade com a terapêutica à base de tiroxina precocemente em relaçäo ao TSH