ABSTRACT Objective: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. Materials and methods: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). Results: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). Conclusions: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

SUMMARY Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.

The therapeutic approach and the follow-up of patients with differentiated thyroid cancer (DTC) is currently individualised according to the risk of recurrence, with a lower tendency to perform remnant ablation (RA) in patients with low risk of recurrence. While response to therapy assessment has been validated for DTC patients treated by total thyroidectomy (TT) and RA, it has not been widely confirmed in patients treated with TT without RA. The aims of this study were to describe the characteristics of the population of patients treated with TT without RA, and to validate the response to therapy. The study included 88 patients followed-up for at least 12 months after surgery. In the entire cohort, 87.9% were female and the mean age was 47.5 years old. Based on the Argentine Intersociety Consensus, 97.7% and 2.3% were classified as low risk and intermediate risk of recurrence, respectively. Patients had an initial excellent response to treatment in 73% of cases, with a disease-free status at the end of follow-up of 85.5%. A minority of patients (1%) presented with an initial structural incomplete response, which was similar at the end of follow-up (1%). On the other hand, 26% of the patients had an initial indeterminate response, although only 13.5% remained with this response at the end of follow-up. These results validate the responses to treatment in DTC patients treated with TT without RA as an effective tool for the dynamic risk stratification. Patients appropriately selected who did not receive RA have an excellent outcome, with a low frequency of structural incomplete response, even lower than that observed in low risk ablated patients.

En la actualidad, el enfoque terapéutico y el seguimiento de los pacientes con carcinoma diferenciado de tiroides (CDT) es individualizado de acuerdo con el riesgo de recurrencia de la enfermedad, con una menor tendencia a ablacionar a pacientes de bajo riesgo de recurrencia. Por otro lado, la evaluación de las respuestas al tratamiento se validó en pacientes tratados con tiroidectomía total (TT) y ablación con radioyodo (RAI), pero son escasos los estudios en pacientes no ablacionados. Los objetivos de este estudio fueron describir las características de una población de pacientes con CDT no ablacionados y validar las respuestas al tratamiento durante el seguimiento. Se incluyó a 88 pacientes con un seguimiento mínimo de 12 meses. El 87,6% eran mujeres y la edad promedio en el momento del diagnóstico fue de 47,5 años. Basados en el Consenso Intersocietario Argentino, el 97,7% de la cohorte fue clasificada como de bajo riesgo y el 2,3% como de riesgo intermedio de recurrencia. Los pacientes presentaron una respuesta inicial excelente en el 73% de los casos, con un estado sin evidencia de enfermedad al final del seguimiento en el 85,5%. Una minoría de los pacientes (1%) presentó una respuesta inicial estructural incompleta, la cual fue similar al final del seguimiento (1%). Por otro lado, el 26% de los pacientes presentó una respuesta inicial indeterminada, aunque solo el 13,5% permaneció con esta respuesta al final del seguimiento. Nuestros datos validan las respuestas al tratamiento en pacientes con CDT que recibieron TT no ablacionados como una herramienta efectiva para la estratificación del riesgo dinámico. Los pacientes apropiadamente seleccionados tratados sin RAI tienen un excelente pronóstico, con una baja frecuencia de respuesta estructural incompleta en el seguimiento, inclusive menor que la de los pacientes de bajo riesgo ablacionados.

The advent of multikinase inhibitors therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The ANMAT (the Argentinian regulatory health agency) has currently approved sorafenib for patients with radioiodine resistant differentiated thyroid carcinoma, and vandetanib for patients with medullary thyroid carcinoma (progressive and/or symptomatic disease). It has been demonstrated by phase III clinical trials that these drugs improve progression free survival in this group of patients. Although they have a precise indication, an interdisciplinary team in close contact with a committed patient, are required for their effective management. The adverse events of these drugs are common, but many of them may ameliorate over time, and most of them are manageable, even without the need for dose reduction or drug withdrawal. Knowledge of the correct management of the adverse events is a fundamental tool for the medical team and for the patient to prevent or minimise them, to avoid serious complications and to obtain better patient compliance. The primary objective of this article is to provide a guideline for the diagnosis and treatment of the adverse events produced by the multikinase inhibitors, and to present the initiative of the Hospital de Clinicas in order to implement these guidelines.

El advenimiento de la terapia con inhibidores multicinasas (IMK) representó un cambio radical en el tratamiento de pacientes con carcinoma avanzado de tiroides. Hasta la fecha, 2 fármacos se encuentran aprobados por la Asociación Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) en Argentina: sorafenib, para pacientes con carcinoma diferenciado de tiroides radiorresistente, y vandetanib, para aquellos con carcinoma medular de tiroides (enfermedad progresiva y/o sintomática). Los estudios de fase III han demostrado que estos fármacos aumentan significativamente la supervivencia libre de progresión en este grupo de pacientes. Si bien tienen una indicación precisa, su manejo requiere de un equipo multidisciplinario en contacto estrecho con un paciente involucrado en su tratamiento. Los efectos adversos de sorafenib y vandetanib son frecuentes, sin embargo, muchos de ellos disminuyen con el tiempo y la mayoría puede manejarse a menudo sin disminuir la dosis ni suspender el fármaco. El conocimiento del correcto manejo de los efectos adversos por parte del equipo tratante constituye una herramienta fundamental para poder educar al paciente y, consecuentemente, poder prevenirlos o minimizarlos, y de esta manera evitar complicaciones severas. El objetivo de esta publicación es brindar una guía para el diagnóstico y tratamiento de los efectos adversos de estos IMK y, por otro lado, presentar la iniciativa del Hospital de Clínicas de la Universidad de Buenos Aires en cuanto a la implementación de la misma.

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

Caesalpinia peltophoroides is a domesticated tree found in Brazil. It was necessary to develop an analytical method to determine the content of total polyphenols (TP) in this herbal drug. The pre-analytical method was standardized for analysis time, wavelength, and the best standard to use. The optimum conditions were: pyrogallol, 760 nm, and 30 min respectively. Under these conditions, validation by UV/Vis spectrophotometry proved to be reliable for TP of the crude extract and semipurified fractions from C. peltophoroides. Standardization is required for every herbal drug, and this method proved to be linear, precise, accurate, reproducible, robust, and easy to perform.

Os estudantes de Medicina compõem um grupo susceptível aos transtornos do sono, em razão da carga curricular em horário integral, das atividades extracurriculares e da forte pressão e estresse, com exigência de alto rendimento e tempo demandado em estudos. O objetivo deste trabalho foi avaliar os hábitos do sono dos estudantes da graduação e residentes da Faculdade de Medicina da Universidade Federal de Goiás, a fim de identificar os principais fatores que afetam a qualidade do sono. Foram analisados 276 estudantes, sendo 234 (84,7%) acadêmicos e 42 (18,2%) residentes. Aplicou-se o questionário Índice de Qualidade do sono de Pittsburg (PSQI) e a escala de sonolência de Epworth. A análise dos questionários revelou associação estatisticamente significante entre sonolência e qualidade do sono (RR:1,108; IC 95% 1,0047 - 1,2240). O trabalho demonstrou que estudantes com sonolência diurna excessiva apresentam pior qualidade de sono; e uma variação significativa da prevalência da sonolência diurna excessiva e da qualidade ruim do sono entre as amostras de primeiro ano de graduação e residentes.

As a group, medical students are particularly susceptible to sleep disorders, due to their full-time course load, extracurricular activities, and heavy pressure and stress, with the demand for high yield and extensive study time. The aim of this study was to evaluate the sleeping habits of medical students and residents at the School of Medicine, Federal University in Goiás, in order to identify the principal factors that affect quality of sleep. The study analyzed a sample of 276 individuals, including 234 (84.7%) undergraduate medical students and 42 (18.2%) residents. The study used the questionnaire for the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Analysis of the questionnaires showed a statistically significant association between sleepiness and quality of sleep (RR: 1.108; 95%CI 1.0047 - 1.2240). The study showed that students with excessive daytime sleepiness present worse quality of sleep, and that there was a significant variation in the prevalence of excessive daytime sleepiness and poor quality of sleep when comparing first year undergraduates and residents.

OBJETIVO: Descrever as características e a evolução de lactantes com bronquiolite aguda submetidos à ventilação mecânica. MÉTODOS: Estudo retrospectivo desenvolvido entre março 2004 e setembro 2006 (três invernos consecutivos), recrutando todos os lactantes (menos de 12 meses de idade) com diagnóstico de bronquiolite viral aguda e submetidos à ventilação mecânica em uma unidade de terapia intensiva, brasileira, ligada a uma universidade. Os parâmetros de ventilação mecânica adotados no 1°, 2° 3° e 7° dia e antes da extubação foram avaliados, assim como a evolução (taxa de mortalidade, presença da síndrome de desconforto respiratório agudo) e prevalência de complicações. Os grupos foram comparados usando o teste t de Student, o teste U de Mann-Whitney e o teste Qui-Quadrado. RESULTADOS: Foram incluídos 59 lactantes (3,8 ± 2,7 meses de idade, 59% de sexo masculino) com 9,0 ± 9,4 dias em ventilação mecânica. Antes da ventilação mecânica, ventilação não-invasiva foi instituída em 71% dos lactantes. Foi observada anemia em 78% da amostra. Em 51 lactantes (86,5%), o padrão obstrutivo de vias aéreas inferiores foi mantido até extubação intratraqueal, com mortalidade nula e baixa prevalência de pneumotórax (7,8%). A síndrome de desconforto respiratório agudo, ocorreu em 8 lactantes (13,5%) com mortalidade mais elevada e alta prevalência de pneumotórax (62,5%). CONCLUSÕES: O declínio na mortalidade em crianças com bronquiolite viral aguda tem sido observado mesmo em regiões não desenvolvidas, com altas taxas de anemia e partos prematuros. A baixa mortalidade está associada à manutenção o padrão obstrutivo de vias aéreas inferiores durante o tempo em ventilação mecânica. O desenvolvimento da síndrome de desconforto respiratório agudo está associado a uma mortalidade mais elevada e maior porcentagem de complicações representando o desafia atual para o tratamento de crianças com bronquiolite viral aguda.

OBJECTIVE: To describe the characteristics and the outcome of infants with acute viral bronchiolitis submitted to mechanical ventilation. METHODS: We performed a retrospective study enrolling all infants (less than 12 months old) admitted with the diagnosis of acute viral bronchiolitis and submitted to mechanical ventilation in an university affiliated Brazilian pediatric intensive care unit between March, 2004 and September, 2006 (3 consecutives winters). The mechanical ventilation parameters' employed on 1st, 2nd, 3rd, 7th day and before extubation were evaluated as well as the evolution (mortality rate, presence of acute respiratory distress syndrome and the prevalence of complications). The groups were compared using the Student t test, the Mann-Whitney U test and the Chi-square test. RESULTS: Fifty-nine infants were included (3.8 ± 2.7 months old, 59% male), with 9.0 ± 9.4 days on mechanical ventilation. Prior mechanical ventilation, non invasive ventilation was instituted in 71% of children. Anemia was observed in 78% of the sample. In 51 infants (86.5%) the lower airway obstructive pattern was maintained up to tracheal extubation with a nil mortality and low prevalence of pneumothorax (7.8%). Acute respiratory distress syndrome occurred in 8 infants (13.5%), with higher mortality and a higher prevalence of pneumothorax (62.5%). CONCLUSIONS: The declining mortality in acute viral bronchiolitis is observed even in non developed regions, involving children with high rates of anemia and premature labor. The low mortality is associated with the maintenance of the lower airway obstructive pattern during the period on mechanical ventilation. The development of acute respiratory distress syndrome is associated with increased mortality and higher prevalence of complications, representing the actual challenge in the management of children with severe acute viral bronchiolitis.

OBJETIVO: Avaliar os modos de morte e fatores associados à limitação de suporte de vida em três unidades de terapia intensiva pediátrica do sul do Brasil. MÉTODO: Estudo transversal e retrospectivo em que foram revisados todos os óbitos ocorridos em 2002 em três unidades de terapia intensiva pediátrica de referência de Porto Alegre por uma equipe de pesquisadores treinados para esse fim. Foram avaliadas as características gerais, o modo de morte (ressuscitação cardiopulmonar, morte encefálica, ordem de não reanimar, não oferta e retirada de suporte vital - esses três últimos agrupados em limitação de suporte de vida), o tempo de internação - hospitalar e na unidade de terapia intensiva pediátrica -, o plano de final de vida e a participação da família nessa decisão. Para as comparações, foram utilizados o teste t de Student, Mann Whitney, qui-quadrado, odds ratio e análise multivariada. RESULTADOS: Aproximadamente 53,3% dos óbitos receberam ressuscitação cardiopulmonar. A incidência de limitação de suporte de vida foi de 36,1%, havendo diferença significativa (p = 0,014) entre os hospitais (25 versus 54,3 e 45,5%). A forma de limitação de suporte de vida mais freqüente foi "ordem de não reanimar" (70%). Observou-se associação entre limitação de suporte de vida com presença de doença crônica (odds ratio = 8,2; IC95% = 3,2-21,3) e tempo de internação na unidade de terapia intensiva pediátrica > 24h (odds ratio = 4,4; IC95% = 1,6-11,8). A participação da família e dos comitês de ética no plano de final de vida foi inferior a 10%. CONCLUSÕES: A ressuscitação cardiopulmonar ainda é oferecida em uma freqüência maior do que a descrita nos países do hemisfério norte, enquanto que a limitação de suporte vital é realizada preferentemente através da ordem de não reanimar. Esses achados e a pequena participação da família refletem dificuldades em relação às decisões de final de vida enfrentadas por intensivistas do sul do Brasil.

OBJECTIVES: To describe causes of death and factors involved in the decision-making process related to life support limitation at three university-affiliated pediatric intensive care units in the south of Brazil. METHODS: A retrospective study was conducted, based on a review of the medical records of all deaths occurring during 2002 at three pediatric intensive care units in Porto Alegre. Three previously trained pediatric fellows from each service performed the study. Data were assessed relating to general case characteristics, causes of death (failed cardiopulmonary resuscitation, brain death, do-not-resuscitate orders, withholding or withdrawing life-sustaining treatment - the last three modes were classified as the life support limitation group), length of stay in hospital, end-of-life plans and the participation of patients' families and Ethics Committees. The Student t test, Mann Whitney, chi-square, odds ratio and multivariate analyses were used for comparisons. RESULTS: Close to 53.3% of fatal cases had received full cardiopulmonary resuscitation. The incidence of life support limitation was 36%, with statistical differences (p = 0.014) between the three hospitals (25 versus 54.3 and 45.5%, respectively). The most frequent form of life support limitation was a do-not-resuscitate order (70%). Life support limitation was associated with the presence of chronic disease (odds ratio = 8.2; 95%CI 3.2-21.3) and length stay in the pediatric intensive care unit (odds ratio = 4.4; 95%CI 1.6-11.8). The rate of involvement of families and Ethics Committees in the decision-making process was lesser than 10%. CONCLUSIONS: Cardiopulmonary resuscitation is offered more frequently than is observed in northern countries. In contrast, life support limitation is offered through do-not-resuscitate orders. These findings and the low participation of the families in the decision-making process reflect the difficulties to be overcome by those professionals who are responsible for handling critically ill children in southern Brazil.