Prise en charge du cancer du col utérin métastatique au CHU de Treichville et résultas/ / Management of metastatic cervical cancer at the University Hospital of Treichville and results

la prise en charge du cancer col métastatique s'est enrichie depuis 2017 par la disponibilité des thérapies ciblées dans notre pays. Cette étude avait pour objectifs de déterminer les caractéristiques épidémiologiques, cliniques et thérapeutiques des patientes prises en charge pour cancer du col métastatique dans notre structure. Methodes. il s'agit d'une étude rétrospective à visé descriptive menée dans les services de gynécologie et d'oncologie du CHUT, du janvier 2018 ­ octobre 2021. Elle a concerné les dossiers de patientes traitées pour un cancer du col de l'utérus métastatique confi rmé. Ont été inclus les dossiers des patientes qui ont reçu au moins 06 cures de chimiothérapie associées ou non à la thérapie ciblée, et dont la dernière cure a été réalisée 24 mois avant la fi n de l'étude. Resultats. Nous avons colligé 47 dossiers dont les patientes avaient un âge moyen de 54 ans. Elles avaient toutes déjà accouché, et étaient sans activités dans 57% des cas. La tumeur initiale était un carcinome épidermoïde dans la majorité des cas (87%). Les sites métastatiques les plus fréquents étaient lespoumons (39%), le foie (26%), les os (15%). Elles ont toutes bénéfi cié de la combinaison PaclitaxelCisplatine ­Bévacizumab comme traitement spécifi que. La survie globale a été de 52 % à 24 mois, et était meilleur chez les patientes qui ont reçu le Bévacizumab dans leur traitement.

Resultados terapéuticos de la papilomatosis respiratoria recurrente en otorrinolaringología Hospital de Clínicas periodo 2005 a 2020 / Therapeutic results of recurrent respiratory papillomatosis in otorhinolaryngology Hospital de Clinicas period 2005 to 2020

Introducción: La papilomatosis respiratoria recurrente es el crecimiento de lesiones papilomatosas en el tracto aerodigestivo causada por el virus del papiloma humano, aparece más entre los 3 y 6 años (juvenil) y entre la tercera y quinta décadas (adulta). Los síntomas suelen ser disfonía y dificultad respiratoria. La terapéutica consiste en la resección de lesiones y terapia adyuvante (bevacizumab e interferón). Su curso es variable, tiende a recidivar y maligniza en 3-7%, más en adultos. Objetivos: Describir resultados terapéuticos de la papilomatosis respiratoria recurrente en nuestro servicio. Materiales y métodos: Estudio observacional, descriptivo con asociación cruzada, transversal, retrospectivo, muestreo no probabilístico de casos consecutivos, de pacientes con papilomatosis respiratoria recurrente operados en la Cátedra y Servicio Otorrinolaringología del Hospital de Clínicas en el periodo 2005-2020. Resultados: Se estudiaron 40 pacientes, 65% hombres y 35% mujeres; 35% adultos y 65% juveniles. La media de edad fue 16,05±18,042 años; en los casos juveniles fue 4,69±2,908 años, en los adultos 37,14±14,94 años. Se observaron alteraciones de la voz en el 100% y de la mecánica respiratoria en el 72,5%. Se contabilizaron 119 procedimientos, en 11 pacientes se realizó solamente resección, 29 con adyuvancia, de estos 22,5% recibieron bevacizumab y 50% interferón. No hubo diferencia significativa en la media de tiempo sin lesiones entre jóvenes y adultos (p>0,05), pero si según la terapéutica con tendencia favorable con la adyuvancia, sobre todo con bevacizumab. Se constató displasia en 10% y malignización en 2,5%. La afectación fue: glotis 100% (cuerda vocal derecha 92,5%, izquierda 82,5%, ambas 77,5%, comisura anterior 62,5%), supraglotis 20% y subglotis 10%. El promedio de número de áreas afectas fue 3,34±1,274, hubo una diferencia significativa (p<0,05) entre los casos adultos (2,071±0,379) y juveniles (3,846±1,015) constatándose mayor afectación en este último. Conclusión: La mayor parte fueron casos juveniles masculinos. Las zonas más afectas fueron la glotis, sobre todo cuerdas vocales. En jóvenes se vio mayor número de regiones afectas. Todos presentaban disfonía o afonía, seguido por dificultad respiratoria. Las terapéuticas fueron resección quirúrgica sola o asociada a adyuvancia (bevacizumab o Interferón). El tiempo de recurrencia fue mayor al emplear adyuvancia terapéutica con tendencia favorable hacia el bevacizumab. La malignización ocurrió en un caso.

Introduction: Recurrent respiratory papillomatosis is the growth of papillomatous lesions in the aerodigestive tract caused by human papillomavirus, appears more between the ages of 3 and 6 years (juvenile) and between the third and fifth decades (adult). Symptoms are usually dysphonia and respiratory distress. The therapy consists of resection of lesions and adjuvant therapy (bevacizumab and interferon). Its course is variable, it tends to recur and malignancy occurs in 3-7%, more in adults. Objectives: To describe therapeutic results of recurrent respiratory papillomatosis in our service. Materials and methods: Observational, descriptive, cross-sectional, cross-sectional, retrospective, retrospective, non-probabilistic sampling of consecutive cases, of patients with recurrent respiratory papillomatosis operated in the Otorhinolaryngology Department of the Hospital de Clínicas in the period 2005-2020. Results: We studied 40 patients, 65% male and 35% female; 35% adults and 65% juveniles. Mean age was 16.05±18.042 years. In juvenile cases the mean age was 4.69±2.908 years, in adults 37.14±14.94 years. Voice alterations were observed in 100% and respiratory mechanics in 72.5%. There were 119 procedures, 11 laryngeal microsurgery alone, 29 associated with adjuvant, of these 22.5% received bevacizumab and 50% interferon. There was no significant difference in the mean time without lesions between young people and adults (p>0.05), but there was a favorable trend with adjuvant therapy, especially with bevacizumab. Dysplasia was found in 10% and malignization in 2.5%. The involvement was: glottis 100% (right vocal cord 92.5%, left 82.5%, both 77.5%, anterior commissure 62.5%), supraglottis 20% and subglottis 10%. The average number of affected areas was 3.34±1.274, there was a significant difference (p<0.05) between adult (2.071±0.379) and juvenile (3.846±1.015) cases, with greater involvement in the latter. Conclusion: Most of the cases were juvenile male cases. The most affected areas were the glottis, especially vocal cords. A greater number of affected regions were seen in young people. All presented dysphonia or aphonia, followed by respiratory distress. Therapeutics were surgical resection alone or associated with adjuvant therapy (bevacizumab or interferon). The time to recurrence was longer when adjuvant therapy was used, with a favorable trend towards bevacizumab. Malignization occurred in one case.

Protocolo Clínico e Diretrizes Terapêuticas da Degeneração Macular Relacionada à Idade (forma neovascular) / Clinical Protocol and Therapeutic Guidelines of macular degeneration related to age (neovascular form)

CONTEXTO: Os PCDT são documentos que visam garantir o melhor cuidado de saúde diante do contexto brasileiro e dos recursos disponíveis no SUS. Podem ser utilizados como materiais educativos aos profissionais de saúde, auxílio administrativo aos gestores, regulamentação da conduta assistencial perante o Poder Judiciário e explicitação de direitos aos usuários do SUS. Os PCDT são os documentos oficiais do SUS que estabelecem critérios para o diagnóstico de uma doença ou agravo à saúde; tratamento preconizado, com os medicamentos e demais produtos apropriados, quando couber; posologias recomendadas; mecanismos de controle clínico; e acompanhamento e verificação dos resultados terapêuticos a serem seguidos pelos gestores do SUS. Os PCDT devem incluir recomendações de condutas, medicamentos ou produtos para as diferentes fases evolutivas da doença ou do agravo à saúde de que se tratam, bem como aqueles indicados em casos de perda de eficácia e de surgimento de intolerância ou reação adversa relevante,

Terapia fotodinâmica com verteporfina associada à injeção intravítrea de antifator de crescimento endotelial vascular para tratamento de hemangioma circunscrito de coroide / Photodynamic therapy with verteporfin associated with intravitreal injection of vascular endothelial growth factor for the treatment of circumscribed choroidal hemangioma

RESUMO O hemangioma de coroide é um tumor vascular benigno, de coloração vermelho-alaranjada, bem delimitado, caracterizado por uma placa elevada. É um tumor raro, com prevalência de um caso a cada 40 tumores de coroide. O diagnóstico pode ser feito por meio da clínica associada à avaliação biomicroscópica e a exames complementares para diferenciação de outros tumores. O tratamento pode ser expectante nos casos assintomáticos. Para os casos sintomáticos ou com presença de fluido sub-retiniano, existem diversas terapias. O objetivo deste estudo foi relatar um caso de hemangioma circunscrito de coroide submetido a tratamento combinado de terapia fotodinâmica com verteporfina e injeção intravítrea de antiangiogênico (bevacizumabe). A decisão de tratar um hemangioma de coroide deve ser individualizada com base nos sintomas, na perda visual e em qualquer potencial de sua recuperação. O exame oftalmológico completo é necessário, mesmo em casos assintomáticos, para rastreamento precoce de doenças oculares.

ABSTRACT Choroid hemangioma is a benign, well-delimited orange-red, vascular tumor characterized by an elevated plaque. It is a rare tumor with a prevalence of one case in every 40 choroidal tumors. It can be diagnosed by the clinic associated with biomicroscopic evaluation and complementary tests to differentiate from other tumors. Treatment can be expectant in asymptomatic cases. For symptomatic cases or those with the presence of subretinal fluid, there are several therapies. The objective of this study was to report a case of circumscribed choroidal hemangioma submitted to combined treatment of photodynamic therapy with verteporfin and intravitreal injection of an antiangiogenic agent (bevacizumab). The decision to treat choroidal hemangioma must be individualized based on symptoms, visual loss, and any potential for recovery. A complete eye examination is necessary, even in asymptomatic cases, for early screening for eye diseases.

Terapias sistémicas en carcinoma hepatocelular: secuencia de tratamientos / Systemic therapies in hepatocellular carcinoma: sequencing of treatment

El carcinoma hepatocelular (CHC) es una de las principales causas de morbilidad y mortalidad relacionada con el cáncer en todo el mundo. La mayoría de los casos ocurren en un contexto de cirrosis o hepatitis crónica. Los pacientes con CHC avanzado no disponían de terapias efectivas hasta el 2008, cuando el sorafenib, un inhibidor de la tirosina quinasa multi-target, demostró un beneficio en comparación con el placebo, en términos de supervivencia y tiempo a progresión de la enfermedad. Desde el 2016, diferentes tratamientos de primera y segunda línea con mecanismos de acción similares (lenvatinib, regorafenib, cabozantinib, ramucirumab) demostraron eficacia. Sin embargo, la investigación de fármacos que inhiben otras vías tumorales seguía siendo de máxima prioridad y los inhibidores de puntos de control inmunitario (ICI) mostraron resultados prometedores en el ámbito clínico para el tratamiento del CHC, revolucionando el manejo en estos pacientes. Recientemente, el anticuerpo contra la proteína de muerte programada-1 (PD-1), atezolizumab combinado con bevacizumab, demostró superioridad sobre el sorafenib en un ensayo clínico aleatorizado de fase III, convirtiéndose en la terapia de elección en primera línea. Actualmente están emergiendo resultados de múltiples estudios de fase III, que continuarán modificando el tratamiento del CHC. En este artículo se revisa la evolución y los cambios recientes de las terapias sistémicas para CHC, mostrando la secuencia actual de estos tratamientos, una vez iniciados.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Most cases occur in the context of cirrhosis or chronic liver inflammation. Patients with advanced HCC had no effective therapies until 2008, when sorafenib, a multi-target tyrosine kinase inhibitor, showed beneficial results when compared to placebo in terms of survival and time to progression. Since 2016, different first and second line treatments with similar mechanisms of action (lenvatinib, regorafenib, cabozantinib, ramucirumab) have shown efficacy. However, researchstudies with drugs that inhibit other tumor pathways remained a top priority, and immune checkpoint inhibitors (ICIs) showed promising results in the clinical setting of HCC management. Recently, antibodies against the programmed death protein-1 (PD-1), atezolizumab combined with bevacizumab, have shown superiority over sorafenib in a randomized phase III clinical trial, becoming the first-line therapy of choice. Results from multiple phase III studies are currently emerging, which will continue to modify HCC treatment. This article reviews recent developments and changes in systemic therapies for HCC, showing the current sequencing of these treatments once they begin.

Protocolo assistencial de injeções intravítreas do HCPA: edema macular diabético / HCPA's patient care protocol for intravitreal injections: diabetic macular edema

RESUMO: O edema macular diabético é uma das principais causas de baixa visual no mundo e a indicação mais frequente de injeções intravítreas no Hospital de Clínicas de Porto Alegre. O tratamento com injeção intra-vítrea de medicamentos anti-vascular endothelial growth factor, incluindo o bevacizumaberevolucionou o desfecho visual destes pacientes às custas de múltiplas aplicações mensais. Assim como em outros centros, discrepâncias entre condutas da equipe assistencial e dificuldades logísticas acabam comprometendo a efetividade do tratamento. Portanto, desenvolvemos um protocolo de tratamento para a doença embasado na literatura, estabelecendo critérios de inclusão, exclusão, regime de tratamento e seguimento do paciente. Com isto, esperamos otimizar a efetividade e assistência do paciente com edema macular diabético.

ABSTRACT: Diabetic macular edema is one of the leading causes of visual impairment worldwide and the most common indication for intravitreal injections at the Hospital de Clínicas de Porto Alegre. Treatment with intravitreal injection of anti-vascular endothelial growth factor drugs, including bevacizumab, has revolutionized patient outcome at the expense of multiple monthly injections. As in other hospitals, discrepancies in health team conduct and logistical difficulties compromise treatment effectiveness. Therefore, we developed a literature-based treatment protocol for diabetic macular edema, in which we established criteria for patient inclusion and exclusion, treatment regimen, and patient follow-up. We expect the treatment protocol to optimize patient care effectiveness in diabetic macular edema.

Expert Consensus on the Treatment of Antiangiogenic Agents for Radiation Brain Necrosis / 中国肺癌杂志

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Paraparesis in a young adult: A case report on Neurofibromatosis-2

Background@#Neurofibromatosis-2 (NF2) is a rare neurocutaneous syndrome that typically presents with hearing loss, tinnitus, or weakness associated with few subcutaneous nodules. In contrast to neurofibromatosis-1 (NF1), NF2 presents clinically with more central lesions rather than peripheral lesions. The presence of bilateral vestibular schwannomas through imaging studies distinguishes NF2 from other neurocutaneous syndromes.@*Case@#This is a case of an 18-year-old male who presented with lower paraparesis with associated hearing loss, cataract, and a few subcutaneous nodules. Centrally located lesions were suspected, thus brain and spine magnetic resonance imaging (MRI) were done revealing bilateral vestibular schwannomas and spine neurofibromas. The patient and family were advised for tumor surveillance, and apprised of surgical intervention once with brainstem compression symptoms.@*Conclusion@#NF2 is a rare debilitating disease that may lead to multiple neurologic deficits. The absence of recommended medical treatment and the multifocality of the tumors leave surgical resection a high-risk treatment option. Early recognition by tumor surveillance may give patients with NF2 a better prognosis and survivability.

Hepatectomía en dos tiempos por metástasis hepáticas bilobares de origen colorrectal: reporte de un caso / Two-stage hepatectomy for bilobar colorectal liver metastases: case report / Hepatectomia em dois estágios para metástases hepáticas bilobares de origem colorretal: relato de um caso

La mitad de los pacientes con cáncer de origen colorrectal desarrollan metástasis hepáticas durante el curso de su enfermedad y de esas el 80% son irresecables. La resecabilidad se define no por la extensión de la hepatectomía, sino por la función del hígado remanente, por lo que para pacientes con ciertos factores favorables se pueden realizar técnicas de remodelación hepática para aumentar el volumen del hígado remanente para que este sea suficiente. La hepatectomía en dos tiempos se basa en procedimientos secuenciales que buscan tratar metástasis hepáticas colorrectales consideradas inicialmente irresecables, logrando la resección completa de las mismas dejando un remanente hepático funcionante suficiente, lo cual no sería posible en un solo acto quirúrgico. El objetivo de este trabajo es presentar el caso clínico de un paciente portador de metástasis hepáticas sincrónicas de origen colorrectal irresecables, que luego de una quimioterapia de conversión, con el fin de aumentar el futuro remanente hepático y evitar falla hepática postoperatoria y realizar una resección oncológica, fue sometido a una hepatectomía en dos tiempos, técnica utilizada con baja frecuencia en nuestro medio, destacando una evolución favorable, con marcadores tumorales en valores normales y sin evidencia imagenológica de recaída local ni sistémica.

Half of colorectal cancer patients develop liver metastases during the course of their disease, 80% of which are unresectable. Resectability is defined not by the extent of the hepatectomy, but by the function of the liver remnant. Therefore, for patients with certain factors, liver remodeling techniques can be performed to increase volume of the remaining liver so that it is sufficient. Two-stage hepatectomy is performed on colorectal liver metastases which are initially considered unresectable in one stage resection procedures, in which sequential procedures are performed in order to achieve complete resection and preserve a sufficient functioning liver remnant. The objective of this paper is to present the case of a patient with unresectable synchronous colorectal liver metastases, in which after conversion chemotherapy, in order to increase the future liver remnant, avoid postoperative liver failure and perform an oncological resection underwent a two-stage hepatectomy, a technique used with low frequency in our setting, highlighting a favorable evolution, with tumor markers in normal values and without imaging evidence of local or systemic relapse.

Metade dos pacientes com câncer colorretal desenvolve metástases hepáticas durante o curso da doença e, desses, 80% são irressecáveis. A ressecabilidade é definida não pela extensão da hepatectomia, mas pela função do fígado remanescente; portanto, para pacientes com certos fatores favoráveis, técnicas de remodelação hepática podem ser realizadas para aumentar o volume do fígado remanescente de forma que seja suficiente. A hepatectomia em dois estágios é baseada em procedimentos sequenciais que buscam tratar metástases hepáticas colorretais inicialmente consideradas irressecáveis, obtendo ressecção completa, deixando um remanescente hepático funcional suficiente, o que não seria possível em um único ato cirúrgico. O objetivo deste trabalho é apresentar o caso clínico de um paciente com metástases hepáticas sincrônicas irressecáveis ​​de origem colorretal, que após quimioterapia de conversão, com o objetivo de aumentar o futuro remanescente hepático e evitar insuficiência hepática pós-operatória e realizar uma ressecção oncológica, foi submetido a dois Hepatectomia em estágio, técnica utilizada com baixa frequência em nosso meio, evidenciando evolução favorável, com marcadores tumorais em valores normais e sem evidências de imagem de recidiva local ou sistêmica.

Profiles of endoglin and vascular endothelial growth factor based on staging and histological grading of colorectal cancer and their relationship with bevacizumab therapy / Perfis da endoglina e do fator de crescimento endotelial vascular com base no estadiamento e na graduação histológica do câncer colorretal e sua relação coma terapia com bevacizumabe

Objective: The present study evaluated the profile of endoglin (CD105) and vascular endothelial growth factor (VEGF) based on staging and histopathological grading of colorectal cancer as well as their relationship with bevacizumab therapy. Methods: A total of 88 cases of colorectal adenocarcinoma were included in the present study. The levels of VEGF and CD105 protein were evaluated with enzymelinked immunosorbent assay (ELISA). Results: There was a significant difference in the level of CD105 (p=0.002) between metastases and non-metastases subjects, showing that CD105 was higher in metastases subjects (4.59 ng/ml). Therewas no significant difference in the level of VEGF based on the presence of metastasis (p=0.625). There was a significant difference in the levels of CD105 (p=0.038) and VEGF (p=0.010) between the subjects who received chemotherapy and those who did not. The CD105 level was higher in the subjects who received chemotherapy (4.43 ng/ml); conversely, the level of VEGF was lower in subjects who received chemotherapy (543.65 pg/ml). There was a statistically significant difference in the levels of CD105 (p=0.003) and VEGF (p=0.002) between subjects who received bevacizumab therapy and subjects who did not. The levels of CD105 were higher in subjects who received bevacizumab therapy (5.11 ng/ml); in contrast, the level of VEGF was higher in subjects who did not receive bevacizumab therapy (645.92 pg/ml). There was a significant positive correlation between CD105 and VEGF in subjects who did not receive bevacizumab (p<0.01). Conclusion: The results of this study support a hypothesis of "escape mechanism" in the failure of anti-angiogenesis therapy (anti-VEGF). (AU)

Objetivo: Este estudo avaliou o perfil da endoglina (CD105) e do fator de crescimento endotelial vascular (FCEV) com base no estadiamento e graduação histopatológica do câncer colorretal, assim como sua relação com a terapia com bevacizumabe. Métodos: No total, 88 casos de adenocarcinoma colorretal foram incluídos no presente estudo. Os níveis das proteínas FCEV e CD105 foram avaliados com ensaio imunoenzimático (ELISA, na sigla em inglês). Resultados Houve uma diferença significativa no nível de CD105 (p=0,002) entre indivíduos commetástases e semmetástases, que indicou que o nível de CD105 émais alto em indivíduos com metástases (4,59 ng/ml). Não houve diferença significativa no nível de FCEV com base na presença de metástases (p=0,625). Houve diferença significativa nos níveis de CD105 (p=0,038) e de FCEV (p=0,010) entre os indivíduos que receberam quimioterapia e os que não receberam. Encontrou-se um nível de CD105 mais alto nos indivíduos que submetidos a quimioterapia (4,43 ng/ml); Em contrapartida, encontrou-se um nível de FCEV mais baixo em indivíduos que submetidos a quimioterapia (543,65 pg/ml). Houve uma diferença estatisticamente significativa nos níveis de CD105 (p=0,003) e de FCEV (p=0,002) entre os indivíduos submetidos e não submetidos à terapia com bevacizumabe. Os níveis de CD105 foram mais elevados em indivíduos submetidos à terapia combevacizumab (5,11 ng/ml); em contraste, observou-se um nível de FCEV mais alto em indivíduos que não foram submetidos à terapia com bevacizumabe (645,92 pg/ml). Houve uma correlação positiva significativa entre CD105 e FCEV em indivíduos que não receberam bevacizumabe (p<0.01). Conclusão: Os resultados deste estudo corroboram a hipótese de "mecanismo de escape" na falha da terapia anti-angiogênica (anti-FCEV). (AU)

Protocolo assistencial de injeções intravítreas do HCPA: degeneração macular relacionada com a idade na forma neovascular / Intravitreal injections for age-related macular degeneration: an HCPA care protocol

A degeneração macular relacionada com a idade na forma neovascular é uma das principais causas de cegueira no mundo e a segunda indicação mais frequente de injeções intravítreas no Hospital de Clínicas de Porto Alegre. O tratamento com injeção intra-vítrea de medicamentos supressores do fator de crescimento endotelial (anti-vascular endothelial growth factor, anti-VEGF), incluindo o bevacizumabe, revolucionou o desfecho visual destes pacientes às custas de múltiplas aplicações mensais. Assim como em outros centros, discrepâncias entre condutas da equipe assistencial e dificuldades logísticas acabam comprometendo a efetividade do tratamento. Portanto, desenvolvemos um protocolo de tratamento para a DMRI-n embasado na literatura, estabelecendo critérios de inclusão, exclusão, regime de tratamento e seguimento do paciente. Com isto, esperamos otimizar a efetividade e assistência do paciente com DMRI-n. (AU)

Age-related macular degeneration in the neovascular form is one of the main causes of blindness in the world and the second most frequent indication of intravitreal injections at Hospital de Clínicas de Porto Alegre. Treatment with intravitreal injection of antivascular endothelial growth factor agents, including bevacizumab, revolutionized the visual outcome of these patients at the expense of multiple monthly applications. As in other centers, discrepancies in care team's approaches and logistical difficulties compromise the effectiveness of treatment. Therefore, we developed a treatment protocol for neovascular age-related macular degeneration (nAMD) based on the literature, establishing criteria for inclusion, exclusion, treatment regimen and patient follow-up. We hope to optimize the effectiveness of treatment in patients with nAMD. (AU)

Effects of bevacizumab on familial epistaxis caused by hereditary hemorrhagic telangiectasia / 中华耳鼻咽喉头颈外科杂志

Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People's Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients' self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t=9.708, P<0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t=6.814, P<0.01; epistaxis duration: 0.85±0.91 vs 3.00±0.73, t=8.845, P<0.01; epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t=10.696, P<0.01; treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t=9.539, P<0.01; anemia: 0.41±0.50 vs 0.89±0.32, t=4.914, P<0.01; blood transfusion: 0.11±0.32 vs 0.41±0.50, t=3.309, P<0.01; ESS standardized score: 2.50±2.45 vs 7.60±1.30, t=9.344, P<0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t=6.864, P<0.01). Among the 27 patients, there were 8 cases of HHT1 (ENG gene) and 19 cases of HHT2 (ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups (P>0.05). There was no significant difference in ESS scores between the two groups before and after treatment (P>0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.

Age-related macular degeneration: a review of current therapies and new treatments / Degeneração macular relacionada à idade: revisão das terapias atuais e novos tratamentos

ABSTRACT Age-related macular degeneration is the leading cause of vision loss in elderly individuals, as well as a medical and socio-economic challenge. The treatment of dry age-related macular degeneration is based on vitamin supplementation. New treatment studies are focused on preventing the progression of degeneration and repopulating the atrophic macula. Recently, research on the treatment of neovascular age-related macular degeneration experienced a breakthrough with the advent of anti-vascular endothelial growth factor inhibitors. Nevertheless, despite the fact that ranibizumab, aflibercept, and bevacizumab are effective in reducing severe visual impairment, patients usually lose some vision over time. Therefore, the search for new therapies and diagnostic methods is fundamentally important. Current studies are focused on new anti-vascular endothelial growth factor drugs, nucleoside reverse transcriptase inhibitors, antibody against sphingosine-1-phosphate, anti-platelet-derived growth factor, gene therapy, and RNA interference. The results of ongoing clinical studies may improve the therapy of age-related macular degeneration.

RESUMO Degeneração macular relacionada à idade (DMRI) é a principal causa de perda de visão em pessoas idosas. É também um desafio médico e socioeconômico. O tratamento da degeneração macular relacionada à idade seca baseia-se na suplementação vitamínica. Novos tratamentos estão focados na prevenção da progressão da degeneração e tentativas de repovoar a mácula atrófica. A degeneração macular relacionada à idade neovascular experimentou um grande avanço com o advento dos inibidores do fator de crescimento endotelial anti-vascular (anti-VEGF); no entanto, apesar do ranibizumab, aflibercept e bevacizumab serem eficazes na redução do comprometimento visual grave, os pacientes geralmente per­dem visão ao longo do tempo. Portanto, a busca por novas terapias, tratamentos e diagnósticos é de fundamental importância. Os estudos estão focados em novos fármacos sobre fator de crescimento endotelial anti-vascular, inibidores nucleosideos da transcriptase reversa, anticorpos contra esfingosina-1-fosfato, fator de crescimento derivado de plaquetas, terapia genética e RNA de interferência. A terapia para degeneração macular relacionada à idade está prestes a melhorar como resultado desses estudos clínicos em andamento.

Changes in the ganglion cell complex thickness after anti-VEGF treatment for diabetic macular edema / Alterações na espessura do complexo de células ganglionares após tratamento anti-VEGF para edema macular diabético

ABSTRACT Purpose: To assess tomographic ganglion cell complex changes in patients with diabetic macular edema treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). Methods: We analyzed data from 35 eyes of 35 previously untreated patients in whom diabetic macular edema improved after three loading doses of anti-VEGF injection and who did not receive repeated injections. We recorded spectral domain-optical coherence tomography assessments of ganglion cell complex and central macular thickness at baseline and monthly for three months, and on the sixth and ninth month after treatment. We compared the results with those of the unaffected eyes in the same patients and with those in a control group of patients with diabetic macular edema who were untreated. Results: The mean age of the patients in the treatment group was 60 ± 4.38 years. The foveal thicknesses measured using optical coherence tomography decreased significantly from baseline to the third month post-injection (p<0.05). The mean ganglion cell complex thickness was 115.08 ± 16.72 µm before the first injection and 101.05 ± 12.67 µm after the third injection (p<0.05). The mean ganglion cell complex was 110.04 ± 15.07 µm on the sixth month (p>0.05) and 113.12 ± 11.15 µm on the ninth month (p>0.05). We found a significant difference between the patients and the control group in terms of mean ganglion cell complex thickness on the second- and third-months post-injection (p<0.05). Conclusion: Our study showed that the ganglion cell complex thickness in patients with diabetic macular edema decreased after the anti-VEGF injections. We cannot ascertain whether the ganglion cell complex thickness decreases were due to effects of the anti-VEGF agents or to the natural disease course.

RESUMO Objetivo: Avaliar as alterações do complexo tomográfico das células ganglionares em pacientes com edema macular diabético tratados com injeções intravítreas do fator de crescimento endotelial anti-vascular (anti-VEGF). Métodos: Analisamos dados de 35 olhos de 35 pacientes previamente não tratados nos quais o edema macular diabético melhorou após três doses de injeção de anti-VEGF e que não receberam injeções repetidas. Registramos avaliações da tomografia de coerência óptica de domínio espectral do complexo de células ganglionares e da espessura macular central na linha de base e mensalmente por três meses e, também no sexto e nono mês após o tratamento. Comparamos os resultados com os olhos não afetados nos mesmos pacientes e com os de um grupo controle de pacientes com edema macular diabético que não foram tratados. Resultados: A média da idade dos pacientes no grupo de tratamento foi de 60 ± 4,38 anos. As espessuras foveais medidas pela tomografia de coerência óptica diminuiram significativamente desde o início até o terceiro mês após a injeção (p<0,05). A espessura média do complexo de células ganglionares foi de 115,08 ± 16,72 µm antes da primeira injeção e 101,05 ± 12,67 µm após a terceira injeção (p<0,05). A média do complexo de célula ganglionar foi de 110,04 ± 15,07 µm no sexto mês (p>0,05) e 113,12 ± 11,15 µm no nono mês (p>0,05). Encontramos uma diferença significativa entre os pacientes e o grupo controle quanto à média da espessura do complexo de células ganglionares no segundo e terceiro meses após a injeção (p<0,05). Conclusão: Nosso estudo mostrou que a espessura do complexo de células ganglionares em pacientes com edema macular diabético diminuiu após as injeções de anti-VEGF. Não podemos determinar se a diminuição da espessura do complexo de células ganglionares ocorreu devido aos efeitos dos agentes anti-VEGF ou ao curso natural da doença.

Actualización de medicamentos asociados a necrosis avascular de los maxilares: perspectiva y revisión de literatura / Update of medications associated with avascular necrosis of the jaws: a perspective and literature review

La osteonecrosis de los maxilares está definida como la exposición de hueso necrótico en la región maxilofacial al menos por ocho semanas en pacientes que están recibiendo medicamentos antirresortivos para el tratamiento del cáncer primario o metastásico hacia el hueso, osteoporosis o enfermedad de Paget, sin historia previa de radiación. Desde el año 2003, la terminología utilizada estaba en relación con los bifosfonatos, en la actualidad ha sido introducido el término osteonecrosis de los maxilares relacionada por medicamentos (OMAM). La cirugía oral (implantología o cirugía periapical) incrementa el riesgo de OMAM, así como los desbalances concomitantes de la salud oral (inflamación dental y formación de abscesos). Las estrategias conservadoras en el tratamiento varían desde el cuidado local conservador hasta la resección quirúrgica radical del hueso necrótico. En el presente artículo se expone un análisis sistemático retrospectivo de la literatura en páginas como PubMed, ScienceDirect y Springer, Cochrane Library. Con el objetivo de resaltar el aumento de la incidencia de OMAM a nivel mundial con el uso de antirresortivos y otros medicamentos asociados en su patogenia en el Hospital Regional «General Ignacio Zaragoza¼ del ISSSTE, UNAM, en la Ciudad de México (AU)

Osteonecrosis of the jaws is defined as the exposure of necrotic bone in the maxillofacial region for at least 8 weeks in patients receiving antiresorptive medications for the treatment of primary or metastatic cancer towards the bone, osteoporosis, or Paget's disease, without previous history of radiation. Since 2003, the terminology used was related to bisphosphonates, the term medication-related osteonecrosis of the jaws has now been introduced. Oral surgery (implantology or periapical surgery) increases the risk of avascular necrosis, as well as concomitant imbalances in oral health (dental inflammation and abscess formation). Conservative strategies in treatment vary from conservative local care to radical surgical resection of the necrotic bone. In this article, a systematic retrospective analysis of the literature is presented on pages such as PubMed, Science Direct and Springer, Cochrane Library. And in which the objective is to highlight the increase in the incidence of medication related osteonecrosis of the jaws worldwide with the use of antiresorptive, and other associated medications in its pathogenesis at the Hospital Regional «General Ignacio Zaragoza¼ ISSSTE, UNAM in Mexico City (AU)

Standard treatment with bevacizumab as targeted therapy in cervical cancer

ABSTRACT Metastatic, recurrent, or persistent disease in cervical cancer has a poor prognosis. Historically, this group of patients has had limited treatment options, even with the best cytotoxic treatments (platinum-based chemotherapy [CT] doublets). Therefore, investigating new medications that help improve the patient's quality of life and survival has been essential. Angiogenesis has been shown to play a critical role in tumor cell growth and survival. Bevacizumab is a recombinant humanized monoclonal G1 immunoglobulin targeted against vascular endothelial growth factor. The combination of CT and bevacizumab is associated with an increase in overall survival as well as in progression-free survival and response rates.

Informe diário de evidências COVID-19: busca realizada em 31 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 31, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 12 artigos e 6 protocolos.

Survey among retina specialists in Brazil about inflammatory reactions after intravitreal antiangiogenic therapy / Levantamento entre especialistas em retina no Brasil sobre reações inflamatórias após terapia antiangiogênica intravítrea

ABSTRACT Purpose: This survey aimed at assessing the clinical characteristics of patients with inflammatory reactions after intravitreal injection of antiangiogenic agents and the techniques employed by Brazilian retina specialists. Methods: We sent an 18-item questionnaire electronically to retina specialists who are using antiangiogenic agents. We got the responses between September 21 and December 23, 2018. Results: A total of 58 retina specialists participated. Most of them were from Southeastern Brazil (50%), 82.8% were dedicated to both medical and surgical practices, and 86.2% had practiced for more than 5 years. Respondents reported a mean number of 2.14 ± 1.63 patients with inflammation, 44.8% with panuveitis, and 79.3% with onset of symptoms within 72 h. Specialists used aflibercept (53.4%), bevacizumab (29.3%), and ranibizumab (27.6%). Most patients were treated with steroid drops (70.7%), and their inflammation subsided after 11.5 ± 11.5 days (86.2% lacked irreversible complications). The specialists blamed the syringe as the cause of the inflammation in 25.9% of the cases, 41.4% used Becton-Dickinson Ultra-Fine syringes, 43.1% injected the drug at room temperature, and 37.9% removed the air (53.4% by flicking the syringe). Most specialists did not detect silicone oil (67.2%), but 17.2% of them performed vitrectomies to remove vitreous opacities. Finally, 44.8% of specialists injected the same antiangiogenic agent in an eye with prior inflammatory reaction without further inflammation. Conclusions: Most specialists reported cases of early-onset inflammation after intravitreal injection of antiangiogenic agents. The incidence of irreversible complications was low. Aflibercept was the most common agent used. The causes of inflammation remain unknown, but we formulated some relevant hypotheses.

RESUMO Objetivo: Esta pesquisa teve como objetivo avaliar as características clínicas de pacientes com reações inflamatórias após injeção intravítrea de agentes antiangiogênicos e as técnicas empregadas por especialistas em retina brasileiros. Métodos: Enviamos eletronicamente um questionário de 18 itens para especialistas em retina que usam agentes antiangiogênicos. Recebemos as respostas entre 21 de setembro e 23 de dezembro de 2018. Resultados: Um total de 58 especialistas em retina participaram. A maioria era do Sudeste do Brasil (50%), 82,8% eram dedicados a práticas médicas e cirúrgicas e 86,2% praticavam há mais de 5 anos. Os entrevistados informaram um número médio de 2,14 ± 1,63 pacientes com inflamação, 44,8% com panuveíte e 79,3% com início dos sintomas dentro de 72 horas. Especialistas utilizaram aflibercepte (53,4%), bevacizumabe (29,3%) e ranibizumabe (26=7,6%). A maioria dos pacientes foi tratada com colírios de esteroides (70,7%), e sua inflamação diminuiu após 11,5 ± 11,5 dias (86,2% não apresentaram complicações irreversíveis). Os especialistas responsabilizaram a seringa como causa da inflamação em 25,9% dos casos, 41,4% usaram seringas Becton-Dickinson Ultra-Fine, 43,1% injetaram a droga em temperatura ambiente e 37,9% removeram o ar (53,4% sacudindo a seringa). A maioria dos especialistas não detectou óleo de silicone (67,2%), mas 17,2% realizaram vitrectomias para remoção de opacidades vítreas. Finalmente, 44,8% dos especialistas injetaram o mesmo agente angiogênicos em um olho com reação inflamatória prévia, sem surgimento de nova inflamação. Conclusões: A maioria dos especialistas relatou casos de inflamação de início precoce após injeção intravítrea de agentes antiangiogênicos. A incidência complicações irreversíveis foi baixa. Aflibercepte foi o agente mais frequentemente usado. As causas da inflamação permanecem desconhecidas, embora formulamos algumas hipóteses relevantes.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective / Estudo de custo-efetividade de tratamentos para a degeneração macular relacionada à idade: uma perspectiva brasileira

ABSTRACT Purpose: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. Methods: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. Results: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. Conclusions: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

RESUMO Objetivo: Estudar o custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade neovascular. Métodos: Utilizamos um modelo de árvore de decisão para analisar a relação custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade, sob a perspectiva do Sistema Único de Saúde. O ranibizumabe e bevacizumabe foram administrados a pacientes com o mesmo procedimento de tratamento, e a diferença nos custos do tratamernto foi calculada com base no custo dos medicamentos. Os custos diretos foram estimados utilizando as informações fornecidas pelo SUS. A efetividade foi determinada em anos de vida ajustados pela qualidade (QALY) baseados em valores de utilidade em deficiênciavisual. A razãoincremental custo-efetividadefoicalculada comparando os dois tratamentos. O horizonte analítico foi de um ano. Resultados: A análise da árvore de decisão mostrou que a diferença na efetividade do tratamento foi de 0,01 QALY. A razão incremental de custo-efetividade mostrou que o tratamento com ranibizumabe exigiu um custo anual incremental de R$ 2 milhões para gerar um QALY adicional, em comparação ao bevacizumabe. Conclusões: Do ponto de vista do SUS, o bevacizumabe é mais custo-efetivo que o ranibizumabe no tratamento da degeneração macular relacionada à idade neovascular. O seu uso poderia gerar uma grande economia anual para o orçamento em saúde.