Osteonecrose dos maxilares relacionada ao uso demedicamentos: características patológicas, diagnóstico,prevenção e estratégias terapêuticas / Medication-related osteonecrosis of the jaws: pathological characteristics, diagnosis, prevention and therapeutic strategies

Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)

Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)

Dill seed oil as a possible contraceptive agent: antiangiogenic effects on endothelial cells

Abstract Dill (Anethum graveolens L.) essential oil is wide spread in the food, beverage and pharmaceutical sectors. Dill is a member of the Apiaceae (Umbelliferae) family. It has the following biological activities: antioxidant, antifungal, antibacterial, antimicrobial, antihyperlipidemic, antihypercholesterolemic, antispasmodic, antiproliferative and anti-inflammatory. Aqueous extract of dill seed has reported effects on sex hormones and infertility potential. Moreover, boiled dill seed has an impact on reducing labor duration in giving birth. Implantation and placentation are necessary for a healthy pregnancy in the early stages. Angiogenesis is responsible for these essential processes. This study aimed to investigate dill seed oil's cytotoxic and antiangiogenic effects on rat adipose tissue endothelial cells (RATECs). Dill seed oil showed dose-dependent cytotoxicity on RATECs. It disrupted endothelial tube formation and depolymerized F-actin stress fibers. According to this study, depolymerization of F-actin stress fiber by dill seed oil could inhibit angiogenesis by suppressing endothelial cell proliferation, tube formation and motility. In other words, dill seed oil can be a new anti-angiogenic agent and a novel contraceptive.

Osteonecrosis de los maxilares: reacción medicamentosa / Osteonecrosis of the jaws: drug reaction

La osteonecrosis de los maxilares (ONM) secundaria al consumo de medicamentos antirresortivos y antiangiogénicos es una patología oral que afecta el funcionamiento del organismo de los seres humanos no sólo a nivel bucal, sino que disminuye su calidad de vida y aumenta su morbilidad. La ONM se define como la presencia de hueso necrótico expuesto que puede ser explorado mediante una fístula en el territorio maxilofacial, que se mantiene durante un periodo mínimo de ocho se- manas. Los fármacos antirresortivos y antiangiogénicos son indicados a pacientes que presentan patologías osteometabólicas, cáncer, entre otras, de ahí la importancia de mantener una estrecha relación entre médico tratante-odontólogo-paciente. El propósito de este artículo es establecer un protocolo de cuidado oral básico y definir las funciones del médico tratante, cirujano dentista y cirujano maxilofacial mediante una revisión bibliográfica con el fin de crear una propuesta preventiva para el tratamiento de estos pacientes (AU)

Medication-related osteonecrosis of the jaw (MRONJ), secondary to the consumption of antiresorptive and antiangiogenic drugs is an oral pathology that affects the functioning of the human body, not only at the oral level, but also decreasing their quality of life and increasing their morbidity. MRONJ is defined as the presence of exposed necrotic bone that can be explored through a fistula in the maxillofacial territory, which is maintained for a minimum period of eight weeks. Antiresorptive and antiangiogenic drugs are indicated for patients with osteometabolic pathologies, cancer, among others. For the same reasons, the importance of maintaining a close relationship between the treating physician, dentist and patient. The purpose of this article is to establish a clinical guide for basic oral care and define the functions of the treating physician, dental surgeon and maxillofacial surgeon through a bibliographic review; in order to create a preventive proposal for the treatment of these patients (AU)

The tale of lenalidomide clinical superiority over thalidomide and regulatory and cost-effectiveness issues / A narrativa de que a lenalidomida é clinicamente superior à talidomida, e questões regulatórias e de custo-efetividade

Abstract In April 2017, the National Sanitary Surveillance Agency (ANVISA-Brazil) approved lenalidomide (LEN) for multiple myeloma (MM) and myelodysplastic syndrome. ANVISA had rejected the first application in 2010, and denied a request for reconsideration in 2012. The reason for rejection was the lack of comparative effectiveness studies proving that LEN was more effective than thalidomide (THAL), a strictly controlled drug regulated by Federal law 10.651/2003 and dispensed to patients (at no costs) through public health system units and hospitals. ANVISA unexplained retreat on the LEN approval for marketing was an unquestionable triumph of the lobbying that ensued the denial, at the forefront of which were politicians, Congress members, patient organizations and medical societies. Two randomized (phase III) trials and three observational (case-control and population-based cohort) compared the effectiveness of THAL- versus LEN-based therapies in MM. Overall, these studies showed no difference in efficacy between LEN- and THAL-based therapies. LEN caused less neuropathy, and more severe hematologic adverse effects. It is much costlier than THAL, and substitution of THAL by LEN shall raise considerably public healthcare costs in Brazil.

Resumo A Agência Nacional de Vigilância Sanitária (ANVISA) aprovou em abril de 2017 a lenalidomida (LEN) para o mieloma múltiplo (MM) e síndrome mielodisplásica. A ANVISA havia negado o registro em 2010, e indeferido um recurso apresentado em 2012. O motivo do indeferimento foi a falta de estudos comparativos de efetividade demonstrando que LEN era mais eficaz do que a talidomida (TAL), um medicamento rigorosamente controlado pela lei federal 10.651/2003 e dispensado gratuitamente a pacientes através de unidades de saúde e hospitais públicos. O recuo não explicado da ANVISA em relação ao registro da LEN foi um inquestionável triunfo do lobby que sucedeu a recusa inicial do registro, a frente do qual estavam políticos, membros do Congresso, associações de pacientes e sociedades médicas. Dois ensaios randomizados (fase III) e três estudos observacionais (caso-controle e coorte de base populacional) compararam a efetividade de terapias para o MM com TAL- e com LEN. Em conjunto, esses estudos mostraram que não havia diferenças quanto a eficácia de tratamentos com LEN- e aqueles com TAL. A LEN causou menos neuropatias, e efeitos adversos hematológicos mais graves. Ela é muito mais cara do que a TAL, e a substituição da TAL pela LEN aumentará muito os custos da assistência pública à saúde no Brasil.

Risk profile for antiangiogenic agent-related osteonecrosis of the jaws / Perfil de risco para osteonecrose dos maxilares associada a agentes antiangiogênicos

ABSTRACT To establish the profile of patients who developed antiangiogenic agent-related osteonecrosis of the jaws, and identify the treatments currently used in dental management. We searched the PubMed®/Medline® and Scopus databases using the words "osteonecrosis AND antiangiogenic therapy", with the following inclusion criteria: articles published in English, case reports, available online, and for an unlimited period. Of the 209 articles retrieved, 18 were selected, for a total of 19 case reports, since one article included two cases that met the inclusion criteria for this study. Medication-related osteonecrosis of the jaws is characterized by exposure of necrotic bone in the oral cavity that does not heal over a period of 8 weeks in patients with no previous history of radiation therapy. Antiangiogenic drugs are indicated in the treatment of certain tumors, since they stop the formation of new blood vessels, controlling tumor growth and the chance of metastasis. Dental prevention is essential in patients who will be put on antiangiogenic agents, to minimize the risk for osteonecrosis.

RESUMO Traçar o perfil dos pacientes que desenvolveram osteonecrose dos maxilares associada a agentes antiangiogênicos e identificar os tratamentos realizados atualmente no manejo odontológico. Foi realizada busca nas bases de dados PubMed®/Medline® e Scopus por meio dos descritores "osteonecrosis AND antiangiogenic therapy", sendo utilizados os critérios de inclusão: artigos publicados em inglês, relato de caso, disponíveis on-line e por período ilimitado. Após análise dos 209 artigos encontrados, foram selecionados 18 artigos para este estudo, resultando em 19 relatos de caso, visto que um dos artigos apresentou dois casos que se enquadravam nos critérios de inclusão. A osteonecrose dos maxilares associada a medicamentos é caracterizada pela exposição de osso necrótico na cavidade oral que não cicatriza em um período de 8 semanas em pacientes que não foram submetidos à radioterapia. Os medicamentos antiangiogênicos são indicados no tratamento de alguns tumores, pois impedem o crescimento de novos vasos sanguíneos, controlando o crescimento do tumor e a chance de metastização. Torna-se imprescindível a realização de prevenção odontológica do paciente a ser submetido a uso de antiangiogênicos visando a minimizar as chances de desenvolvimento da osteonecrose.

Prevención de osteonecrosis asociada a medicamentos y ensayo clínico multicéntrico, Facultad de Odontología, Universidad de Buenos Aires / Prevention of drug-related osteonecrosis and multicentric clinical trial, School of Dentistry, University of Buenos Aires

La osteonecrosis asociada a medicamentos (ONAM) es un efecto adverso poco frecuente pero potencialmente serio que afecta a pacientes que reciben o recibieron tratamiento con drogas antirresortivas o antiangiogénicas. A partir de una revisión narrativa de la literatura, el presente artículo aporta conceptos básicos e información actualizada acerca de incidencia, factores de riesgo y prevención de ONAM desde la perspectiva de la Práctica Basada en la Evidencia. Además pone en conocimiento a la comunidad profesional de la Facultad de Odontología de la Universidad de Buenos Aires acerca de las actividades de investigación clínica llevadas a cabo en este área en la Cátedra de Cirugía y Traumatología Buco-Máxilo-Facial I de nuestra casa de estudios (AU)

Medicine related osteonecrosis of the jaws (MRONJ) is a rare but potentially serious side effect experienced by patients receiving treatment with antiresorptive or antiangiogenic drugs. Through a narrative review of the literature, this paper provides basic concepts and updated data about incidence, risk factors and prevention of MRONJ from the Evidence Based Practice perspective. It also informs the professional community of the School of Dentistry of the University of Buenos Aires about the clinical research activities carried out in this area in the Oral and Maxillofacial Surgery I Department (AU)

The clinical efficacy and safety of paclitaxel combined with avastin for NSCLC patients diagnosed with malignant pleural effusion

Summary Objective: The current study aimed to investigate the clinical efficacy of paclitaxel combined with avastin for non-small cell lung cancer (NSCLC) patients diagnosed with malignant pleural effusion (MPE). Method: Total of 33 patients diagnosed with NSCLC as well as malignant pleural effusion were included. All of them received paclitaxel (175 mg/m2) and avastin (5 mg/kg). Clinical efficacy was evaluated using the total response rate, overall survival, progression-free survival and changes in MPE volume. Adverse events and rates of toxicities were examined as well. Results: The total response rate reached 77% while the overall survival and the median progression-free survival were respectively 22.2 months and 8.4 months. Toxicities of grade 3-4 consisted of neutropenia in 57% of patients, anemia in 17% of them, febrile neutropenia in 11%, as well as anorexia in 7%. No treatment-correlated deaths were found. Conclusion: Paclitaxel combined with avastin decreased MPE volume and increased survival rate of NSCLC patients via inhibiting vascular endothelial growth factor expression.

Análise da variação da pressão intraocular após injeção intravítrea de ranibizumabe / Analysis of intraocular pressure variation after intravitreal injection of ranibizumab

Resumo Objetivo: O tratamento com anti-angiogêncios é uma das modalidades mais utilizadas em patologias relacionadas ao edema macular. A injeção intravítrea de um inibidor do VEGF-A tem alta efetividade, porém está relacionada com efeitos adversos, como o aumento da pressão intraocular. O objetivo deste estudo foi avaliar a variação da pressão intraocular (PIO) em pacientes que se submeteram a injeções intravítreas de ranibizumabe, a variação de acordo com facia e com história de injeções prévias. Métodos: Este foi um estudo um estu-do observacional transversal. Foram incluídos todos os pacientes submetidos a injeções intravítreas com diagnóstico de degeneração macular relacionada à idade exsudativa, oclusão de veia central da retina com edema macular, ou edema macular diabético. A pressão intraocular foi aferida antes da injeção, imediatamente após e 30 minutos após a injeção com tonômetro portátil. Resultados Foram realizadas 143 injeções intravítreas, restando para a análise 96 injeções realizadas em 55 participantes. A comparação entre a PIO antes e 30 minutos após a injeção intravítrea mostrou-se estatisticamente significativa com PIO final maior que a inicial (p<0,0001) em pacientes com edema macular diabético. Pacientes fácicos e afácicos não mostraram diferenças significativas com relação a variação da PIO. Quando analisados apenas os participantes que haviam recebido injeções prévias, não foi encontrado uma variação significativa. Conclusão: Concluímos neste estudo que existe uma diferença significativa entre a pressão intraocular antes e 30 minutos após a injeção intravítrea de ranibizumabe em pacientes com edema macular diabético, mos-trando que esse período de tempo não foi suficiente para a regressão da PIO ao valor pré-injeção. Não encontramos diferenças significativas entre outros grupos, comparação entre fácicos e afácicos, nem em pacientes que haviam recebido injeções prévias.

Abstract Objective: Treatment with anti-angiogenic drugs is one of the most widely used modalities of treatment of macular edema related conditions. Intravitreal injection of a VEGF-A inhibitor is highly effective, but is related to adverse effects such as increased intraocular pressure. The objective of this study was to evaluate intraocular pressure (IOP) variation in patients who underwent intravitreal injections of ranibizumab, variation according to phakic/aphakic and history of previous injections. Methods: This was a cross-sectional observational study. All patients submitted to intravitreal injections with diagnosis of exudative age-related macular degeneration, retinal central vein occlusion with macular ede-ma, or diabetic macular edema were included. The IOP was measured before the injection, immediately after and 30 minutes after the injection with a portable tonometer. Results: 143 intravitreal injections were performed, with 96 injec-tions performed in 55 participants. The comparison between IOP before and 30 minutes after intravitreal injection showed to be statistically significant with higher than initial IOP (p <0.0001) in patients with diabetic macular edema. Phakic and aphakic patients did not show significant differences regarding IOP variation. When only those participants who had received previous injections were analyzed, no significant variation was found. Conclusion: We conclude in this study that there is a significant difference between intraocular pressure before and 30 minutes after intravitreal injection of ranibizumab in patients with diabetic macular edema, showing that this period of time was not sufficient for regression of IOP at the pre-injection value . We did not find significant differences between other groups, comparing phakic and aphakic patients, nor in patients who had received previous injections.

Incidence of anterior segment neovascularization during intravitreal treatment for macular edema secondary to central retinal vein occlusion / Incidência de neovasos de segmento anterior durante o tratamento de edema macular secundário a oclusão da veia central da retina

ABSTRACT Purpose: To analyze the effects of injections of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) on the incidence rates of anterior segment neovascularization (ASN) and neovascular glaucoma (NVG) in patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In this prospective, randomized, double-masked, sham-controlled study, 35 patients with macular edema following CRVO were randomized to intravitreal bevacizumab, intravitreal triamcinolone acetonide, or sham injections during the first 6 months of the study. The primary outcome was the incidence rate of ASN at month 6. The secondary outcomes were the mean changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography over time to month 12. Results: ASN developed in 8 (22.86%) eyes, including 5 (62.50%) eyes in the sham group and 3 (37.50%) eyes in the IVTA group, during 12 months of fol low-up (p=0.009). BCVA differed significantly (p<0.05) among the groups only at month 1. CFT did not differ significantly (p<0.05) among the groups over 12 months. NVG required surgery and developed in one eye despite laser treatment. Conclusion: Early treatment with intravitreal antivascular endothelial growth factor therapy decreases the rates of ASN and NVG after CRVO.

RESUMO Objetivo: Analisar as taxas de incidência de neovascularização do segmento anterior (NSA) e de glaucoma neovascular (GNV), em pacientes com edema macular secundário a oclusão de veia central da retina (OVCR), em tratamento com injeções intravítreas de triamcinolona (IVTA) ou bevacizumab (IVB). Métodos: Neste estudo prospectivo, randomizado, duplo mascarado e sham controlado, 35 pacientes com edema macular secundário a OVCR foram randomizados para IVB, IVTA ou para o grupo controle (sham), durante os 6 primeiros meses do estudo. O desfecho primário foi a taxa de incidência de NSA no mês 6. Os desfechos secundários foram alterações médias da acuidade visual corrigida (BCVA) e espessura foveal central (EFC) ao exame de tomografia de coerência óptica, até o mês 12. Resultados: NSA ocorreu em oito (22,86%) olhos, cinco (62,50%) olhos no grupo sham e três (37,50%) olhos no grupo tratado com injeções intravítreas de Triamcinolona, Não houve nenhum caso com NSA no grupo tratado com bevacizumab durante 12 meses de acompanhamento (p=0,009). A BCVA apresentou diferença estatisticamente significante (p<0,05) entre os grupos, somente no mês 1. A EFC não apresentou diferenças estatisticamente significantes (p<0,05) entre os grupos ao longo dos 12 meses. GNV ocorreu em um olho apesar do tratamento com laser e este paciente necessitou de intervenção cirúrgica. Conclusão: O tratamento precoce com injeções intravítreas de Anti VEGF podem diminuir as taxas de neovascularização do segmento anterior e glaucoma neovascular após oclusão de veia central da retina.

Seguridad y eficacia del sorafenib en el carcinoma renal metastasico avanzado que progresa despues del tratamiento de primera linea con sunitinib / Safety and efficacy of sorafenib in advanced metastatic renal cell carcinoma progressing after first-line treatment with sunitinib

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del medicamento sorafenib a su uso, en pacientes con carcinoma renal metastásico que progresa al tratamiento de primera línea con sunitinib. Aspectos Generales: El carcinoma de células renales (CCR) es un tipo de cáncer del riñon que se origina en las células de los túbulos renales y contienen muchos vasos sanguíneos. El CCR es responsable del 80 al 85% de las neoplasias renales primarias. Cerca del 8% del resto de las otras neoplasias provienen de las células transicionales de la pelvis renal. Tecnología Sanitaria de Interés: Sorafenib: Sorafenib es un inhibidor multiquinasa que inhibe el desarrollo de los vasos sanguíneos del tumor y la proliferación de las células tumorales. Esta droga tiene una acción dual, inhibiendo la casa cascada raf y los receptores de los factores de crecimiento derivado de plaquetas (PDGF) y de crecimiento endotelial vascular (VEGF), presentes en las células tumorales, en las células endoteliais y en los pericitos. El Sorafenib está autorizado para el tratamiento de pacientes con CCR avanzado en quienes el tratamiento con Interferón alfa o interleuquina-2 han fallado o está contraindicado. Sorafenib se administra oralmente con dosis recomendadas para el CCR avanzado de 400 mg dos veces al día. El tratamiento debe interrumpirse cuando aparezcan eventos adversos inaceptables para el paciente. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del sorafenib como tratamiento de segunda línea en pacientes con CCRm o avanzado progresivo a un tratameinto de primera líena con sunitinib, en las bases de datos de OVID MEDLINE y TRIPDABASE. También se hizo una búsqueda adicional en www.clinicals.ogv, para poder identificar ensayos en desarrollo. Adicionalmente, se hizo una búsqueda dentro de la inforamción generada por grupos que realizan revisiones sistemáticas, evalución de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excelence (NICE) y la European Society for Medical Oncology (ESMO). RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica para el sustento del uso de sorafenib como tratamiento de segunda línea en pacientes con CCRM que progresaron a pesar del tratamiento de primera línea con sunitinib. Solo se identificaron dos GPC que cumplieram los criterios de elegibilidad. CONCLUSIONES: no se ha encontrado evidencia respecto al beneficio y riesgo del uso de sorafenib como tratamiento de segunda línea en pacientes con CCRm que progresan después del tratamiento con sunitinib, respecto al tratamiento de soporte o placebo. Las guías identificadas en esta evaluación recomiendan el uso de sorafenib solo en pacientes que progresan después de recibir tratamiento a base de citoquinas, pero no está incluido en las recomendaciones si el paciente progreso después de recibir medicamentos dirigidos a VEGF. Otros medicamentos diferentes a sorafenib vienen siendo evaluados en pacientes con CCRm progresaron después de recibir medicamentos a los VEGF. Dado que no existe evidencia que responda a la pregunta PICO de esta evaluación, el Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, no aprueba el uso de sorafenib para el tratamiento de pacientes con CCRm que progresarion después del tratamiento con sunitinib.

Trastornos vasculares por antiangiogénicos / Vascular disorders due to antiangiogenic

Los eventos tromboembólicos cerebrales están asociados con secuelas permanentes y con deterioro de la calidad de vida. Sangrados, trastornos venosos y arteriales han sido descriptos con el uso de agentes antiangiogénicos. Presentamos un caso con sarcoma mixoide que desarrolló un accidente cerebrovascular isquémico mientras estaba siendo tratado con sorafenib. Repasamos también las drogas usadas en oncología que podrían estar asociadas con eventos tromboembólicos arteriales o venosos. Los médicos tratantes deberían monitorear a los pacientes que reciben agentes antiangiogénicos en relación a síntomas neurológicos y, en ausencia de otras etiologías, la pronta suspensión de la droga debería ser considerada (AU)

The cerebral thromboembolic events are linked with permanent sequelae and deterioration in quality of life. Bleeding, venous and arterial thromboembolic events have been described with antiangiogenics agents. We report a case with myxoid sarcoma that developed a cerebrovascular accident while on sorafenib treatment. We also reviewed drugs used in oncology that could be associated with arterial and venous thromboembolic events. Physicians should monitor patients receiving antiangiogenics agents for neurologic symptoms and in the absences of other etiology, prompt discontinuation of these drugs should be considered (AU)

Anatomical and visual outcomes of ranibizumab injections in retinal pigment epithelium tears / Resultados anatômicos e visuais de injeções de ranibizumab em roturas do epitélio pigmentado da retina

ABSTRACT Purpose: To report the anatomical and visual results in patients diagnosed as having retinal pigment epithelium (RPE) tears after receiving ranibizumab injections. Methods: Eyes diagnosed as having RPE tears with a minimum 6-month follow-up were retrospectively evaluated. Each eye was treated with at least three doses of ranibizumab at monthly intervals. Best-corrected visual acuity (BCVA), anterior segment findings, intraocular pressure, and fundus examination results were evaluated during control visits. Color fundus photography, fundus fluorescein angiographies, fundus autofluorescence, and spectral domain optical coherence tomography (SD-OCT) images were obtained. The height of pigment epithelial detachment (PED) was measured by SD-OCT. Results: Twelve eyes with RPE tears were studied. Nine eyes (75%) developed RPE tears during ranibizumab injections for choroidal neovascularization (eight eyes with vascularized PED and one eye with choroidal osteoma), and tears occurred in three eyes before any injections. The median number of ranibizumab injections after diagnosis of RPE tears was 3 (min 2, max 5). In the most recent follow-up visit, there was no statistically significant correlation between the grade of RPE and logMAR of BCVA (p>0.05, r=0.112). Eight of twelve eyes had PED, and seven of these had irregular PED contours before injection therapy. The mean PED height was 447 ± 122 µm. Conclusions: In this series, RPE tears developed mostly after intravitreal anti-VEGF injections for vascularized PED. Increased vertical height and irregular contours of the PEDs can be risk factors for the formation of RPE tears. The continuation of anti-VEGF therapy after tear formation is beneficial for vision improvement in eyes with RPE tears. .

RESUMO Objetivo: Apresentar os resultados anatômicos e visuais de injeções de ranibizumab em pacientes que foram diagnosticados com roturas do epitélio pigmentado da retina (RPE). Métodos: Olhos com um mínimo de seis meses de acompanhamento após diagnóstico de roturas do RPE foram avaliados retrospectivamente. Cada olho foi tratado com, pelo menos, três doses de ranibizumab em intervalos mensais. Acuidade visual com a melhor correção (BCVA), achados do segmento anterior, pressão intraocular e exames de fundo de olho foram avaliados nas visitas de controle. Retinografia colorida, angiografias fluoresceínicas, autofluorescência de polo posterior e tomografia de coerência óptica imagens de domínio espectral (SD-OCT) foram obtidos. A altura do descolamento do epitélio pigmentado (PED) foi medida com SD-OCT. Resultados: Doze olhos com roturas do epitélio pigmentado da retina foram incluídos no estudo. Nove olhos (75%) desenvolveram roturas do epitélio pigmentado da retina durante as injeções ranibizumab para neovascularização de coroide (oito olhos com descolamento do epitélio pigmentado vascularizado e um olho com osteoma de coroide), a rotura ocorreu em três olhos antes de quaisquer injeções. A mediana do número de injeções de ranibizumab após o diagnóstico da rotura do RPE foi de 3 (mínimo 2, máximo 5). Na visita de acompanhamento mais recente, não houve correlação estatisticamente significante entre o grau de RPE e logMAR de BCVA (p>0,05, r=0,112). Oito dos doze olhos tinham descolamento do epitélio pigmentado, desses, 7 olhos tinham PEDs com contornos irregulares antes da injeção. A altura média do PED foi 447 ± 122 µm. Conclusões: Nesta série, as roturas de epitélio pigmentado da retina aconteceram principalmente após a injeção intravítrea anti-VEGF para descolamento do epitélio pigmentado vascularizado. O aumento da altura vertical e contornos irregulares dos PEDs podem ser considerados fatores de risco para a formação da rotura ...

Aortic dissection during antiangiogenic therapy with sunitinib. A case report / Dissecção de aorta em terapia anti-angiogênica com sunitinibe. Um relato de caso

CONTEXT: Sunitinib is an antiangiogenic drug that has been approved for treating metastatic renal cancer. Its action as a tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs) and other angiogenesis receptors may lead to adverse effects such as hypertension and heart failure. However, reports in the literature on an association between sunitinib therapy and acute aortic dissection are rare. CASE REPORT: We report the case of a 68-year-old man with metastatic renal carcinoma who developed acute aortic dissection during sunitinib therapy. He had no history of hypertension or any other risk factor for aortic dissection. After aortic dissection had been diagnosed, sunitinib was withdrawn and an aortic endoprosthesis was placed. Afterwards, the patient was treated clinically with antihypertensive drugs and new therapy for renal cancer consisting of temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. CONCLUSION: Hypertension is a common event when antiangiogenic drugs are used in oncology. However, knowledge of other severe cardiovascular events that may occur in these patients, such as acute aortic dissection, is important. Adequate control over arterial pressure and frequent monitoring of patients during the first days of antiangiogenic therapy is essential for early diagnosis of possible adverse events. .

CONTEXTO: Sunitinibe é uma droga antiangiogênica aprovada para tratamento de câncer renal metastático. Sua ação como inibidor de tirosina quinase de receptores de fatores de crescimento do endotélio vascular (VEGFR) e de outros receptores de angiogênese pode levar a eventos adversos como hipertensão e insuficiência cardíaca. No entanto, é escassa na literatura a associação da terapia com sunitinibe e dissecção aguda de aorta. RELATO DE CASO: Relatamos o caso de um paciente do sexo masculino de 68 anos com câncer renal metastático que desenvolveu dissecção aguda de aorta durante tratamento com sunitinibe. O paciente não tinha histórico prévio de hipertensão nem outro fator de risco para dissecção de aorta. Após diagnóstico da dissecção de aorta, a droga foi suspensa e o paciente foi submetido à colocação de endoprótese na aorta, evoluindo posteriormente com controle clínico da pressão arterial e nova terapia para câncer renal com tensirolimo, um inibidor da via proteína alvo da rapamicina em mamíferos (mTOR). CONCLUSÕES: A hipertensão é um evento comum com uso de drogas antiangiogênicas na oncologia. No entanto, é importante o conhecimento de outros eventos cardiovasculares graves, como dissecção aguda de aorta, que podem ocorrer nesses pacientes. Controle adequado da pressão arterial e monitorização frequente dos pacientes nos primeiros dias de terapia antiangiogênica são essenciais para diagnóstico precoce de possíveis eventos graves. .

Onicólisis exudativa y paroniquia bacteriana aguda en relación con BIBF-1120 y paclitaxel: respuesta a la terapia tópica / Exudative onycholysis and acute bacterial paronychia related to BIBF-1120 and paclitaxel: response to topical therapy

Se presenta el caso de una paciente de 50 años de edad con cáncer de mama tratada con paclitaxel y BIBF 1120 semanal. La paciente desarrolló al final del duodécimo ciclo de quimioterapia una onicólisis distal, con exudado seroso intenso en el hiponiquio, dolor y mal olor en todas las uñas de las manos. Se trató con ácido fusídico tópico y aceponato de metilprednisolona al 1% dos veces al día, con una excelente respuesta desde los tres primeros días de tratamiento. A la semana de iniciar la terapia tópica, se observó una paroniquia bacteriana con la pérdida de la uña del quinto dedo de la mano izquierda, con cultivos positivos para Staphylococcus aureus sensible a meticilina. Hay pocos casos publicados de onicólisis exudativa asociada a quimioterapia. Sin embargo, están especialmente relacionados con paclitaxel. No se observaron recurrencias de las alteraciones ungueales semanas después de culminar la quimioterapia. Los corticoides tópicos y el ácido fusídico podrían ser considerados como una opción terapéutica cuando la onicólisis exudativa relacionada con paclitaxel esté establecida.

A case of a 50 years-old breast cancer patient treated with weekly paclitaxel and BIBF 1120 is reported herein. At the end of the twelfth cycle of chemotherapy, the patient developed distal onycholysis with intense hyponychium serous exudates, pain and malodor in all her fingernails. It was treated with topical fusidic acid and 1% methylprednisolone aceponate two times daily, with an excellent clinical response from the first three days of treatment. Bacterial paronychia with nail plate loss of the fifth left fingernail was observed a week after the topical therapy was started, with positive cultures for Methicillin susceptible Staphylococcus aureus. There are few reported cases of exudative onycholysis associated with chemotherapy. However, these are especially related to paclitaxel. No recurrences of nail disturbances were observed weeks after the end of chemotherapy. Topical corticosteroids and fusidic acid could be considered as a therapeutic option when exudative onycholysis related to paclitaxel is established.

Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab

OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes.

Hipertensión arterial como factor predictivo en pacientes con cáncer renal tratados con antiangiogénicos / Hypertension as predictive factor in renal cell cancer treated with antiangiogenic therapy

El conocimiento de las diversas vías de oncogénesis ha llevado al desarrollo en los últimos cinco años de nuevas terapias para el tratamiento del cáncer renal avanzado, las que poseen como blanco al factor derivado del endotelio vascular (VEGF) y sus receptores (antiangiogénicos) y al blanco mamífero de la rapamicina (mTOR). Los antiangiogénicos constituyen un grupo de moléculas activas con un espectro de toxicidad peculiar que comprende el desarrollo de hipertensión arterial, disfunción tiroidea y síndrome de mano-pie. La identificación de factores predictivos clínicos y moleculares lograría identificar aquellos pacientes que se beneficiarían con dicho tratamiento, evitando exposición y toxicidad innecesaria al resto. La aparición de hipertensión arterial se ha correlacionado con respuesta al tratamiento y eficacia clínica. En nuestra serie retrospectiva, los pacientes tratados con antiangiogénicos que desarrollaron hipertensión arterial tuvieron aumento de la tasa de respuestas e intervalo libre de enfermedad en comparación con aquellos que, tratados de la misma manera, no manifestaron hipertensión. La hipertensión arterial debería considerarse como un factor predictor clínico en su tratamiento. Dichos hallazgos deberían ser corroborados en forma prospectiva y con un mayor número de pacientes.

Knowledge of several pathways of oncogenesis has led to the development of novel therapies in the treatment of advanced kidney cancer in the last five years. These have targeted the vascular endothelium-derived factor (VEGF) (angiogenesis) and mammalian target of rapamycin (mTOR). Antiangiogenics are a group of active molecules with a peculiar spectrum of toxicity including the development of hypertension, thyroid dysfunction and hand-foot syndrome. The identification of molecular and clinical predictors would allow to identify those patients who would benefit from such treatment and saveguarding the rest from toxic exposure. The occurrence of hypertension has been correlated with treatment response and clinical efficacy. In our retrospective series, patients treated with antiangiogenic agents who developed high blood pressure showed a higher response rate and disease-free interval compared to those without increased blood pressure. Hypertension should be considered a clinical predictor in the treatment of these patients. These findings should be confirmed in a larger study population.

Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration.

Context: Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane (CNVM) secondary to age-related macular degeneration (AMD). Aims: To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD. Settings and Design: Prospective comparative case series carried out in an eye institute and eye department of a hospital in Kolkata, India. Materials and Methods: One hundred and four eyes with CNVM due to AMD were randomized into two groups. Group A (n=54; 24 occult) received monthly intravitreal ranibizumab injections (0.5 mg in 0.05 ml) and Group B (n=50; 22 occult) received monthly bevacizumab injections (1.25 mg in 0.05 ml) for 3 consecutive months and then as per study criteria. Data analysis done using SPSS software. P-value of <0.05 was considered statistically significant. Results: The mean best corrected visual acuity (BCVA) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 64 ETDRS letters at month 3 (P<0.001). In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 (P<0.001). At the end of 18 months, there was no statistically significant difference between groups A and B with respect to change in BCVA (P=0.563) or central macular thickness (CMT; P=0.281), as measured by optical coherence tomography (Stratus OCT 3000). No significant sight-threatening complications developed. Conclusions: Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD.

Síndrome de lisis tumoral en un paciente con cáncer de riñón tratado con sunitinib / Tumor lysis syndrome in a patient with a renal carcinoma treated with sunitinib

El síndrome de lisis tumoral (SLT) es un trastorno metabólico que ocurre como consecuencia de una destrucción celular masiva. Se caracteriza por la presencia de hiperuricemia, hiperfosfatemia, hipocalcemia e hiperkalemia, y predispone al desarrollo de insuficiencia renal aguda. En la mayoría de los casos el SLT ocurre luego de instaurarse un tratamiento antitumoral y es más frecuente en tumores de alto grado de malignidad y alta sensibilidad a la quimioterapia. Presentamos el caso de un paciente con diagnóstico de cáncer de riñón recidivado que presenta un SLT e insuficiencia renal aguda luego de iniciar tratamiento con sunitinib.

The tumor mor lysis syndrome (TLS) is a metabolic disorder resulting from a massive tumor breakdown. It is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia and hyperkalemia and predisposes to acute renal failure. TLS usually occurs after the initiation of cytotoxic therapy and is more frequent in the case of neoplasias with a high proliferative rate or that are highly chemo-sensitive. We report the case of a man with a recurrent kidney cancer who presented with a TLS and acute renal failure after initiation of sunitinib.