Preoperative co-application of bevacizumab and tissue plasminogen activator in vitrectomy for proliferative diabetic retinopathy

ABSTRACT Purpose: To investigate the clinical benefits of the co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy. Methods: Patients who underwent vitrectomy for proliferative dia-betic retinopathy complications were preoperatively given in-travitreal injection with either bevacizumab and tissue plasminogen activator (Group 1) or bevacizumab alone (Group 2). Primary outcomes were surgery time and number of intraoperative iatrogenic retinal breaks. Secondary outcomes included changes in the best-corrected visual acuity and postoperative complications at 3 months postoperatively. Results: The mean surgery time in Group 1 (52.95 ± 5.90 min) was significantly shorter than that in Group 2 (79.61 ± 12.63 min) (p<0.001). The mean number of iatrogenic retinal breaks was 0.50 ± 0.59 (0-2) in Group 1 and 2.00 ± 0.83 (0-3) in Group 2 (p<0.001). The best-corrected visual acuity significantly improved in both groups (p<0.001). One eye in each group developed retinal detachment. Conclusion: Preoperative co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy shortens the surgery time and reduces the number of intraoperative iatrogenic retinal breaks.

Refractive profile of children treated with intravitreal bevacizumab for retinopathy of prematurity

Purpose: To study the refractive profile of children after they received intravitreal injection of bevacizumab for retinopathy of prematurity (ROP). Methods: The study was conducted at a tertiary eye care hospital in South India. ROP patients of more than 1 year of age, presenting to the Pediatric Ophthalmology Clinic and Retina Clinic and having history of treatment for type ? ROP with intravitreal bevacizumab (IVB) or intravitreal bevacizumab and laser photocoagulation were included in the study. Cycloplegic refraction was done, and the refractive status was evaluated. The refractive status of age?matched, full?term children with uneventful perinatal and neonatal history was also recorded and compared to the study group. Results: Among 134 eyes of 67 study subjects, the major refractive error was myopia in 93 eyes (69.4%; spherical equivalent [SE] = ?2.89 ± 3.1, range = ?11.5 to ?0.5 D). There were 75 eyes (56%) with low?to?moderate myopia; high myopia was seen in 13.4%, emmetropia in 18.7%, and hypermetropia in 11.9% of eyes. The majority of them (87%) had with?the?rule (WTR) astigmatism. In 134 eyes, the SE was ?1.78 ± 3.2 (range = ?11.5 to 4 D); the SE of the 75 eyes with low?to?moderate myopia was ?1.53 ± 1.2 (range = ?0.50 to ?5 D). In the control group, the majority had emmetropia (91.8%). There was no significant association between the age at which IVB had been injected and the development of refractive errors (P = 0.078). The prevalence of low?to?moderate myopia was more than high myopia in patients with zone ? and zone ? ROP before treatment (60.0% and 54.5%, respectively). Conclusion: Myopia was the major refractive error seen in post?IVB pediatric patients. WTR astigmatism was more commonly seen. The age at which IVB injection had been given had no effect on the development of refractive errors

Bevacizumab effect on viability of free groin flaps in rats / Efeito do bevacizumabe na viabilidade de retalho inguinal livre em ratos

Introduction: Bevacizumab is among the most frequently used drugs in cancer treatment. There is evidence that some anti-angiogenic drugs reduce flap survival, but it is unclear whether this applies to Bevacizumab. We investigated the effect of Bevacizumab on the viability of free flaps in rats. Methods: The animals were randomly assigned to one of three groups. The Graft group received intravascular saline and was submitted to a full-thickness skin graft. The Flap-Saline and the Flap- BVZ groups underwent a free groin flap after receiving, respectively, intravascular saline solution or intravascular administration of Bevacizumab. Results: The Graft group showed a lower percentage of the viable area (22.81%) relative to the Flap- Saline (83.98%; p<0.0001) and the Flap-BVZ groups (60.50%; p=0.0048). The lowest vascular pedicle patency was observed in the Flap-BVZ group, but the difference relative to the Flap-Saline was not significant (arteries, p=0.0867; veins, p=0.9999). A significant difference was observed in the occurrence of necrosis (p=0.0010), which was higher in the histological samples of the Graft (87.50%) and the Flap- BVZ (60.00%) relative to the Flap-Saline Group (0%). Inflammation occurred less frequently in the Flap-Saline (33.33%) compared to the Graft (87.5%) and Flap- BVZ group (70.00%), but the difference did not reach significance (p=0.0588). No significant differences emerged in the occurrence of hemorrhage or intraluminal thrombosis. Conclusion: The increase in inflammation, decrease in patency and reduction of viable area, though not significant, are in line with the histological analysis and call for further research on the potential adverse effects of the drug.

Introdução: Bevacizumabe é um dos fármacos mais utilizados no tratamento do câncer. Existem evidências de que drogas antiangiogênicas reduzem a taxa de sobrevivência dos retalhos, porém não está claro se isso se aplica ao bevacizumabe. Investigamos o efeito de bevacizumabe na viabilidade de retalhos livres em ratos. Método: Os animais foram randomizados em três grupos. O grupo Enxerto recebeu injeção intravenosa de soro fisiológico 0,9% (SF 0,9%) e foi submetido a uma enxertia de pele total. Os grupos Retalho-SF e Retalho-BVZ foram submetidos a retalhos inguinais livres e receberam injeções intravenosas, respectivamente, de SF 0,9% e Bevacizumabe. Resultados: O grupo Enxerto apresentou menor percentual de área de retalho viável (22,81%) em relação ao grupo Retalho-SF (83,98%; p<0,0001) e Retalho-BVZ (60,50%; p=0,0048). Os pedículos do grupo Retalho-BVZ apresentaram menor patência, mas a diferença em relação ao grupo Retalho-SF não foi significante (artérias, p=0,0867; veias, p=0,9999). A ocorrência de necrose foi significativamente maior nos grupos Enxerto (87,50%) e Retalho-BVZ (60,00%) em relação ao grupo Retalho-SF (0%) (p=0,0010). A ocorrência de inflamação foi menor no grupo Retalho-SF (33,33%) em relação aos grupos Enxerto (87,5%) e Retalho-BVZ (70,00%), porém essa análise não atingiu significância (p=0,0588). Não houve diferenças significantes na ocorrência de hemorragia ou trombose intraluminal entre os grupos. Conclusão: O aumento da inflamação, redução da patência e das áreas viáveis dos retalhos, apesar de não significantes, corroboram com efeitos deletérios do bevacizumabe evidenciados na análise histológica e demandam futuros estudos dos potenciais efeitos adversos da droga.

Efficacy and safety analysis of intravitreal bio-similar products of bevacizumab in patients with macular edema because of retinal diseases

Purpose: The purpose of this study was to evaluate retrospectively the efficacy and safety profile of intravitreal injection of bevacizumab bio?similar product Zybev(Z) for macular edema because of retinal diseases. Methods: A retrospective analysis was conducted on patients with macular edema because of retinal diseases, who had been administered intravitreal injections of bio?similar bevacizumab at a tertiary eye care center. Changes in the retinal thickness and visual acuity were evaluated to judge the efficacy, and adverse events were noted for the safety profile over a period of 6 weeks. Results: A total of 104 patients were included in the study. The mean age of the patients was 53 ± 13.5 years. The mean pre?injection best corrected visual acuity (BCVA) was 1.32 ± 0.70 log minimum angle of resolution (logMAR) with a central subfield thickness (CST) of 429.26 ± 204.30 ?m, and the post?injection BCVA at 6 weeks was 1.13 ± 0.71 logMAR with a CST of 302.26 ± 104.50 ?m; this change was statistically significant (P < 0.05) for all groups. The mean average cube thickness (?m) decreased from 11.85 ± 1.96 pre?injection to 10.52 ± 1.75 post?injection, and the mean average cube volume (mm3) decreased from 329.30 ± 54.35 to 302.23 ± 49.56 (P < 0.05). During the follow?up period after injection, no patient had inflammation, endophthalmitis, an increase in intra?ocular pressure, or systemic side effects. Conclusion: This short?term retrospective analysis provides evidence regarding the efficacy and safety of intravitreal injection of bio?similar products of bevacizumab for the treatment of macular edema because of retinal diseases

Staphylococcus hominis: a rare cause of endophthalmitis / Staphylococcus hominis: uma causa rara de endoftalmite

ABSTRACT Staphylococcus hominis (S. hominis) is a coagulase-negative Staphylococci and an infrequent cause of endophthalmitis. Due to its ability to produce biofilm, especially in diabetic patients, strains may acquire antibiotic resistance. We present two cases of S. hominis endophthalmitis, one with acute endophthalmitis after intravitreal bevacizumab injection and one with chronic endophthalmitis following undiagnosed penetrating ocular trauma. Although there are only four published S. hominis endophthalmitis cases in the literature, to the best of our knowledge, there has been no previously published case after intravitreal bevacizumab.

RESUMO Staphylococcus hominis (S. hominis) é um estafilococo coagulase-negativo e uma causa pouco frequente de endoftalmite. Devido à sua capacidade de produzir biofilme, especialmente em pacientes diabéticos, cepas dessa bactéria podem adquirir resistência a antibióticos. Este relato apresenta dois casos de endoftalmite por S. hominis: um de endoftalmite aguda após injeção intravítrea de bevacizumabe e outro de endoftalmite crônica após trauma ocular penetrante não diagnosticado. Embora existam apenas quatro casos de endoftalmite por S. hominis publicados na literatura, até onde sabemos não houve nenhum caso publicado anteriormente após bevacizumabe intravítreo.

Prospective evaluation of the effectiveness of combined treatment of macular edema secondary to retinal vein occlusion with intravitreal bevacizumab and dexamethasone implants / Estudo intervencionista prospectivo para avaliar a eficácia da associação do bevacizumabe intravítreo ao implante de dexametasona para edema macular secundário à oclusão da veia retiniana

ABSTRACT Purpose: To evaluate the effectiveness of in­­­travitreal bevacizumab injections following a single dexamethasone implant in the treatment of macular edema secondary to branch and central retinal vein occlusion. Methods: This was a prospective interventional non-comparative study, 44 eyes of patients with naïve macular edema related to branch and central retinal vein occlusion were treated with a dexamethasone implant. Patients were followed-up at four-week intervals from the second to the sixth month. If persistent or recurrent macular edema occurred during this period, the patient was treated with intravitreal bevacizumab injections on an as-needed basis. The outcome measures were best-corrected visual acuity and central macular thickness changes. Results: The mean best-corrected visual acuity changed from 0.97 ± 0.33 LogMAR at baseline to 0.54 ± 0.40 at the six-month post-implant examination (p<0.00001). Improvement ≥3 Snellen lines were seen in 20 eyes (45.54%). The mean central macular thickness at baseline was 670.25 ± 209.9 microns. This had decreased to 317.43 ± 112.68 microns at the six-month follow-up (p<0.00001). The mean number of intravitreal bevacizumab injections received in the six months post-implant was 2.32. The mean time from dexamethasone implant to first anti-VEGF injection was 3.45 months. Conclusions: Intravitreal bevacizumab injections following a single dexamethasone implant were found to improve best-corrected visual acuity and central macular thickness in patients with macular edema due to branch and central retinal vein occlusion at six months, with few intravitreal injections required.

RESUMO Objetivo: Avaliar a eficácia da combinação de in­jeções intravítreas de bevacizumabe em olhos com edema macular secundário à oclusão de ramo e da veia central da retina após um único implante de dexametasona. Métodos: Foi realizado um estudo prospectivo intervencionista não comparativo com 44 olhos de pacientes com edema macular relacionado à oclusão de ramo e veia central da retina, sem tratamento prévio e tratados com um único implante de dexametasona, que foram acompanhados em intervalos de quatro semanas do segundo ao sexto mês. Se fosse constatado edema macular persistente ou recorrente durante esse período, os pacientes eram tratados com injeções intravítreas de bevacizumabe em um regime ajustado conforme a necessidade. Foram estudadas a melhor acuidade visual corrigida e alterações da espessura macular central. Resultados: A média da melhor acuidade visual corrigida mudou de 0,97 ± 0,33 LogMAR iniciais para 0,54 ± 0,40 no exame de 6 meses (p<0,00001). Vinte olhos (45,54%) melhoraram 3 linhas de Snellen ou mais. A média da espessura macular central inicial foi de 670,25 ± 209,9 μm e diminuiu para 317,43 ± 112,68 μm na visita de 6 meses (p<0,00001). O número médio de injeções intravítreas de bevacizumabe em 6 meses foi de 2,32 e o tempo médio entre o implante de dexametasona e a primeira injeção de anti-VEGF foi de 3,45 meses. Conclusão: Injeções intravítreas de bevacizumabe após um único implante de dexametasona podem proporcionar um aumento da melhor acuidade visual corrigida e diminuição da espessura macular central aos 6 meses em pacientes com edema macular devido à oclusão de ramo e da veia central da retina, com poucas injeções intravítreas.

99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

Clinical efficacy of paclitaxel and carboplatin with versus without bevacizumab in treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC). Methods    The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis. Results    Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial  group than those in the control group. Conclusion    For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.

Clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer / 中国医师进修杂志

Objective:To compare the clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer.Methods:The clinical data of 68 patients with advanced colorectal cancer from January 2018 to December 2020 in Baotou Tumor Hospital were retrospectively analyzed. Among them, 40 patients with treated with bevacizumab combined with chemotherapy (bevacizumab group), 28 patients were treated with cetuximab combined with chemotherapy (cetuximab group), and the chemotherapy of two group was FOLFOX/FOLFIRI program. The short-term clinical efficacy, adverse reactions and pharmacoeconomic evaluation result were compared between two groups.Results:There were no statistical differences in effective rate and disease control rate between bevacizumab group and cetuximab group: 30.00% (12/40) vs. 28.57% (8/28) and 67.5% (27/40) vs. 60.71% (17/28), P>0.05. The incidence of Ⅲ to Ⅳ grade erythra in bevacizumab group was significantly lower than that in cetuximab group: 2.50% (1/40) vs. 71.43% (20/28), and there was statistical difference ( P<0.01); there were no statistical differences in the incidences of Ⅲ to Ⅳ grade bone marrow suppression, nausea vomiting, hepatic functional lesion and diarrhea between two groups ( P>0.05). The pharmacoeconomic evaluation result showed that the cost of monoclonal antibody and total cost in bevacizumab group were significantly lower than those in cetuximab group: (9 009 ± 1 500) yuan vs. (27 840 ± 2 202) yuan and (11 242 ± 1 731) yuan vs. (29 867 ± 3 002) yuan, and there were statistical differences ( P<0.01); the cost-effectiveness ratio in bevacizumab group was 37 473.3, and it in cetuximab group was 104 430.1, the incremental cost-effectiveness ratio of two programs was 11 640.6. Conclusions:In the treatment of advanced colorectal cancer, the efficacy of bevacizumab combined with chemotherapy is similar to that of cetuximab combined with chemotherapy, but bevacizumab combined with chemotherapy has lower costs and fewer adverse reactions, so bevacizumab is more economical and applicable.

Initial Treatment of Aumolertinib in Combination with Bevacizumab for Advanced NSCLC with Primary EGFR T790M Mutation: A Report of Three Cases and Literature Review / 中国肺癌杂志

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
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Quantitative assessment of silicone oil release with siliconized and silicone oil-free syringes by microflow imaging microscopy / Avaliação quantitativa da liberação de óleo de silicone por seringas siliconizadas e sem óleo de silicone usando microflow imaging microscopy

ABSTRACT Purpose: Since particles are released in syringes during intravitreal injections, we assessed them quantitatively after agitating syringes commonly used for intravitreal injections. Methods: With and without agitation, the SR 1-ml insulin, Becton-Dickinson Ultra-Fine 0.3-ml Short Needle with a half-unit scale, HSW Norm-Ject Tuberculin, and Becton-Di­ckinson 1-ml Luer Lok Tip were examined with buffer and bevacizumab, aflibercept, and ziv-aflibercept. Flow imaging microscopy was performed to assess the particle numbers, concentrations, morphology, and size distribution. Results: Using the Becton-Dickinson Ultra-Fine syringe, the average particle count after agitation was higher than in the no-agitation group. For particles greater than 10 and 25 µm, differences were observed using the SR syringe between the two studied conditions. There were no significant differences in the means for the other syringes. Without agitation, the SR syringe had the highest number of particles (2,417,361.7 ± 3,421,575.5) followed by the Becton-Dickinson Ultra-Fine with 812.530,9 ± 996.187,2. The Becton-Dickinson Luer Lok Tip and HSW Norm-Ject performed equally with 398,396.8 ± 484,239.2 and 416,016.4 ± 242,650.1 particles, respectively. Conclusions: Flicking syringes to eliminate air bubbles results in increased numbers of particles released during intravitreal injections into the human vitreous.

RESUMO Objetivo: Visto que partículas são liberadas nas seringas durante as injeções intravítreas (IVIs), estas foram avaliadas quantitativamente após a agitação das seringas mais comumente usadas para injeções intravítreas. Métodos: A seringa SR de 1 ml de insulina, a agulha curta Becton-Dickinson Ultra-Fine 0,3 ml com escala de meia unidade, HSW Norm-Ject Tuberculin e a Becton-Dickinson Luer Lok Tip de 1 ml foram estudadas com placedo e com bevacizumabe, aflibercept e ziv-aflibercept, com e sem agitação. MicroFlow Imaging Mi­croscopy foi realizada para avaliar o número de partículas, con­centração, morfologia e distribuição das mesmas por tamanho. Resultados: A contagem média de partículas após agitação foi maior do que no grupo sem agitação usando a seringa Becton-Di­ckinson Ultra-Fine. Diferenças foram observadas usando a seringa SR entre as duas condições estudadas para partículas maiores que 10 e 25 µm. Para as demais seringas, não foram observadas diferenças significativas nas médias. A seringa SR apresentou o maior número de partículas sem agitação (2.417.361,7 ± 3.421.575,5) seguida da Becton-Dickinson Ultra-Fine com 812.530,9 ± 996.187,2. A BD Luer Lok Tip e a HSW Norm-Ject se comportaram de forma semelhante com 398.396,8 ± 484.239,2 e 416.016,4 ± 242.650,1 partículas, respectivamente. Conclusões: Agitar seringas para remover bolhas de ar resulta em um maior número de partículas liberadas durante Becton-Dickinson no vítreo humano.

Retinopatía de la prematuridad agresiva posterior / Aggressive Posterior Retinopathy of Prematurity

Introducción: La retinopatía del prematuro es una enfermedad ocular provocada por una alteración en la vasculogénesis de la retina, que lleva a la pérdida parcial o total de la visión. Objetivo: Presentar el primer caso, en la provincia de Santa Clara, de retinopatía de la prematuridad agresiva posterior y el tratamiento realizado. Presentación del caso: Niña prematura con más de 5 factores de riesgo al nacer que presentó retinopatía de la prematuridad agresiva posterior y se le realizó tratamiento con bevacizumab intravítreo. Conclusiones: La evolución de la niña en un período de un 1 año resultó satisfactoria con regresión total de la enfermedad. El tratamiento establecido constituye un método alternativo con buenos resultados en algunas condiciones específicas como la retinopatía del prematuro agresiva posterior(AU)

Introduction: Retinopathy of prematurity is an ocular disease caused by an alteration in retinal vasculogenesis, leading to partial or total loss of sight. Objective: To present the first case, in the province of Santa Clara, of aggressive posterior retinopathy of prematurity and the treatment performed. Case presentation: Premature girl with more than 5 risk factors at birth who presented aggressive posterior retinopathy of prematurity and was treated with intravitreal bevacizumab. Conclusions: The evolution of the girl in a period of 1 year was satisfactory with total regression of the disease. The established treatment constitutes an alternative method with good results in some specific conditions such as aggressive posterior retinopathy of prematurity(AU)

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.

Efficacy of Bevacizumab Combined with Paclitaxel and Platinum-Based Chemotherapy in Advanced Metastatic Cervical Cancer and Its Effect on T Lymphocyte Subsets and Tumor Markers / 肿瘤防治研究

Objective To investigate the efficacy of bevacizumab combined with paclitaxel and platinum-based chemotherapy in advanced metastatic cervical cancer and its effect on T lymphocyte subsets and tumor markers. Methods Sixty patients with advanced metastatic cervical cancer (treated in our hospital) were randomly divided into control (30 cases) and treatment (30 cases) groups. All patients were given radiotherapy; the control group received paclitaxel and platinum-based chemotherapy, whereas the treatment group received the same with added bevacizumab. The pain conditions (visual analog score (VAS)) and quality of life (Karl Fischer quality of life (KPS)), clinical efficacy, T lymphocyte subset levels (CD3+, CD4+, and CD8+), tumor markers (carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and squamous epithelial carcinoma-associated antigen (SCCA)) and adverse reactions were compared between the two groups. Results The VAS score, serum CA125, CEA, SCCA, and CD8+ level were significantly reduced in both groups after treatment (P < 0.05), and it significantly decreased in the treatment group compared with the control group (P < 0.05). KPS score, CD3+, and CD4+ levels significantly increased after treatment in the two groups (P < 0.05), and compared with the control group, the treatment group significantly increased (P < 0.05). Moreover, the total effective rate (66.67%) was significantly higher than that in the control group (40.00%) (P < 0.05), and no significant difference existed in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Bevacizumab combined with paclitaxel and platinum-based chemotherapy can effectively reduce the pain and improve the immune function and quality of life of patients with advanced metastatic cervical cancer. This chemotherapy is also safe and effective.

Clinical observation of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of EGFR-TKI acquired resistant advanced lung adenocarcinoma / 中国药房

OBJECTIVE To compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） acquired resistant advanced lung adenocarcinoma. METHODS The information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group （32 cases）， anlotinib combined chemotherapy group （24 cases） and bevacizumab combined chemotherapy group （28 cases）. Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection， and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy， patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally， once a day， for 14 consecutive days and 7 days of discontinuation， based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy， based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles， with one cycle every three weeks. The overall response rate （ORR）， disease control rate （DCR）， median progression-free survival （mPFS）， and the changes of serum tumor markers were compared among three groups before and after treatment； meanwhile， the occurrence of adverse drug reactions was recorded， and the 1-year survival rate was followed up. RESULTS After 4 treatment cycles， ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group （P＜0.05）； mPFS of the two groups were significantly longer than chemotherapy group， and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group （P＜0.05）. After 4 treatment cycles， the serum levels of tumor markers in three groups were significantly lower than before treatment， and both combined chemotherapy groups were significantly lower than chemotherapy group （P＜0.05）. There was no statistically significant difference in the incidence of adverse reactions such as nausea， vomiting， bone marrow suppression， and 1-year survival rate among the three groups of patients （P＞0.05）. CONCLUSIONS Bevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.

Clinical observation on osimertinib combined with bevacizumab in treatment of advanced non-small cell lung cancer with epidermal growth factor receptor T790M positive / 肿瘤研究与临床

Objective:To explore the clinical effect of osimertinib combined with bevacizumab in treatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) T790M positive.Methods:A prospective study was conducted on 83 EGFR T790M-positive advanced NSCLC patients who were admitted to Anhui Chest Hospital from April 2018 to December 2020. The patients were randomly divided into the observation group and the control group using random number table method. Among them, 41 cases in the control group were treated with osimertinib, while 42 cases in the observation group were treated with osimertinib combined with bevacizumab. The clinical efficacy, tumor markers [carcinoembryonic antigen (CEA), serum neuron specific enolase (NSE)] levels, tumor vascular associated protein factor (S100β protein) level and adverse reactions between the two groups after 3 months of treatment were compared. Kaplan-Meier method was used to draw survival curves, and the 1-year survival status of patients in the two groups was compared.Results:The disease control rate in the observation group was 69.05% (29/42), which was higher than that in the control group [43.90% (18/41)] ( χ2 = 5.34, P = 0.021), but there was no statistical difference in the objective response rate between the two groups [33.33% (14/42) vs. 21.95% (9/41)] ( χ2 = 1.34, P = 0.247). After treatment, the serum levels of CEA [(19.9±3.6) μg/ml vs. (79.3±7.9) μg/ml, (27.8±4.8) μg/ml vs. (78.6±8.1) μg/ml] and NSE [(18.9±3.2) ng/ml vs. (27.2±5.0) ng/ml, (22.0±3.3) ng/ml vs. (26.1±4.8) ng/ml] in the observation group and control group were lower than those before treatment (all P < 0.05). There was no statistical difference in CEA and NSE levels between the two groups before treatment (both P > 0.05), and after treatment, the observation group was lower than the control group (both P < 0.001). The serum S100β levels of patients in the observation and control groups after treatment were all higher than those before treatment [(50±5) μg/ml vs.(44±5) μg/ml, (55±4) μg/ml vs. (45±6) μg/ml, both P = 0.001), and the difference in S100β level between the two groups before treatment was not statistically significant ( P > 0.05), and after treatment, the observation group was lower than the control group ( P < 0.001). Both groups of patients did not experience acute severe adverse reactions during the medication period. There were no statistical differences between the observation group and the control group in the incidence rates of nausea and vomiting [9.52% (4/42) vs. 7.32% (3/41)], constipation and diarrhea [4.76% (2/42) vs. 4.88% (2/41)], thrombocytopenia [9.52% (4/42) vs. 4.88% (2/41)], and liver function damage [7.14% (3/42) vs. 2.44% (1/41)] (all P > 0.05). The 1-year overall survival rate of the observation group was higher than that of the control group [68.3% (95% CI 47.9%-86.1%) vs. 41.0% (95% CI 22.4%-65.3%)], and the overall survival of the observation group was better than that of the control group ( χ2 = 2.60, P = 0.037). Conclusions:The combination of osimertinib and bevacizumab in treatment of EGFR T790M-positive advanced NSCLC can effectively regulate the levels of tumor related factors, with good efficacy and safety.

Morphological and functional retinal changes in neovascular age-related macular degeneration treated with intravitreal bevacizumab

Purpose: This study was conducted to determine the morphological and functional retinal changes in patients with neovascular age?related macular degeneration (nAMD) treated with intravitreal bevacizumab 1.25 mg. Methods: This was a prospective, nonrandomized, interventional study. Eighteen eyes of 18 subjects with nAMD were treated with intravitreal bevacizumab (1.25 mg) injection. Subjects underwent complete ophthalmic evaluation which included visual acuity, slitlamp examination, tonometry, binocular ophthalmoscopy, optical coherence tomography (OCT), and MP1 microperimetry before the intravitreal injection and the follow?up at 1 and 3 months. Test of significance such as Chi?squared test, paired ttest and oneway analysis of variance (ANOVA) linear trend were used to compare the pre? and post?anti?VEGF outcomes. Intraclass correlation was done to assess the intra observer variability. Results: Mean retinal sensitivity had increased from 3.77 ± 3.13 dB at baseline to 4.93 ± 2.42 dB at 3 months (P = 0.05). Visual acuity improved from 0.62 ± 0.36 at baseline to 0.52 ± 0.36 at 1 month and 0.48 ± 0.34 at 3?month followup, but overall change was not significant (P = 0.40). There was a significant reduction in central foveal thickness (CFT) from 274.61 ± 117.95 at baseline to 179.83 ± 84.18 at 1 month and 179.00 ± 126.55 at 3?month follow?up (P = 0.013). Conclusion: Intravitreal bevacizumab (1.25 mg) injection in nAMD improves retinal function, quantified by retinal sensitivity, scotoma characteristics, fixation stability by MP 1 microperimetry and morphological parameters quantified by CFT in SDOCT. These changes show the effectiveness of treatment with intravitreal bevacizumab in nAMD

Calidad de vida según función visual en degeneración macular húmeda asociada a la edad tratada con Bevacizumab / Quality of Life According to Visual Function in Age-related Wet Macular Degeneration Treated with Bevacizumab

Introducción: La degeneración macular asociada a la edad, es causa frecuente de ceguera o baja visión en el adulto mayor. La valoración de la calidad de vida relativa a la función visual, es fundamental en estos pacientes tratados con Bevacizumab. Objetivo: Evaluar la calidad de vida en relación con la función visual en pacientes con degeneración macular tratada con Bevacizumab asociada a la edad. Métodos: Estudio descriptivo longitudinal prospectivo realizado en el ICO "Ramón Pando Ferrer", desde enero de 2019 hasta mayo de 2021. La muestra fue de 52 pacientes. El cuestionario NEI VFQ-25 fue aplicado antes y después de la administración de las tres dosis del medicamento intravítreo. Resultados: Predominó el sexo femenino, el grupo etario de mayor representación fue el de 60 a 79 años, la enfermedad sistémica más frecuente fue la hipertensión y ocular, la catarata. Casi todos los pacientes ganaron más de dos líneas en la cartilla de Snellen, el 42,3 por ciento presentó una ganancia de 3 líneas o más. El resultado de la mayoría de los elementos que explora el test, así como la función visual total es significativo desde el punto de vista estadístico. Conclusiones: Hubo una mejoría en la calidad de vida relativa a la función visual en los pacientes después de ser tratados con Bevacizumab. No existió una relación directamente proporcional entre la mejor agudeza visual post tratamiento y la mejora de la función visual total(AU)

Introduction: Age-related macular degeneration constitutes a frequent cause of blindness or low vision in the older adult. The assessment of quality of life related to visual function is essential in these patients treated with Bevacizumab. Objective: To assess the quality of life in relation to visual function in patients with age-related macular degeneration treated with Bevacizumab, at the ICO "Ramón Pando Ferrer", from January 2019 to May 2021. Methods: Prospective longitudinal descriptive study. The sample was 52 patients and the NEI VFQ-25 questionnaire was applied before and after three doses of the intravitreal drug. Results: Female gender predominated, the most represented age group was 60 to 79 years, the most frequent systemic disease was hypertension and the most frequent ocular disease was cataract. Almost all patients gained more than two lines in the Snellen chart, 42.3 percent presented a gain of 3 lines or more. The result of most of the items explored by the test, as well as the total visual function is statistically significant. Conclusions: There was an improvement in quality of life relative to visual function in patients after being treated with Bevacizumab. There was no directly proportional relationship between improved post-treatment visual acuity and improvement in total visual function(AU)

Relationship between refractive outcomes and quantitative retinal vascularization and severity of plus disease in eyes treated with intravitreal bevacizumab

Purpose: The study aimed to investigate the relationship between refractive outcomes with the extent of retinal vascularization and severity of the plus disease in infants treated with intravitreal bevacizumab (IVB). Methods: Pre?IVB fundus images (PFIs), final fundus images (FFIs), and refractive outcomes of the 93 infants who underwent IVB monotherapy for type 1 and aggressive retinopathy of prematurity (A?ROP) were retrospectively evaluated. Quantitative measurements were performed on PFIs and FFIs. Pre?IVB plus severity was scored on a five?leveled scale. Correlation between spherical equivalent (SE) with pre?treatment and final extent of the temporal retinal vascularization and pre?treatment severity of plus disease was analyzed. Results: There was a linear and low positive correlation between the extent of pre?IVB and final temporal retinal vascularization with final SE (p = 0.000, r = 0.267; P = 0.002, r = 0.274, respectively). There was a low negative correlation between the pre?IVB plus severity score with final SE (p = 0.012, r = ?0.192). Gestational age (GA), birth weight (BW), IVB dose, presence of additional IVB, or laser treatments were not correlated with refractive outcome. Out of 171 eyes, 38 eyes had >1 D myopia. In the univariate logistic analyses, pre?IVB retinal zone and pre?IVB and final extent of the temporal retinal vascularization were found to be related to the development of >1 D myopia (p = 0.002, odds ratio (OR) = 0.298; P = 0.000, OR = 0.281; P = 0.001, OR = 0.317; respectively). Conclusion: Our study indicates that the pre?treatment and final extent of retinal vascularization were the main parameters that were related to final refractive outcomes in IVB?treated eyes for type 1 and A?ROP.