Reconstrucción palpebral tras resección tumoral del globo ocular / Palpebral Reconstruction after Tumor Resection of the Eyeball

Los defectos palpebrales creados tras la resección tumoral pueden ser parciales o totales, afectar a la lamela externa, a la interna o a ambas y requerir diferente técnica reconstructiva, simple o compleja. El objetivo es presentar los resultados cosméticos y funcionales en una paciente que se le realzó una técnica combinada para resolver un problema complejo del aparato palpebral después de una enucleación. Se logró un aparato palpebral armónico, en el que sus estructuras tienen orden, funcionabilidad y simetría con el lado contralateral. La reconstrucción de los defectos complejos del aparato palpebral solo es posible con la combinación de varias técnicas. Se logró armonía, simetría contralateral y orden de las estructuras(AU)

The palpebral defects created after tumor resection can be partial or total, affect the external lamella, the internal lamella or both, and require different reconstructive techniques, simple or complex. The objective is to present the cosmetic and functional results in a patient who underwent a combined technique to solve a complex problem of the palpebral apparatus after enucleation. A harmonic palpebral apparatus was achieved, in which its structures have order, functionality and symmetry with the contralateral side. The reconstruction of complex defects of the palpebral apparatus is only possible with the combination of several techniques. Harmony, contralateral symmetry and order of the structures were achieved(AU)

Terapia combinada para el tratamiento de la lumbalgia / Combination therapy for the treatment of low back pain

Introducción: El dolor lumbar es una de las afecciones que causa mayor índice de incapacidad, por lo que se ha señalado como una de las principales causas de invalidez laboral temporal o definitiva. Objetivo: Identificar las ventajas de la aplicación de ozono médico como terapia combinada en el tratamiento de pacientes con lumbalgia aguda. Métodos: Se realizó un estudio experimental de casos y controles donde cada grupo estuvo integrado por 50 pacientes mayores de 20 años de edad con diagnóstico de dolor lumbar, previo consentimiento informado. El grupo control recibió tratamiento con esquemas terapéuticos tradicionales según los consensos internacionales para el tratamiento del dolor lumbar agudo. En el caso de los pacientes del grupo de casos se adicionó ozono médico en tres sesiones semanales por vía rectal hasta completar 10 sesiones. Se utilizó la prueba de comparación de medias y de McNemar para identificar cambios en la intensidad del dolor y en la presencia y tipo de incapacidad. Resultados: Hubo un promedio de edad por encima de los 50 años, con predominio de pacientes femeninas. La intensidad del dolor al inicio del tratamiento se comportó como media de ambos grupos en 8,76 puntos, mientras que el 87 por ciento de los pacientes refirió algún tipo de discapacidad. Predominó la incapacidad moderada. Conclusiones: La aplicación de ozono médico combinado influyó positivamente en la disminución de la intensidad del dolor y en la presencia y tipo de incapacidad(AU)

Introduction: Low back pain is one of the conditions that generates the highest rate of disability, has been identified as one of the main causes of temporary and / or permanent work disability. Objective: To identify the advantages of the application of medical ozone as a combined therapy in the treatment of patients with acute low back pain. Methods: An experimental case-control study was carried out where each group consisted of 50 patients over 20 years of age with a diagnosis of low back pain. The control group received treatment with traditional therapeutic schemes according to international consensus for the treatment of acute low back pain, in the case of patients in the case group the use of medical ozone was added, in three weekly sessions rectally until completing 10 sessions. The comparison test of means and McNemar were used to identify changes in pain intensity and in the presence and type of disability. Results: Average age above 50 years with a predominance of female patients. The intensity of pain at the start of treatment behaved as an average of both groups at 8.76 points, while 87 percent of the patients reported some type of disability with a predominance of moderate disability. Conclusions: The application of combined medical ozone positively influenced the decrease in pain intensity and the presence and type of disability(AU)

Research progress of conversion therapy in colorectal cancer liver metastases / 中华胃肠外科杂志

The probability of developing liver metastases in patients with colorectal cancer is 40%-50%. Liver metastases remain an important adverse factor affecting long-term prognosis of colorectal cancer patients. Surgical resection of liver metastases is the only potentially curative treatment option. After comprehensive treatment, initially unresectable liver metastases might be converted to resectable tumors. This concept is known as conversion therapy. In this review, research status of conversion therapy in colorectal cancer liver metastases was summarized, providing updated concept of resectability, discussions on the assessment of tumor response and timing of operation, debates on the influence on tumor sidedness, and latest advancement in the treatment strategy of conversion therapy. Through analyzing existing problems, we hope to offer insights into possible progress in the future and provide references for the development of clinical practice.

Analgesia multimodal una alternativa para el paciente quirúrgico / Multimodal analgesia: an alternative for the surgical patient

Introducción: El dolor posterior a una intervención quirúrgica, es un síntoma frecuentemente observado, no cumple una función útil y el peligro de no tratarlo aumenta la morbilidad y mortalidad posoperatoria. Objetivo: Destacar la importancia de la analgesia multimodal en el control del dolor agudo posoperatorio. Métodos: Revisión en la literatura impresa tanto nacional como internacional, sobre la analgesia y la modalidad multimodal y además, se hizo búsqueda en Internet. En los artículos revisados se obtuvieron distintos aspectos clínicos de la analgesia multimodal y de sus protocolos. Resultados: En la actualidad para mitigar el dolor y alcanzar la máxima expresión en la analgesia posoperatoria se han desarrollado diferentes modalidades analgésicas, aunque de todas ellas solo ha alcanzado mayor grado de recomendación, la analgesia multimodal porque es capaz de conseguir con su efecto sinérgico y con pequeñas dosis, una mejor potencia para producir analgesia y menos efectos adversos. Consideraciones finales: La analgesia multimodal logra un control adecuado del dolor agudo posoperatorio, disminuye las complicaciones posoperatorias y la necesidad de analgesia de rescate, pero todo esto depende del protocolo de analgesia multimodal propuesto, la vía de administración de los fármacos elegidos, sus dosis y el cumplimiento de los intervalos de aplicación(AU)

Introduction: The pain after surgery is a frequently observed symptom, it is not a useful function and the danger of not treating it increases postoperative morbidity and mortality. Objective: To highlight the importance of multimodal analgesia in the control of acute postoperative pain. Methods: It was made a review in the printed literature both national and international on the multimodal analgesia, and in addition, a search in Internet. In the reviewed articles there were obtained different clinical aspects of multimodal analgesia and its protocolization. Results: Nowadays, in order to mitigate the pain and achieve the maximum expression in the postoperative analgesia, there have been developed different analgesic modalities, although of all of them it only has achieved a greater degree of recommendation, the multimodal analgesia because it is capable of achieving with its synergetic effect and with small doses, a better power to produce analgesia and fewer adverse effects. Conclusions: The multimodal analgesia achieved adequate control of acute postoperative pain, decreasing the inherent complications of this state and the need of rescue analgesia. All of the above depends on the proposed protocol of multimodal analgesia, the route of administration of the chosen drugs, their doses and the compliance of the application intervals(AU)

Facotrabeculectomía por dos vías como tratamiento combinado de pacientes con glaucoma y catarata / Two-site phacotrabeculectomy as combined therapy for patients with glaucoma and cataract

RESUMEN Objetivo: Determinar los resultados de la facotrabeculectomía por dos vías como tratamiento combinado de pacientes cubanos con glaucoma y catarata. Métodos: Se realizó un estudio observacional descriptivo longitudinal prospectivo en pacientes adultos cubanos tratados con facotrabeculectomía en el Servicio de Glaucoma del Instituto Cubano de Oftalmología "Ramón Pando Ferrer" entre junio del año 2016 y abril de 2017. El universo estuvo constituido por todos los pacientes operados con facotrabeculectomía por dos vías. La muestra la integraron pacientes operados por un mismo cirujano, quienes estuvieron de acuerdo con participar en la investigación. Se excluyeron aquellos con cirugía intraocular previa. Salieron del estudio los que no pudieron mantener el seguimiento en la institución. Se estudiaron las variables edad, sexo, color de la piel, agudeza visual mejor corregida, presión intraocular, número de medicamentos hipotensores oculares y complicaciones presentadas. El seguimiento fue por dos años con consultas al día siguiente, a los siete y a los treinta días; a los tres y a los seis meses; al año y a los dos años. Resultados: Se observaron 31 pacientes. La edad promedio fue de 70 años, con predominio del sexo femenino y el color de la piel no blanco; la agudeza visual mejor corregida preoperatoria media 0,58 y la posoperatoria 0,73. La presión intraocular media preoperatoria 22,04 mmHg y a los dos años 16,37 mmHg. La media de los medicamentos hipotensores preoperatorios fue 3,0 y 0,3 a los dos años. Las complicaciones más frecuentes resultaron la ruptura transquirúrgica de la cápsula posterior y la opacidad posquirúrgica de la cápsula posterior. Conclusiones: Con la facotrabeculectomía por dos vías disminuye la presión intraocular; mejora la agudeza visual mejor corregida y se reduce el número de fármacos hipotensores oculares al menos durante dos años. Las complicaciones asociadas a la técnica son mínimas(AU)

ABSTRACT Objective: Determine the results of two-site phacotrabeculectomy as combined therapy for Cuban patients with glaucoma and cataract. Methods: An observational prospective longitudinal descriptive study was conducted of Cuban patients undergoing phacotrabeculectomy at the Glaucoma Service of Ramón Pando Ferrer Cuban Institute of Ophthalmology from June 2016 to April 2017. The study universe was all the patients undergoing two-site phacotrabeculectomy. The sample was patients operated on by the same surgeon who consented to participate in the research. Patients with a history of intraocular surgery were excluded, as well as those who could not be followed up at the institution. The variables considered were age, sex, skin color, best corrected visual acuity, intraocular pressure, number of ocular hypotensive drugs, and complications developed. Follow-up extended for two years with visits on the next day, at seven and thirty days, at three and six months, and at one and two years. Results: Thirty-one patients were observed. Mean age was 70 years, with a predominance of the female sex and non-white skin color. Best corrected visual acuity was 0.58 preoperative and 0.73 postoperative. Mean preoperative intraocular pressure was 22.04 mmHg, whereas at two years it was 16.37 mmHg. Hypotensive drugs averaged 3.0 preoperative and 0.3 at two years. The most common complications were intraoperative posterior capsule rupture and postsurgical posterior capsule opacity. Conclusions: Two-site phacotrabeculectomy reduces intraocular pressure, improves best corrected visual acuity and lowers the number of ocular hypotensive drugs for at least two years. The complications associated to the technique are minimum(AU)

Impact of brief intervention and art therapy for alcohol users / Impacto de la intervención breve y de la arteterapia en usuarios de alcohol / Impacto da intervenção breve e arteterapia para usuários de álcool

ABSTRACT Objective: To identify the impact of brief intervention paired with art therapy in patients who use alcohol. Method: This study presents intra-group design, with 11 alcoholics in the city of Tamarana-PR, Brazil, between 2015 and 2016. A test to identify the alcohol consumption level was used at the beginning/end of the actions. Cohen's effect size and paired t-test were used to identify the impact of the actions on the reduction of alcohol intake. Results: Six participants ceased alcohol consumption, four showed high level of consumption and one presented average consumption. The paired t-test result suggested statistically significant difference between the initial and final scores, as well as 0.76 effect size. Conclusion: The brief intervention associated with the art therapy resulted in significant impact in reducing alcohol consumption. Investing in the continuous training of primary health care professionals is crucial to consolidate the improvements achieved.

RESUMEN Objetivo: Evaluar el impacto de la intervención breve junto con la arteterapia en usuarios que consumen alcohol. Método: Diseño intragrupo, siendo realizado entre 2015 y 2016, con la participación de 11 alcohólicos de la ciudad de Tamarana (PR, Brasil). Se realizó una prueba para identificar el nivel de consumo de alcohol antes y después de las acciones, y se calcularon el tamaño del efecto de Cohen y la prueba t pareada para evaluar el impacto de las acciones en la reducción del consumo de alcohol. Resultados: Seis dejaron de consumir alcohol, cuatro presentaron un alto consumo y uno presentó un consumo mediano. El resultado de la prueba t pareada reveló una diferencia estadísticamente significativa entre los puntajes inicial y final, así como en el tamaño del efecto con un 0,76. Conclusión: La intervención breve asociada a la arteterapia tuvo un gran impacto en la disminuición del consumo de alcohol. Es fundamental invertir en la educación continuada de los profesionales de la atención primaria de salud para consolidar las mejoras obtenidas.

RESUMO Objetivo: Identificar o impacto da intervenção breve em conjunto com a arteterapia em usuários que consomem álcool. Método: Delineamento intragrupo, com 11 alcoolistas na cidade de Tamarana-PR, entre 2015 e 2016. Foi utilizado um teste para identificação do nível de consumo de álcool ao início/término das ações e calculada a medida de efeito de Cohen e teste t pareado, para identificar o impacto das ações na redução do consumo de álcool. Resultados: Houve seis cessares do consumo de álcool, quatro apresentaram nível elevado de consumo e um apresentou consumo mediano. O resultado do teste t pareado sugeriu diferença estatisticamente significativa entre os escores iniciais e finais, assim como a medida de efeito de 0,76. Conclusão: A intervenção breve associada à arteterapia resultaram em grande impacto para a redução do consumo de álcool. É fundamental investir na educação continuada dos profissionais da atenção primária em saúde para consolidar as melhorias obtidas.

Terapias complementares no trabalho de parto: ensaio clínico randomizado / Terapias complementarias en el trabajo de parto: ensayo clínico randomizado / Complementary therapies in labor: randomized clinical trial

Resumo OBJETIVO: Avaliar o efeito do banho quente de chuveiro e exercício perineal com bola suíça isolados e de forma combinada, sobre a percepção da dor, ansiedade e progressão do trabalho de parto. MÉTODO: Ensaio clínico randomizado e controlado com 128 parturientes alocadas em três grupos de terapias, banho, bola, isolados e combinados. A percepção da dor e ansiedade foi avaliada antes e trinta minutos após a intervenção terapêutica por meio de escala visual analógica (EVA). RESULTADOS: Houve aumento no escore de dor e redução da ansiedade em todos os grupos, sobretudo quando utilizaram banho de chuveiro. A dilatação cervical, aumentou em todos os grupos de intervenção (p<,001) bem como o número de contrações uterinas, principalmente quem utilizou banho e bola associados como também mostrou menor duração do tempo de trabalho de parto. CONCLUSÃO: As terapias estudadas contribuem para adaptação e bem-estar materno e favorecem a evolução do trabalho de parto.

Resumen OBJETIVO: Evaluar el efecto de la ducha caliente y del ejercicio perineal con pelota suiza, separadamente y de forma combinada, sobre la percepción del dolor, la ansiedad y la progresión del trabajo de parto. MÉTODO: Ensayo clínico aleatorizado y controlado junto a 128 parturientes asignadas en tres grupos de terapias, ducha caliente, pelota suiza separadamente y de forma combinada. La percepción de dolor y de ansiedad se evaluó antes y treinta minutos después de la intervención terapéutica por medio de escala visual analógica. RESULTADOS: Hubo un incremento en la puntuación de dolor y una reducción de la ansiedad en todos los grupos, sobre todo cuando se utilizó la ducha. La dilatación cervical aumentó en todos los grupos de intervención (p<,001) así como el número de contracciones uterinas, principalmente en el grupo que utilizó las dos terapias combinadas, ducha caliente con pelota suiza. Asimismo se constató menor duración del tiempo de trabajo de parto. CONCLUSIÓN: Las terapias estudiadas contribuyen a la adaptación y el bienestar materno y favorecen la evolución del trabajo de parto.

Abstract OBJECTIVE: To evaluate the effect of isolated and combined warm shower bath and perineal exercise with Swiss ball, on perception of pain, anxiety and labor progression. METHOD: Randomized, controlled clinical trial with 128 patients allocated into three groups of therapies: isolated and combined bath and ball. Pain and anxiety perception was evaluated before and thirty minutes after therapeutic intervention through visual analogic scales (VAS). RESULTS: Pain perception score increased, and anxiety decreased in all groups, mainly when using a shower bath. The cervical dilation increased in all groups (p<.001), as well as the number of uterine contractions increased, mainly in the group that used combined bath and ball and also showed shorter labor time. CONCLUSION: The studied therapies contribute to maternal adaptation and well-being and favor labor's evolution.

Treatment of post-intubation laryngeal granulomas: systematic review and proportional meta-analysis / Treatment of post-intubation laryngeal granulomas: systematic review and proportional meta-analysis

Abstract Introduction: Laryngeal granulomas post intubation are benign but recurrent lesions. There is no consensus for its treatment. Objective: To describe the effectiveness of different treatment modalities for primary or recurrent laryngeal granulomas resulting from endotracheal intubation. Methods: Systematic review and proportional meta-analysis. Eligibility criteria - experimental or observational studies with at least five subjects. Outcomes studied - granuloma resolution, recurrence, and time for resolution. Databases used - Pubmed, Embase, Lilacs, and Cochrane. The Stats Direct 3.0.121 program was used. Results: Six studies were selected, with 85 patients. The treatments registered were: antireflux therapy, speech therapy, anti-inflammatory drugs, steroids, antibiotics, zinc sulfate and surgery. 85 patients from six studies had primary treatment: surgery ± associations (41 patients), resolution chance 75% (95% CI: 0.3-100%, I 2 = 90%), absolute relapse risk 25% (95% CI: 0.2-71%); medical treatment (44 patients), resolution chance 86% (95% CI: 67-97%); and absolute relapse risk 14% (95% CI: 3-33%). There was no significant difference between groups. Three studies, encompassing 19 patients, analyzed secondary treatment (failure or recurrence after primary treatment); three subjects presented new recurrence. The time needed to resolve the lesions varied from immediate, after surgery, to 23 months, for inhaled steroid. Conclusion: There is no evidence of high quality that proves the efficacy of any treatment for laryngeal granulomas resulting from endotracheal intubation.

Resumo: Introdução: Granulomas laríngeos pós-intubação são lesões laríngeas benignas, porém recorrentes. Não há um consenso na literatura em relação ao seu tratamento. Objetivo: Descrever a eficácia de diferentes modalidades de tratamento para granulomas laríngeos primários ou recorrentes resultantes da intubação endotraqueal. Método: Estudo-revisão sistemática e metanálise proporcional. Critérios de elegibilidade: estudos experimentais ou observacionais com pelo menos cinco indivíduos. Desfechos estudados: resolução do granuloma, recorrência e tempo de resolução. Bases de dados usadas: Pubmed, Embase, Lilacs e Cochrane. Foi usado o software Stats Direct 3.0.121. Resultados: Foram selecionados seis estudos, com 85 pacientes. Os tratamentos registrados foram: terapia antirrefluxo, terapia da voz, medicamentos anti-inflamatórios, esteroides, antibióticos, sulfato de zinco e cirurgia. Receberam tratamento primário 85 pacientes de seis estudos: cirurgia ± associações (41 pacientes), chance de resolução de 75% (IC 95% 0,3% a 100%, I2 = 90%) e risco absoluto de recorrência de 25% (IC 95%: 0,2% a 71%); tratamento clínico (44 pacientes), chance de resolução de 86% (IC 95%: 67% a 97%) e risco absoluto de recorrência de 14% (IC 95%: 3% a 33%). Não houve diferença significante entre os grupos. Três estudos, que abrangeram 19 pacientes, analisaram o tratamento secundário (falha ou recorrência após o tratamento primário); três indivíduos apresentaram nova recorrência. O tempo necessário para resolver as lesões variou de imediato, logo após a cirurgia, até 23 meses, com tratamento com esteroides inalados. Conclusão: Não há evidências de alta qualidade que provem a eficácia de qualquer tratamento para granulomas laríngeos resultantes da intubação endotraqueal.

Percutaneous endoscopic debridement and irrigation for thoracic infections

SUMMARY OBJECTIVE: To investigate the safety and efficacy of percutaneous endoscopic debridement and irrigation for thoracic infections and to make an appropriate choice according to the patient's condition. METHODS. Thirty patients with thoracic infections who received surgical treatment from August 2014 to December2016 were retrospectively analyzed. There were 16 males and 14 females, aged from 41 to 90 years, with an average of 64.4 years. A total of 9 cases were treated with percutaneous endoscopic debridement and irrigation (minimal group), and 21 cases were treated with open debridement in combination with pedicle screw fixation (conventional group). Patients underwent follow-up for 1 month. General condition, operative index, laboratory results, and imaging features were recorded. RESULTS. Compared with the conventional group, there were more comorbidities in patients in the minimal group (8 cases in the minimal group, 10 cases in the conventional group, P=0.049), shorter hospital stay (10.1 + 2.26 days in the minimal group, 16.1 + 6.81 days in the conventional group, P=0.016), less bleeding volume (383.3 + 229.86ml in the minimal group, 90 + 11.18ml in the conventional group, P=0.000), lower VAS score at discharge (2.9 + 0.93 in the minimal group, 3.9 + 0.91 in the conventional group, P=0.013). There was no spinal instability case in the minimal group, 10 cases in the conventional group, P=0.013. There were significant differences. The C reaction protein prior to operation in the minimal group was 28.4±7.50mg/L. Compared with 45.1 + 15.78mg/L in the conventional group, P=0.005, it was lower. CONCLUSIONS. Percutaneous endoscopic debridement and irrigation are an effective surgery for treatment of thoracic infections, especially suitable for patients with comorbidities and poor general condition. However, for severe infection and spinal instability, we tend to choose open surgery in combination with fixation.

RESUMO OBJETIVOS: Investigar a eficácia e segurança de desbridamento endoscópico percutâneo e irrigação torácica para infecções e fazer uma escolha adequada de acordo com a condição do paciente. MÉTODOS: Trinta pacientes com infecção torácica que receberam tratamento cirúrgico de agosto de 2014 a dezembro de 2016 foram analisadosretrospectivamente. Havia 16 homens e 14 mulheres, de 41 a 90 anos, com uma média de 64,4 anos. Nove casos foram tratados com desbridamento endoscópico percutâneo e irrigação (grupo mínimo) e 21 casos foram tratados com desbridamento aberto em combinação com fixação do parafuso pedicular(grupo convencional). Os pacientes foram submetidos a acompanhamento durante um mês. Estado geral, índice operacional, resultados de laboratório e imagem e funcionalidades foram gravados. RESULTADOS: Em comparação com o grupo convencional, há mais comorbidades em pacientes do grupo mínimo (8 casos no grupo mínimo, 10 casos no grupo convencional, P = 0,049), menos tempo no hospital (10,1 + 2,26 dias no grupo mínimo, 16,1 + 6,81 dias no grupo convencional, P = 0,016), menos volume de sangramento (383,3 + 229,86 ml no grupo mínimo, 90 + 11,18 ml no grupo convencional, P = 0,000), menor pontuação no VAS a quitação (2,9 + 0,93 no grupo mínimo, 3,9 + 0,91 no grupo convencional, P = 0,013). Não houve nenhum caso de instabilidade espinhal no grupo mínimo, e 10 casos no grupo convencional, P = 0,013. Houve diferenças significativas. O nível de proteína C-reativa antes da operação no grupo mínimo era de 28,4±7,50mg/L. Em comparação com 45,1 + 15,78 mg/L no grupo convencional, P = 0,005, era mais baixa. CONCLUSÃO: O método de desbridamento endoscópico percutâneo e irrigação é eficaz para o tratamento de infecções em cirurgia torácica, especialmente adequado para pacientes com comorbidades e mau estado geral. Mas, para a infecção grave e instabilidade vertebral, tendemos a escolher a cirurgia aberta em combinação com a fixação.

Tazarotene gel with narrow-band UVB phototherapy: a synergistic combination in psoriasis

Abstract: BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance. RESULT: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy. STUDY LIMITATIONS: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period. CONCLUSION: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.

Terapia de reemplazo renal continua en el paciente con oxigenación por membrana extracorpórea: consideraciones para la combinación de ambas terapias / Continuous renal replacement therapy in patients with extracorporeal membrane oxygenation

The presence of renal dysfunction is not unusual in patients with pulmonary or cardiac dysfunction who require rescue with extracorporeal membrane oxygenation (ECMO). The complexity, implicit in the implementation of both techniques, can be overwhelming. This review aims to explain the most important aspects of continuous renal replacement therapy in a patient with extracorporeal support.

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.

Manejo de la infección por Helicobacter pylori: apreciación crítica de la literatura / Treatment of the Helicobacter pylori Infection: A Critical Appraisal of the Literature

Introducción: la infección por Helicobacter pylori es un problema de salud pública, dada su relación con cáncer gástrico. El incremento de la resistencia bacteriana limita la erradicación efectiva, a pesar del empleo de diferentes esquemas de tratamiento. Métodos: revisión de la literatura en la base de datos Pubmed/Medline entre el 1 de enero de 2015 y el 31 de diciembre de 2016 sobre el manejo del Helicobacter pylori. Resultados: se incluyeron 26 artículos. La terapia secuencial sobresale como opción de tratamiento de primera línea para escenarios como Colombia. La implementación de coadyuvantes puede influir en las tasas de erradicación. Los estudios de epidemiología local y costo-efectividad son escasos. Conclusiones: el uso y conocimiento adecuado de los esquemas de manejo puede disminuir los costos para el sistema, la resistencia antimicrobiana y favorecer la erradicación de patógenos. Se requieren estudios para generar recomendaciones locales.

Introduction: Helicobacter pylori (H. pylori) infection is a public health problem due to its relationship with gastric cáncer The escalation of antibiotic resistance hampers an effective eradication, despite the availability of treatment options. Methods: A review of the literature was performed in the database PubMed between 01/01/2015 and 31/31/2016. Results: Twenty six articles were included. Sequential therapy stands out as a first line therapy for scenarios such as Colombia. The implementation of adjuvants may have a positive impact on eradication rates. Local epidemiólogo- and cost-effectiveness studies are scarce. The results were analized by erradication therapies, coadyuvant treatment, guidelines and outcomes non mentioned in the guidelines. Conclusions: The correct use and knowledge of the different treatment options could reduce the costs for the health systems, the antibiotics resistance and could favor pathogen eradication. Further studies are required for establishing local recommendations.

Avaliação do potencial de superação da quimioresistência do melanoma aos inibidores de BRAFV600E (Vemurafenibe) e de MEK (Trametinibe) utilizando terapia combinatória com 4-nerolidilcatecol (4-NC) / Evaluation of the potential of overcoming the chemoresistance of melanoma to BRAFV600E (Vemurafenib) and MEK (Trametinib) inhibitors using combinatory therapy with 4-nerolidylcatechol (4-NC)

Embora o melanoma represente apenas 4% das neoplasias malignas da pele, é considerado a mais grave por ser altamente etal. Em virtude da via MAPK (Mitogen activated protein kinase) estar intimamente ligada ao descontrole da proliferação celular, especialmente em melanoma, esta via se tornou um alvo para o desenvolvimento de terapias direcionadas a oncogenes, como os potentes quimioterápicos Vemurafenibe (inibidor da mutação V600E em BRAF - BRAFV600E) e Trametinibe (inibidor de MEK). Cada vez mais, melhores taxas de respostas vêm sendo alcançadas com os novos medicamentos, porém a maioria dos pacientes está sujeita a recidivas após 7 meses de tratamento devido ao desenvolvimento de quimioresistência, justificando a constante busca por novos compostos terapêuticos. Dados de nosso laboratório indicam que 4-nerolidilcatecol (4-NC) induz aumento na expressão de p53, produção de ROS e dano ao DNA, culminando em apoptose dependente de caspase-3 em células de melanoma por ser um inibidor proteassomal. Além disto, o 4-nerolidilcatecol (4- NC) demonstrou efeito inibitório na proliferação de células de melanoma em modelo de cultura organotípica de pele. Desta forma, este projeto visa avaliar a possibilidade de superação da quimioresistência aos inibidores de BRAF e de MEK, utilizando terapias combinatórias com 4-NC em células de melanoma humano resistentes a estes inibidores. Primeiramente, linhagens celulares de melanoma resistentes aos inibidores de BRAF (R) e BRAF/MEK (DR) foram geradas a partir de células parentais BRAF mutadas (P) e caracterizadas por MTT, microscopia de fluorescência e western blotting. Estas células foram submetidas ao tratamento com 4-NC que apresentou citotoxicidade na concentração de 30µM, inibição de formação de colônias e diminuição na invasão em modelos in vitro de culturas 2D e 3D em todas as linhagens estudadas (P, R e DR). O 4-NC foi ainda capaz de induzir estresse de retículo endoplasmático com indução de apoptose. Visando a explorar o efeito terapêutico in vivo do 4-NC, outro estudo foi conduzido em animais submetidos a enxerto xenográfico com células parentais de melanoma NRAS mutadas. Após desenvolvimento do tumor, os animais foram tratados 3 vezes por semana durante 3 semanas com 4-NC (10 mg/kg) por via i.p. O 4-NC foi capaz de inibir em até 4 vezes o crescimento dos tumores xenográficos (4/10) quando comparado com os controles, com remissão completa do tumor em um animal. A expressão de p53 e PARP clivada foi aumentada nos tumores dos animais tratados, sugerindo apoptose. A expressão gênica de MMP2 e MMP14 estava diminuída nas mesmas amostras, demonstrando o papel do 4-NC na inibição da invasão do melanoma in vivo. Finalmente, a toxicidade sistêmica do 4-NC foi avaliada nas mesmas doses empregadas no ensaio in vivo de tumorigênese. A baixa toxicidade observada nos ensaios toxicológicos com tratamentos sub-crônicos com 4-NC e a citotoxicidade demonstrada em modelos xenográficos nos leva a considerar este composto como promissor para estudos futuros e sua aplicação no tratamento do melanoma cutâneo humano, incluindo pacientes resistentes aos inibidores de BRAF e MEK

Melanoma accounts for only 4% of malignant neoplasms of the skin, but is considered the most serious because it is highly deadly. Because the MAPK (Mitogen activated protein kinase) pathway is closely linked to the lack of control of cell proliferation, especially in melanoma, this pathway has become a target for the development of oncogene-targeted therapies, such as the potent chemotherapeutic agents Vemurafenib (V600E mutation inhibitor in BRAF - BRAFV600E) and Trametinib (MEK inhibitor). Increasingly, better response rates have been achieved with the new drugs, but most patients are subject to relapses after 7 months of treatment due to several mechanisms, which justify the constant search for new therapeutic compounds. Data from our laboratory indicate that 4-nerolidylcatechol (4-NC) induces increased p53 expression, ROS production and DNA damage, culminating in caspase-3 dependent apoptosis in melanoma cells. The 4-NC compound demonstrated an inhibitory effect on melanoma cell proliferation in an organotypic skin culture model. Thus, this project aims to evaluate the possibility of overcoming the existing chemoresistance to BRAF and MEK inhibitors, using 4-NC combinatory therapies in human melanoma cells resistant to these inhibitors. Firstly, melanoma cell lines resistant to BRAF (R) and BRAF / MEK (DR) inhibitors were generated from naive cells mutated BRAF (N) and characterized by MTT, fluorescence microscopy and western blotting. These cells were submitted to 4-NC treatment that showed cytotoxicity with 30 µM, inhibition of colony formation and decrease in invasion in 2D and 3D in vitro models in all cell line studied (N, R and DR). Furthermore, 4-NC was able to induce endoplasmic reticulum stress with apoptosis induction. In order to explore the in vivo therapeutic effect of 4-NC, an additional study was conducted using xenograft model with NRAS-mutated melanoma cell line. After tumor development, the animals were treated 3 times per week for 3 weeks with 4-NC (10 mg / kg) by i.p. injection. 4-NC was able to inhibit up to 4- fold the growth of xenograft tumors (4/10) when compared to controls, with complete tumor remission in one animal. Cleaved PARP and p53 expression were increased in the tumors of treated animals, suggesting apoptosis. MMP2 and MMP14 gene expression were decreased in the same samples, demonstrating the role of 4-NC in inhibiting melanoma invasion in vivo. Finally, the systemic toxicity of 4-NC was evaluated at the same doses employed in the in vivo tumorigenesis assay. The low toxicity observed in the toxicological assays with sub-chronic 4- NC treatments and the demonstrated cytotoxicity in xenograft models leads us to consider this compound as promising for future studies and its application in the treatment of cutaneous human melanoma, including patients resistants to BRAF and MEK inhibitors

Comparative effectiveness of photobiomodulation and manual therapy alone or combined in TMD patients: a randomized clinical trial

Abstract The effectiveness of photobiomodulation (PBM) and manual therapy (MT), alone or combined (CT), were evaluated in pain intensity, mandibular movements, psychosocial aspects, and anxiety symptoms of temporomandibular disorder (TMD) patients. Fifty-one TMD patients were randomly assigned to three groups: the PBM group (n = 18), which received PBM with 808 nm, 100 mW, 13.3 J/cm2, and 4 J per point; the MT group (n=16) for 21 minutes each session on masticatory muscles and temporomandibular joint TMJ; and the CT group (n = 17), applied during twelve sessions. Seven evaluations were performed in different moments using visual analogue scale (VAS), Research Diagnosis Criteria for Temporomandibular Disorders (RDC/TMD) Axis I and II, and Beck anxiety inventory (BAI). All groups demonstrated reductions in pain and improvement in jaw movements during treatment and at follow-up (< 0.001). The assessment of psychosocial aspects of TMD, comparing baseline and follow-up in all treatment groups, revealed that treatment did not promote modification in the intensity of chronic pain (p > 0.05). However, depression symptoms showed a reduction in PBM and CT groups (p≤0.05). All treatments promoted reduction in physical symptoms with and without pain and enhancement of jaw disabilities (p ≤ 0.05). MT promotes improvement in 5 functions, PBM in 2, and CT in 1 (p < 0.001). BAI analysis revealed that all treatments lead to a reduction in anxiety symptoms (p≤0.05). All protocols tested were able to promote pain relief, improve mandibular function, and reduce the negative psychosocial aspects and levels of anxiety in TMD patients. However, the combination of PBM and MT did not promote an increase in the effectiveness of both therapies alone.

Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases / Tratamento bem-sucedido de leucemia mieloide aguda recorrente após transplante com duplicação interna em tandem FLT3 usando combinação de indução por quimioterapia, infusão de linfócitos de doador, soferanib e azacitidina. Relato de três casos

ABSTRACT Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.

RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.

Immunotherapy and gene therapy as novel treatments for cancer / Inmunoterapia y terapia génica como nuevos tratamientos contra el cáncer

Abstract The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is an anti-CTLA-4 antibody which demonstrated good results when administered to patients with melanoma. Gene therapy has also shown promising results in clinical trials. Particularly, Herpes simplex virus (HSV)-mediated delivery of the HSV thymidine kinase (TK) gene to tumor cells in combination with ganciclovir (GCV) may provide an effective suicide gene therapy for destruction of glioblastomas, prostate tumors and other neoplasias by recruiting tumor-infiltrating lymphocytes into the tumor. The development of new treatment strategies or combination of available innovative therapies to improve cell cytotoxic T lymphocytes trafficking into the tumor mass and the production of inhibitory molecules blocking tumor tissue immune-tolerance are crucial to improve the efficacy of cancer therapy.

Resumen El sistema inmune interactúa íntimamente con los tumores durante el proceso del desarrollo de la enfermedad y su progresión a metástasis. Esta compleja comunicación entre el sistema inmune y las células tumorales puede prevenir o promover el crecimiento del tumor. Los nuevos enfoques terapéuticos que aprovechan los mecanismos inmunológicos, ya sea por el bloqueo de señales inhibitorias o por la activación directa de células efectoras, han mostrado resultados prometedores. El bloqueo de puntos de control inmunológicos (immune-checkpoints) con anticuerpos monoclonales dirigidos contra receptores que normalmente inhiben el sistema inmune, como CTLA-4 o PD-1, ha resultado ser un tratamiento exitoso para pacientes con melanoma avanzado. El fármaco ipilimumab es un anticuerpo anti-CTLA-4 que ha demostrado buenos resultados terapéuticos en pacientes con melanoma. Por otro lado, la terapia génica también ha mostrado resultados prometedores en ensayos clínicos. En especial, la administración de la enzima timidina quinasa del virus Herpes simplex (HSV-TK) en combinación con el fármaco ganciclovir (GCV) ha mostrado ser una terapia suicida muy efectiva para la destrucción de diferentes neoplasias incluyendo glioblastomas y tumores prostáticos, por un mecanismo que involucra el reclutamiento de linfocitos infiltrantes de tumor. Es importante la búsqueda de nuevas estrategias o la combinación de terapias innovadoras, con el fin de involucrar tanto la atracción de linfocitos citotóxicos así como el empleo de moléculas que inhiban la inmunotolerancia del tejido tumoral para mejorar la eficiencia de los tratamientos contra el cáncer.

Alternative ways to optimize treatment for retinal vein occlusion with peripheral capillary non-perfusion: a pilot study / Opções alternativas para otimizar o tratamento da oclusão da veia retiniana sem perfusão capilar periférica (um estudo piloto)

ABSTRACT Purpose: We compared the efficacy and safety of ranibizumab versus ranibizumab plus scatter laser photocoagulation (SLP) in patients with chronic post-central retinal vein occlusion (CRVO) macular edema (ME). Methods: This prospective non-randomized pilot study included 250 patients with peripheral retinal ischemia and CRVO-related ME. The mean follow-up period was 24.5 ± 6.5 months. The clinical assessments conducted included best corrected visual acuity, optical coherence tomography, and multi-field fluorescein angiography with measurement of the ischemic area. The study population comprised two comparable patient groups with peripheral retinal ischemia that received different treatments for post-CRVO ME: ranibizumab with peripheral SLP of capillary non-perfusion areas (Group 1); and Lucentis® monotherapy (Group 2). Data analyses were performed using Statistica 7 software suite and included the estimation of х ± δ values and their dispersion and covariation coefficients at different stages of the study. Results: Clinically significant retinal ischemia was detected in 175 (70%) patients, occupying an average of 435.12 ± 225.13 mm2, i.e., 167.15 ± 45.16 optic disc areas. Peripheral ischemia was found in 125 patients, representing 50% of all patients with CRVO and 71.4% of all patients with ischemic CRVO. The mean number of ranibizumab injections in patients who underwent SLP was 3.5 ± 1.6. Patients treated with ranibizumab monotherapy for 24 months received 10.6 ± 2.5 injections. Functional and anatomic results were comparable in the two groups. Conclusions: The combination of ranibizumab injections and peripheral SLP in capillary non-perfusion areas can significantly decrease the number of injections and reduce neovascular complications.

RESUMO Objetivo: A investigação centra-se na terapia de edema macular pós-oclusão da veia retiniana central (OVCR) em casos com isquemia retiniana periférica. O objetivo foi comparar a eficácia e a segurança do tratamento com ranibizumab vs ranibizumab + fotocoagulação com laser de dispersão (SLP) em pacientes com edema macular crônico secundário a oclusão da veia retiniana central isquêmica. Métodos: O estudo prospectivo não-randomizado incluiu 250 pacientes com isquemia retiniana periférica e edema macular relacionados a oclusão da veia retiniana central. O tempo médio de seguimento foi de 24,5 ± 6,5 meses. A avaliação clínica incluiu acuidade visual melhor corrigida, tomografia de coerência óptica (OCT) e angiografia por fluoresceína multi-campo com a medição da área de isquemia. A população estudada foi constituída por dois grupos de pacientes comparáveis com o oclusão da veia retiniana central isquêmica, que receberam tratamento diferente. Em nossa prática anterior, utilizamos ranibizumab (Lucentis®) em monoterapia (de acordo com a licença do medicamento) para edema macular pós-oclusão da veia retiniana central com isquemia retiniana periférica (Grupo 2). Mais recentemente, começamos a combinar ranibizumab com SLP periférica de áreas não perfusão capilar (Grupo 1). As análises de dados foram realizadas com o software Statistica 7 e incluíram a estimação dos valores de х ± δ e seus coeficientes de dispersão e covariân cia em diferentes estágios do estudo. Resultados: Identificou-se isquemia retiniana clinicamente significativa em 175 (70%) pacientes, atingindo uma média de 435,12 ± 225,13 mm2, ou seja, 167,15 ± 45,16 áreas de disco óptico. Isquemia periférica foi encontrada em 125 casos, representando 50% de todos os pacientes com oclusão da veia retiniana central e 71,4% de todos os pacientes com oclusão da veia retiniana central isquêmica. O número médio de injeções de rani bizumab em pacientes com SLP foi de 3,5 ± 1,6. Os pacientes tratados com ranibizu mab em monoterapia durante 24 meses receberam 10,6 ± 2,5 injeções. Os resultados funcionais e anatômicos foram comparáveis nos dois grupos. Conclusões: A combinação de injeções de ranibizumab com SLP periférica em áreas de não-perfusão capilar pode diminuir significativamente o número de injeções e reduzir as complicações neovasculares.