A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.

PURPOSE: EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. EXPERIMENTAL DESIGN: To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. RESULTS: Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. CONCLUSIONS: Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR.

Superior Efficacy and Safety of a Nonemulsive Variant of the NGcGM3/VSSP Vaccine in Advanced Breast Cancer Patients.

NGcGM3 ganglioside is a tumor-specific antigen expressed in human breast tumors. The NGcGM3/VSSP vaccine, consisting in very small-sized proteoliposomes (VSSP) obtained by the incorporation of NGcGM3 into the outer membrane protein complex of Neisseria meningitidis, has been previously tested in a Phase II trial in patients with metastatic breast cancer (MBC) but emulsified with Montanide ISA 51. An Expanded Access study was carried out in MBC patients aiming to find if a nonemulsive formulation of NGcGM3/VSSP, without Montanide ISA 51, could be more safe and effective. A total of 104 patients were vaccinated with the nonemulsive formulation (900 µg), subcutaneously (SC), or with the emulsive formulation (200 µg), intramuscularly (IM). An intent-to-treat analysis of efficacy was performed with all patients, and 93 patients were split off according to the site of metastases (visceral/nonvisceral). Of note, SC-treated patients exhibited a superior median overall survival (OS) than IM-treated patients (23.6 vs. 8.2 months; log rank P = 0.001). Even though in the subset of patients with nonvisceral metastases SC vaccination duplicated the median OS compared to the alternative option (31.6 vs. 16.5 months), this difference did not reach statistical significance (log rank P = 0.118). Curiously, in patients with visceral metastases, the advantage of the nonemulsive formulation was more apparent (median OS 21.0 vs. 6.2 months; log rank P = 0.005). The vaccine was safe for both formulations.

A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients.

PURPOSE: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS). RESULTS: One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46-0.87; P = 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53-0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times. CONCLUSIONS: Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC.

Efectividad del masaje tuina como tratamiento para el alivio de dolor a pacientes sometidos a hemodiálisis / Effectiveness of the Tuine massage like a treatment for the relieve of pain in patients with hemodyalisis

Se realizó un estudio de intervención terapéutica con el objetivo de evaluar la efectividad del masaje tuiná en el tratamiento del dolor en los miembros inferiores en pacientes con insuficiencia renal crónica sometidos a hemodiálisis en el servicio de nefrología del Hospital Clínico Quirúrgico Universitario Celia Sánchez Manduley de Manzanillo en el periodo comprendido entre junio del 2011 a mayo del 2012. El estudio se llevó a cabo con los 125 pacientes con insuficiencia renal crónica atendidos en la institución los cuales se dividieron en forma aleatoria en 63 y 62 para grupo control y grupo de experimentación respectivamente. La fuente primaria de información fueron los pacientes en estudio y como fuentes secundarias, las historias clínicas de los mismos, de donde se obtuvieron variables como: la edad, sexo, tiempo de aparición del dolor, tiempo de persistencia del dolor y satisfacción del paciente; se utilizaron medidas estadísticas como números absolutos, porcientos, distribución de frecuencia y prueba de hipótesis para la proporción. Se pudo apreciar que el masaje tuiná es efectivo para el tratamiento del dolor de miembros inferiores en pacientes sometidos a hemodiálisis dado que la persistencia del dolor no rebasa la media hora después de presentarse, en la mayoría de los casos, a pesar de ser de tipo moderado a ligero según la escala visual análoga empleada(AU)

It was performed a study of therapeutic intervention with the aim to evaluate the effectiveness of the Tuiná massage in the treatment of the pain in lower members in patients with Chronic Renal Insufficiency, subjected to hemodyalisis in the nephrology service at Celia Sánchez Manduley surgical clinical university hospital in Manzanillo in the period between June of the 2011 to May of the 2012. The study was carried out with the 125 patients with chronic renal insufficiency assisted in the institutions which were randomly divided into 63 and 62 for the experimental and control group. The primary source of information were the patients under study and like the secondary source, their clinical antecedents, from which there were obtained variables like: the age, sex, time of appearance of the pain, time of persistence of the pain and satisfaction of the patient; there were used statistical measures like the absolute numbers, percents, distribution of frequency and hypothesis test for the proportion. I could be appreciated that the Tuiná massage was effective for the treatment of the pain of the lower members in patients subjected to hemodyalisis, because the persistence of the pain did not pass the half hour, in the majority of the cases, in spite of being from moderated to slight, according to the analogous visual scale applied(EU)

Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer.

The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

Factores de riesgo de la infeccion neonatal / Risk factors of neonatal infection

La infección neonatal representa un desafío creciente en las Unidades de Neonatología. Por este motivo se realizó un estudio analítico de tipo caso control no pareado en el Hospital Materno Norte Tamara Bunke de Santiago de Cuba, con el objetivo de identificar los principales factores de riesgo que influyeron en la aparición y desarrollo de las infecciones neonatales y determinar el impacto que se produciría sobre la mortalidad si se lograra controlarlos. El universo estuvo representado por 66 casos recién nacidos diagnosticados con infección neonatal y 132 controles (neonatos que no presentaban este diagnóstico). En el análisis se utilizó el porcentaje y la razón, como medidas de resumen para variables cualitativas, se midió la fuerza de asociación mediante la razón de productos cruzados OR, con nivel de significación del 5 por ciento, para determinar el impacto que se produciría si lográramos controlar estos factores se calculó el riesgo atribuible porcentual en expuestos. Resultando la canalización umbilical con OR= 24,02, la infección vaginal OR= 9,35, el tiempo de trabajo de parto prolongado OR= 6,50, y el politacto OR= 5,97 los factores de riesgo asociados a la infección en el neonato. Si se controlaran, se lograría un mayor impacto en la reducción de la incidencia de esta infección. Se recomienda implementar estrategias en los diferentes niveles de atención de salud para modificar conocimientos en este tema(AU)

The neonatal infection represents an increasing challenge in the Neonatology Units. Due to this reason it was performed a non-matched case-control-analytic research at Tamara Bunke Maternal Hospital from Santiago de Cuba, with the objective to identify the main risk factors that influenced in the presence and development of neonatal infections and to determine the impact that would be produced upon the mortality if they could be controlled. The universe was represented by 66 newborn cases diagnosed with neonatal infection and 132 controls (neonates without this diagnosis). In the analysis the percentage and the reason were used as measures of qualitative variables, it was measured the association strength through OR cross products with significant levels of 5 percent to determine the impact that would be produced if we could control these factors. It was calculated the percentage risk in exposures resulting the umbilical canalization with OR= 24,02, the vaginal infection OR= 9,35, the time of prolongued labour OR= 6,50 and the polytract OR= 5,97, the risk factors associated to the neonate infection. Controlling all these factors would be important to obtain a greater impact in the reduction of the incidence of this infection. It is recommended the implementation of strategies in the different levels of health assistance in order to modify the kowledge about this topic(EU)

Estrategia metodológica para favorecer el desarrollo de habilidades en la asignatura informática medica I / Methodological strategy to favour the skill development of the Medical Informatic I

La realización de esta investigación se basa en los resultados obtenidos en la asignatura Informática Médica I, los que demuestran insuficientes habilidades informáticas en los estudiantes de primer año de la carrera de Medicina; además los controles a clase han evidenciado que al profesor se le hace difícil tratar toda materia en el tiempo disponible. La independencia de los alumnos es limitada ya que no poseen la bibliografía actualizada. Esta investigación consiste en diseñar un curso interactivo por Internet, utilizando la plataforma MOODLE, mediante el cual los estudiantes podrán adquirir conocimientos relacionados con el Sistema Operativo (crear, copiar, cortar, cambiar nombre, eliminar y buscar archivos y carpetas); los servicios más usados de Internet (buscar información y utilización del correo); algunas aplicaciones del Office (Word, Power Point y Access); así como la estrategia metodológica que permita favorecer el desarrollo de habilidades informáticas a través de las tecnologías de las Informáticas y las Comunicaciones. El diseño del curso contempla el acceso de los estudiantes de forma interactiva a los textos básicos, a un conjunto de artículos científicos relacionados con los temas de objeto de estudio, la interacción constante con el profesor y los demás alumnos a través del correo electrónico, chats, foros, listas de discusión y evaluaciones en línea. El empleo de las TIC en nuestra institución es una necesidad del desarrollo alcanzado por la misma, ya que tenemos la posibilidad de acceder a Internet de forma libre para toda la documentación médica(AU)

This research is based on the academic results of the subject Medical Informatics I and it shows that the students from 1rst year do not have the adequate informatic abilities; furthermore, the controls made by the head of the department have shown difficulties for the teachers to teach all the topics in the required period of time. Besides, the degree of independence of the students is limited since they don´t have the updated bibliography. This invetigation focus on designing an interactive course through Internet , and using the MOODLE platform by means of which students will be able to learn about the operative system (create, copy, cutting, change the name, delete and look for file); the mostly used services of Internet (looking for information, e-mail); some applications from office (word, power point and access) as well a the methodological strategy which allows to favour the development of informatic abilities through the technology of informatics and communications. The design of the course involves favours the access of our students, in an interactive way, to the basic text and to a group of scientific issues related to the topics of study, constant interaction with the profesor and the rest of the students by means of e-mails, chats, discussions and evaluations on line. The use of TIC's in our institution is a need for the development that it has reached, since we have access to Internet freely to obtain the medical documentation(EU)

1E10 anti-idiotype vaccine in non-small cell lung cancer: experience in stage IIIb/IV patients.

Conventional treatment of non-small cell lung cancer (NSCLC) has apparently reached a plateau of effectiveness in improving the survival of the patients. For that reason the search for new therapeutic strategies in this type of tumor is justified. 1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to P3 Ab1 MAb, which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some tumors, including those from the lung. We report the treatment with aluminum hydroxide-precipitated 1E10 MAb of 34 stage IIIb and 37 stage IV NSCLC patients. These patients were treated with the anti-idiotype vaccine, after received standard chemotherapy and radiotherapy, in a compassionate-use basis study. Patients received five bi-weekly injections of 1 mg of 1E10/Alum, other 10 doses at 28-day intervals and later the patients who maintained a good performance status continued to be immunized at this same time interval. No evidence of unexpected or serious adverse effects was reported. The median survival time of the 56 patients who entered the study with partial response or disease stabilization and with a PS 1 after the first line of chemo/radiotherapy, was 11.50 months from starting vaccination. In contrast, the median survival time calculated for patients who started vaccination with progressive disease and/or a PS2 was 6.50 months.

Gimnasia pre parto

El montaje computarizado de un tema de la Cultura Física terapéutica y profiláctica está dedicado en especial a la gimnasia pre parto, en el se encuentran recogidas, en 24 presentaciones, los elementos más notorios del tema propuesto, dentro de la misma están plasmadas un programa de ejercicios físicos, ejercicios respiratorios y posturas para descansar todo esto con el objetivo de preparar a la embarazada para un mejor parto. Resulta de fácil manejo por pacientes, especialistas, en Cultura Física, estudiantes y especialista de la Ginecología que con mínimos conocimientos de computación como medio indispensable del saber en el mundo futuro y desarrollo, pueden encontrar la información necesaria y actualizada del tema los estudiantes de 4to y 5to año de medicina quienes reciben estos temas como objeto de estudio en su formación profesional, encontraras en este trabajo un material de apoyo a la docencia(AU)

Un ejemplo de cómo hacer extensión universitaria

El objetivo de este trabajo consistió en lograr una integración de las comunidades intra y extrauniversitarias a través de la creación de un Círculo de interés de informática con los estudiantes del Politécnico de Informática de Manzanillo, con vista a prepararlos para su futuro desempeño profesional. Para alcanzar este objetivo se elaboró un programa para este círculo de interés, actividad sin precedentes en las Universidades de Ciencias Médicas en Cuba. Para la validación de este programa se escogieron al azar diez (10) estudiantes de dicho Politécnico. Se les realizó un diagnóstico inicial donde se pudo comprobar el poco conocimiento básico de esta materia. Hay que tener en cuenta que los encuentros comenzaron a finales de curso. Al cabo de tres meses se logró ampliar los conocimientos de estos estudiantes y lograron realizar una exposición donde realizaron las presentaciones en Power Point(AU)

Comportamiento de un grupo de pacientes diabéticos tratados a través de ejercicios físicos terapéuticos / Behavior of a group of diabetic patients treated with therapeutic exercises

Se aplicó un programa de ejercicio en pacientes que presentan trastornos de salud y entre los cuales la enfermedad primaria era la diabetes mellitus y como asociadas se encontraban la obesidad e hipertensión. En el programa se aplicaron ejercicios de desarrollo físico general los cuales facilitan la preparación y adaptación físico-motora en correspondencia con las exigencias del programa y con los beneficios que se van adquiriendo durante su cumplimiento. Desde el primer encuentro comenzaron a manifestarse cambios sustanciales desde el punto de vista físico espiritual. Es un programa breve, sistemático e individual aunque, se puede trabajar con procedimientos organizativos en grupo garantizando la presencia de los efectos bioquímicos y fisiológicos provocados por la aplicación de ejercicios físicos terapéuticos. Los pacientes que participaron lograron una mejoría en su padecimiento en dependencia de sus intereses motivacionales(AU)

It was applied a program of exercises in patients that presented health disorders such as diabetes mellitus and the associated ones were the obesity and hypertension. In the program there were applied exercises of general physical development which facilitated the preparation and physical –motor adaptation in correspondence with the demands of the program and the profits obtained during its fulfillment. From the first meeting substantial changes were evidenced from the spiritual physical point of view. It is a brief program, systematic and individual although it can be worked with organizational procedures in guaranteed groups for the presence of the biochemical and physiological effects caused by the application of physical therapeutic exercises. The patients that participated got better according to their motivational interests(EU)