Adoptive T cell therapy: Boosting the immune system to fight cancer.

Cellular therapies have shown increasing promise as a cancer treatment. Encouraging results against hematologic malignancies are paving the way to move into solid tumors. In this review, we will focus on T-cell therapies starting from tumor infiltrating lymphocytes (TILs) to optimized T-cell receptor-modified (TCR) cells and chimeric antigen receptor-modified T cells (CAR-Ts). We will discuss the positive preclinical and clinical findings of these approaches, along with some of the persisting barriers that need to be overcome to improve outcomes.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma.

Regional delivery of chimeric antigen receptor (CAR) T cells in glioblastoma represents a rational therapeutic approach as an alternative to intravenous administration to avoid the blood-brain barrier impediment. Here, we developed a fibrin gel that accommodates CAR-T cell loading and promotes their gradual release. Using a model of subtotal glioblastoma resection, we demonstrated that the fibrin-based gel delivery of CAR-T cells within the surgical cavity enables superior antitumor activity compared to CAR-T cells directly inoculated into the tumor resection cavity.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Audiologic and vestibular findings in a sample of human immunodeficiency virus type-1-infected Mexican children under highly active antiretroviral therapy.

OBJECTIVE: There is little information about audiologic and vestibular disorders in pediatric patients infected with the Human Immunodeficiency Virus type-1 (HIV-1). The aim of this study was to evaluate audiologic and vestibular disorders in a sample of HIV-1-infected children receiving Highly Active Antiretroviral Therapy. METHODS: Patients underwent pure tone audiometry, speech discrimination testing, auditory brainstem responses, electronystagmography, and rotatory testing. HIV-1 viral load and absolute CD4+ cell counts were registered. RESULTS: Twenty-three patients were included, aged 4.5 years (median, range 5 months to 16 years). Pure tone audiometry was carried out in 12 children over 4 years of age: 4 (33%) showed hearing loss, 2 were conductive. Auditory brainstem responses were measured in all 23 patients, suggesting conductive hearing loss in 6 and sensorineural hearing loss in 2. Most patients with conductive hearing loss had the antecedent of acute or chronic suppurative otitis media but with dry ears at the time of evaluation (p=0.003). Abnormal prolongations of interwave intervals in auditory brainstem responses were observed in 3 children (13%, 4 ears), an abnormal morphology in different components of auditory brainstem responses in 4 (17.4%, 7 ears), and abnormal amplitude patterns in 11 patients (48%, 17 ears). Vestibular tests were abnormal in all six patients tested, with asymmetries in caloric and rotatory tests. Although differences were not significant, in general, audiologic abnormalities were more frequent in patients with more prolonged HIV-1 infections, higher viral loads, or lower absolute CD4+ cell counts. CONCLUSIONS: Conductive hearing loss associated with previous otitis media events, abnormalities in auditory brainstem responses suggesting disorders at different levels of the auditory pathways, and unilateral vestibular hyporeflexia were frequent findings in our sample of HIV-1-infected children under Highly Active Antiretroviral Therapy. These findings suggest that HIV-1-infected children should be submitted to audiologic and vestibular evaluation as early as possible in order to reduce their impact on the psychosocial development of these patients.

Impact of Standardizing Management of Atrial Fibrillation with Rapid Heart Rate in the Emergency Department.

CONTEXT: There is substantial variation in the emergency treatment of atrial fibrillation with tachycardia. A standardized treatment approach at an academic center decreased admissions without adverse outcomes, but this approach has not been evaluated in a community Emergency Department (ED). OBJECTIVE: To evaluate the implementation of a standardized treatment guideline for patients with atrial fibrillation and a rapid heart rate in a community ED. DESIGN: An observational pre-/postimplementation (August 2013 to July 2014 and August 2014 to July 2015, respectively) study at a community ED. The standardized treatment guideline encouraged early oral treatment with rate control medication, outpatient echocardiogram, and early follow-up. A multiple logistic regression model adjusting for patient characteristics was generated to investigate the association between the intervention and ED discharge rate. MAIN OUTCOME MEASURES: The primary measure was ED discharge. Secondary measures included stroke or death, ED return visit, hospital readmission, length of stay, and use of oral rate control medications. RESULTS: A total of 199 (104 pre/95 post) ED encounters were evaluated. The ED discharge rate increased 14% after intervention (57.7% to 71.6%, p = 0.04), and use of rate control medications increased by 19.4% (p < 0.01). Adjusted multivariate results showed a nearly 2-fold likelihood of ED discharge after guideline implementation (odds ratio = 1.97, 95%confidence interval = 1.07-3.63). Length of stay, return visits, and hospital readmissionswere similar. CONCLUSION: A standardized approach to ED patients with atrial fibrillation and tachycardia is associated with a decrease in hospital admissions without adversely affecting patient safety.

[Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats]. / Actividad antiurolítica del extracto etanólico de propóleo ayacuchano en ratas.

OBJECTIVES: To determine the antiurolytic activity of the ethanolic extract of Ayacuchan propolis in a preventive model of urolithiasis in rats. MATERIALS AND METHODS: A total of 45 male Sprague-Dawley albino rats were studied. The antiurolithic effect was analyzed in five groups of six animals each: blank, control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium chloride), and three experimental groups (treated with the ethanol extract of propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs were administered by orogastric cannulation for 16 days. The diuretic effect was evaluated in 15 rats distributed in five groups: blank, control (treated with furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively). Urinary pH, urinary density, and sedimentation of calcium oxalate were measured. The presence of kidney stones was evaluated by examination of hematoxylin-eosin-stained histopathological sections under polarized light. RESULTS: The ethanolic extract of Ayacuchan propolis caused significant changes in the levels of uric acid, serum lactate dehydrogenase, pH, and urinary density in the three dose groups. The results of histological analysis indicated a lower presence of calcium oxalate crystals in kidney tubular cells in the group treated with 250 mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than that in the control group. CONCLUSIONS: The ethanolic extract of Ayacuchan propolis demonstrated antiurolytic activity in a preventive rat model of urolithiasis.

OBJETIVOS: Determinar la actividad antiurolítica del extracto etanólico de propóleo ayacuchano en un modelo preventivo de urolitiasis inducido en ratas. MATERIALES Y MÉTODOS: Se estudiaron 45 ratas albinas macho Sprague-Dawley. El efecto antiurolítico se analizó en cinco grupos de seis animales: blanco, control (1 mL de etilenglicol al 5% y 1 mL cloruro de amonio al 5%) y tres grupos tratados con el extracto etanólico de propóleo a dosis diaria de 250, 350 y 500 mg/Kg. Las sustancias fueron administradas mediante canulación orogástrica durante 16 días. El efecto diurético se evaluó en 15 ratas distribuidas en cinco grupos: blanco, control (furosemida 20 mg/Kg) y tres grupos tratados con extracto etanólico de propóleo a dosis de 250, 350 y 500 mg/Kg. Se midió el pH urinario, densidad urinaria y sedimentación del oxalato de calcio; la presencia de cálculos renales se evaluó mediante cortes histopatológicos por tinción con hematoxilina-eosina bajo luz polarizada. RESULTADOS: El extracto etanólico de propóleo ayacuchano produjo cambios significativos en los valores de ácido úrico, lactato deshidrogenasa sérico, pH, densidad urinaria al comparar los tres grupos dosis; en el análisis histológico observado a luz polarizada se observó menor presencia de cristales de oxalato de calcio en células tubulares del riñón en el grupo tratado a dosis de 250 mg/Kg; el efecto diurético en el grupo tratado con dosis de 250 mg/kg fue mayor en comparación con la furosemida. CONCLUSIONES: El extracto etanólico de propóleo ayacuchano presenta actividad antiurolítica en el modelo preventivo de urolitiasis en ratas albinas.

The effect of commonly used drugs on angiogenesis.

BACKGROUND: Within the last decade, there has been much interest in the area of tumor angiogenesis, with the advent of many new anti-angiogenic drugs undergoing testing in cancer clinical Phases II and III. Many of the cancer patients also take multiple medications for a variety of chronic illnesses. Because of possible drug-drug interactions, it is important to investigate the effect that commonly prescribed medications may have on angiogenesis. MATERIALS AND METHODS: In this pilot study, we assessed the effect of the following drugs on in vitro angiogenesis: atenolol, diltiazem, enalapril, disopyramide, mexiletine, coumadin, cimetidine and omeprazole. RESULTS & CONCLUSION: We observed that, although some of these drugs at massive doses inhibited endothelial proliferation, they did not affect in vitro angiogenesis at human therapeutic ranges.

Actividad antiurolítica del extracto etanólico de propóleo ayacuchano en ratas / Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats

RESUMEN Objetivos Determinar la actividad antiurolítica del extracto etanólico de propóleo ayacuchano en un modelo preventivo de urolitiasis inducido en ratas. Materiales y métodos Se estudiaron 45 ratas albinas macho Sprague-Dawley. El efecto antiurolítico se analizó en cinco grupos de seis animales: blanco, control (1 mL de etilenglicol al 5% y 1 mL cloruro de amonio al 5%) y tres grupos tratados con el extracto etanólico de propóleo a dosis diaria de 250, 350 y 500 mg/Kg. Las sustancias fueron administradas mediante canulación orogástrica durante 16 días. El efecto diurético se evaluó en 15 ratas distribuidas en cinco grupos: blanco, control (furosemida 20 mg/Kg) y tres grupos tratados con extracto etanólico de propóleo a dosis de 250, 350 y 500 mg/Kg. Se midió el pH urinario, densidad urinaria y sedimentación del oxalato de calcio; la presencia de cálculos renales se evaluó mediante cortes histopatológicos por tinción con hematoxilina-eosina bajo luz polarizada. Resultados El extracto etanólico de propóleo ayacuchano produjo cambios significativos en los valores de ácido úrico, lactato deshidrogenasa sérico, pH, densidad urinaria al comparar los tres grupos dosis; en el análisis histológico observado a luz polarizada se observó menor presencia de cristales de oxalato de calcio en células tubulares del riñón en el grupo tratado a dosis de 250 mg/Kg; el efecto diurético en el grupo tratado con dosis de 250 mg/kg fue mayor en comparación con la furosemida. Conclusiones El extracto etanólico de propóleo ayacuchano presenta actividad antiurolítica en el modelo preventivo de urolitiasis en ratas albinas.

ABSTRACT Objectives To determine the antiurolytic activity of the ethanolic extract of Ayacuchan propolis in a preventive model of urolithiasis in rats. Materials and methods A total of 45 male Sprague-Dawley albino rats were studied. The antiurolithic effect was analyzed in five groups of six animals each: blank, control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium chloride), and three experimental groups (treated with the ethanol extract of propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs were administered by orogastric cannulation for 16 days. The diuretic effect was evaluated in 15 rats distributed in five groups: blank, control (treated with furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively). Urinary pH, urinary density, and sedimentation of calcium oxalate were measured. The presence of kidney stones was evaluated by examination of hematoxylin-eosin-stained histopathological sections under polarized light. Results The ethanolic extract of Ayacuchan propolis caused significant changes in the levels of uric acid, serum lactate dehydrogenase, pH, and urinary density in the three dose groups. The results of histological analysis indicated a lower presence of calcium oxalate crystals in kidney tubular cells in the group treated with 250 mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than that in the control group. Conclusions The ethanolic extract of Ayacuchan propolis demonstrated antiurolytic activity in a preventive rat model of urolithiasis.

Enfrentamiento quirúrgico de la litiasis biliar / Surgical confront of the biliary litiasis

Se presenta un casuística personal de 222 pacientes biliares sintomáticos. Se comunica su estudio preoperatorio, los procedimientos quirúrgicos y sus resultados. Se concluye que la patología biliar es un problema real, que hay un importante grupo de pacientes en los que debe resolverse complicaciones serias. Un buen método de estudio preoperatorio es el criterio clínico radiológico. La colangiografía intraoperatoria de rutina no influye en la prevención de daño de la vía biliar, siempre que se mantengan los principios básicos de la cirugía y, se reconfirman los buenos resultados de la colecistectomía laparoscópica

Secuelas de poliomielitis en la clínica San Juan de Dios de Arequipa / Sequelae steages of polimielytis in the San Juan de Dios of Arequipa

Se realiza el estudio de 17 casos de poliomielitis, en la fase crónica o de secuelas, hospitalizados de junio de 1986 a junio de 1987 en la clínica San Juan de Dios de Arequipa, Perú. Se hace un análisis de su tratamiento quirúrgico en las secuelas de miembros inferiores. no está erradicada la enfermedad y debe proseguirse en su lucha mediante campañas de vacunación permanentes

Cirugía de la enfermedad hemorroidal / Surgery of hemorrhoidal disease

Se presenta la casuística de 173 pacientes operados de enfermedad hemorroidal mediante técnica tipo Milligan y Morgan en nuestro Servicio. La mitad de los pacientes tenía historia de 5 a 10 años de evolución y la mayoría presentaba hemorroides de grados III y IV. En el 75% se practicaron tres colgajos cutáneos - mucosos y en 23%, dos, adicionando fisurectomía, esfinterotomía, criptectomía y ligaduras cuando fue necesario. El promedio de hospitalización fue de 5,8 días y de cicatrización de 39 días. Se presentaron escasas complicaciones precoces y un 4,04% de complicaciones tardías. El 90% de pacientes controlados están asintomáticos. Recomendamos la técnica de Milligan y Morgan por ser sencilla y de baja morbilidad