ABSTRACT

Approximately 90% of confirmed cancer cases annually are reported in low to middle-income countries. In Honduras, the incidence of pediatric cancer has been steadily increasing, accompanied by a higher cancer mortality rate attributed to diagnostic errors, limited access to healthcare, and management challenges. Diagnostic pitfalls, such as failure to recognize signs of malignancy, inadequate assessment of persistent symptoms, and misinterpretation of diagnostic tests, significantly impede effective cancer care. This retrospective case study collected data from 68 pediatric patients diagnosed with Acute Lymphoblastic Leukemia (ALL) at the Honduran Social Security Institute in Tegucigalpa between January 2015 and December 2022. Data retrieval encompassed demographic features, clinical characteristics, and laboratory findings. We used SPSS Statistics version 29.0.2.0 to perform all statistical analysis. The cohort comprised patients of equal gender distribution, with 42.6% (N: 29) belonging to the age group of 1 to 4 years. The hospital diagnosed an average of 8.5 cases each year. Fever was the most prevalent symptom, affecting 80.9% of patients (N: 55). Hemoglobin levels were below 10 mg/dL in 67.6% of patients, with 33.8% exhibiting levels below 7 mg/dL (N: 23) and equal proportion falling within the 7-10 mg/dL range (N: 23). Platelet levels were below 150,000/µL, with 48.5% experiencing severe thrombocytopenia (platelet levels <50,000/µL). Additionally, most patients presented phosphorus levels exceeding 4.5 mg/dl (N: 33, 48.5%), along with elevated LDH levels surpassing 500 U/l (N: 34, P: 50%). The presence of persistent fever should trigger suspicion of cancer, necessitating thorough assessment. Implementing guidelines outlining common symptoms and referral protocols could significantly reduce mortality in Honduran children with ALL.

Aproximadamente el 90% de los casos confirmados de cáncer anualmente se reportan en países de ingresos bajos a medios. En Honduras, la incidencia de cáncer pediátrico ha aumentado, con una mayor mortalidad atribuida a errores de diagnóstico, acceso limitado a la atención médica y desafíos en el manejo. Los errores diagnósticos, como no reconocer signos de malignidad, evaluación inadecuada de síntomas persistentes e interpretación errónea de pruebas diagnósticas, dificultan la atención efectiva del cáncer. Este estudio retrospectivo comprende una muestra de 68 pacientes pediátricos diagnosticados con Leucemia Linfoblástica Aguda (LLA) en el Instituto Hondureño de Seguridad Social en Tegucigalpa entre enero de 2015 y diciembre de 2022. La recopilación de datos incluyó características demográficas, clínicas y hallazgos de laboratorio; con análisis estadístico utilizando SPSS Statistics versión 29.0.2.0. La cohorte comprendía pacientes de igual distribución por género, con el 42.6% (N: 29) perteneciendo al grupo de edad de 1 a 4 años. El hospital diagnosticó un promedio de 8.5 casos cada año. La fiebre fue el síntoma más prevalente, afectando al 80.9% de los pacientes (N: 55). Los niveles de hemoglobina fueron inferiores a 10 mg/dL en el 67.6% de los pacientes, con el 33.8% por debajo de 7 mg/dL (N: 23) y una proporción igual dentro del rango de 7-10 mg/dL (N: 23). Los niveles de plaquetas fueron inferiores a 150,000/µL, con el 48.5% experimentando trombocitopenia severa (niveles de plaquetas <50,000/µL). Además, la mayoría de los pacientes presentaron niveles de fósforo superiores a 4.5 mg/dL (N: 33, 48.5%) y niveles elevados de LDH que superaban los 500 U/L (N: 34, P: 50%). La presencia de fiebre persistente debe despertar sospechas de cáncer, requiriendo una evaluación exhaustiva. La implementación de guías que delineen síntomas comunes y protocolos de referencia podría reducir significativamente la mortalidad en niños hondureños con LLA.

ABSTRACT

A rinite alérgica local (RAL) é um fenótipo de rinite definido recentemente e seu diagnóstico configura um grande desafio tanto para médicos, como para os seus pacientes. A RAL não apresenta evidências de sensibilização sistêmica e, por essa razão, é frequentemente classificada de forma inadequada como uma rinite não alérgica. Este fenótipo de rinite apresenta resposta inflamatória alérgica T2 nasal e síntese local de IgE específica, sendo que o teste de provocação nasal específico é considerado o método padrão ouro para realizar o seu diagnóstico. A RAL possui características clínicas semelhantes aos outros fenótipos de rinite, e pela dificuldade diagnóstica é subdiagnosticada em todas as faixas etárias. O diagnóstico fenotípico correto da rinite tem potenciais benefícios para os pacientes, não apenas por possibilitar a implementação de cuidados para a redução da exposição ambiental aos alérgenos identificados, mas principalmente por permitir a realização de imunoterapia alérgeno específica.

Local allergic rhinitis (LAR) is a recently defined rhinitis phenotype, and its diagnosis represents a major challenge for both physicians and patients. LAR shows no evidence of systemic sensitization and is therefore often inappropriately classified as non-allergic rhinitis. This rhinitis phenotype shows a nasal T2 allergic inflammatory response and local IgE synthesis, and nasal allergen challenge is considered the gold standard method for its diagnosis. LAR has clinical features similar to those of other rhinitis phenotypes, and due to diagnostic difficulties, it is underdiagnosed in all age groups. The correct phenotypic diagnosis of LAR offers potential benefits for patients not only by enabling the implementation of care to reduce environmental exposure to identified allergens, but mainly by allowing allergen-specific immunotherapy.

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Introduction Dendritic cell (DC) vaccines have demonstrated good efficacy in preventing relapse and in increasing survival of patients affected by a variety of both solid and hematological tumors. Most protocols used to generate these cells involve the automated separation of peripheral blood monocytes from patients. This approach requires specialized equipment, which elevates the cost of this type of therapy, potentially limiting the widespread access to patients. Method: In this study, we compare the yield and quality of dendritic cells generated from monocytes and isolated by an automated method or by manual methods using gradient centrifugation. Results The results demonstrate the equivalence of the 3 methods in relation to the yield and final quality of the product, however with considerable differences between the costs of these procedures. In addition, this study also demonstrates the feasibility of the antigenic pulse with autologous tumor cell lysates, constituting a source of antigens, not only easily obtained and manipulated, but also specific to the patient's tumor. Conclusion These findings may have important implications for emerging centers interested in using this medical approach and potentially increase the access of a greater number of patients to this therapeutic option.

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Introducción: La encefalitis por anticuerpos contra el receptor N-metil.D.aspartato (NMDA-R) es un trastorno inflamatorio del sistema nervioso central (SNC) en el cual autoanticuerpos dirigidos hacia la subunidad NR1 del receptor N-metil-D aspartato (NMDA) desarrollan un conjunto de síntomas neuropsiquiátricos, convulsiones y movimientos anormales. El tratamiento recomendado incluye metilprednisolona (MP) y gamaglobulina (IVIg), y/o recambio plasmático terapéutico (RPT); y en caso de no respuesta: rituximab (RTX) y/o ciclofosfamida (CFM). Objetivos: Analizar características clínicas, bioquímicas, electroencefalograma (EEG), resonancia magnética (RM) cerebral, tratamientos recibidos y resultados observados en una serie de pacientes con encefalitis autoinmune (EA) probable o confirmada. Materiales y métodos: Analizamos las historias clínicas de pacientes menores a 17 años que cumplían criterios diagnósticos de Graus (2016) para EA probable, con seguimiento mayor a 6 meses, internados en el Hospital Garrahan entre 2008 y 2023. El diagnóstico se definió por la identificación de anticuerpos anti-NMDAR (N-metil D-aspartato) en líquido cefalorraquídeo (LCR) por ensayo basado en células - cell bassed assay (CBA). Resultados: Reunieron criterios de EA probable 94 pacientes con una edad media de 89.5 meses, 51% mujeres. Se dividieron en dos grupos: seropositivos y seronegativos de acuerdo al resultado del biomarcador. Seropositivos 45/94. El síntoma inicial más frecuente fue: convulsiones. El 28% requirió ingreso a Unidad de Cuidados Intensivos (UCI). 4 pacientes seropositivos y 1 seronegativo tuvieron encefalitis por el virus del herpes simple (Om) previamente. En una paciente seronegativa se diagnosticó teratoma ovárico. Hallazgos de estudios complementarios: LCR patológico en el 29%, RM cerebral en el 52%, EEG en el 74%. El tratamiento de primera línea más empleado fue MP + IVIg. El 46% de los pacientes presentó recuperación completa. Entre los pacientes que recibieron RTX, el 65% tuvo una recuperación completa. Ningún paciente que recibió RTX presentó recaída. Conclusión: Ante la sospecha de EA se debe considerar el inicio temprano de inmunoterapia para favorecer la rápida recuperación funcional. Se recomienda el uso temprano de RTX en los casos con presentación grave o respuesta subóptima al tratamiento de primera línea para beneficiar la respuesta clínica y reducir el riesgo de recaída (AU)

Introduction: Encephalitis due to antibodies against the N-methyl-D-aspartate receptor (NMDA-R) is an inflammatory disorder of the central nervous system (CNS) in which autoantibodies directed against the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor develop a set of neuropsychiatric symptoms, seizures, and abnormal movements. The recommended treatment includes methylprednisolone (MP) and intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE); and in case of non-response: rituximab (RTX) and/or cyclophosphamide (CFM). Objectives: To analyze clinical, biochemical, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, treatments received, and outcomes observed in a series of patients with probable or confirmed autoimmune encephalitis (AE). Materials and methods: We analyzed the medical records of patients under 17 years of age who met Graus' diagnostic criteria (2016) for probable AE, with follow-up of more than 6 months, hospitalized at Hospital Garrahan between 2008 and 2023. Diagnosis was defined by the identification of anti-NMDAR antibodies (N-methyl D-aspartate) in cerebrospinal fluid (CSF) by cell-based assay (CBA). Results: Ninety-four patients met criteria for probable AE with a mean age of 89.5 months, 51% female. They were divided into two groups: seropositive and seronegative according to the biomarker result. Seropositive 45/94. The most frequent initial symptom was seizures. Twenty-eight percent required admission to the Intensive Care Unit (ICU). Four seropositive patients and one seronegative patient had previously had herpes simplex encephalitis (Om). Ovarian teratoma was diagnosed in one seronegative patient. Findings of complementary studies: Pathological CSF in 29%, brain MRI in 52%, EEG in 74%. The most commonly used first-line treatment was MP + IVIg. Forty-six percent of patients experienced complete recovery. Among patients who received RTX, 65% had complete recovery. No patient who received RTX experienced relapse. Conclusion: In the suspicion of AE, early initiation of immunotherapy should be considered to promote rapid functional recovery. Early use of RTX is recommended in cases with severe presentation or suboptimal response to first-line treatment to benefit clinical response and reduce the risk of relapse (AU)

ABSTRACT

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
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γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.

ABSTRACT

BACKGROUND@#The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.@*METHODS@#We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.@*RESULTS@#All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.@*CONCLUSIONS@#Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
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OBJECTIVE@#To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC).@*METHODS@#Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected.@*RESULTS@#Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production.@*CONCLUSIONS@#This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

ABSTRACT

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

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Hepatocellular carcinoma (HCC) is well characterized as a heterogeneous disease. Its late-stage diagnosis and chemotherapy resistance make it one of the refractory tumors in China. Natural killer (NK) cells play a significant role in immune surveillance. However, NK cells become dysfunctional in the progression of HCC, leading to tumor immune escape. This article reviews the recent progress on different strategies of NK cell-based immunotherapy in treating HCC, including direct adoptive NK cell transfer, gene engineering in NK cell, NK cell receptor targeting, immunosuppressive microenvironment modification, and tumor toxicity enhancement by cytokines or traditional Chinese medicine. These NK cell-based strategies have shown promising therapeutic potential.

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Abstract Objectives: to evaluate the effect of oropharyngeal colostrum immunotherapy on the length of hospital stay in preterm newborns with very low birth weight. Methods: interventional ambispective study, which consisted of eight daily administrations of 0.2 ml (four drops) of colostrum, totaling up to 56 syringes (for up to seven days). The control was historic. The main independent variable: length of hospital stay (days). Survival analysis was performed using the Kaplan-Meier Method and the survival effect was estimated - Log Rank Test (Mantel-Cox) and Breslow Test (Generalized Wilcoxon). A significance level of 5% was adopted. Results: of the 109 mother/child pairs, 56 were part of the treatment and 53 were part of the control group. There was no association between oropharyngeal colostrum immunotherapy and length of stay for preterm newborns with very low birth weight in the general sample. However, after stratification, a shorter hospital stay (42 versus 51 days, HR= 1.78, CI95%=1.02-3.09, p=0.04) was demonstrated among premature infants with ≥28 gestational weeks undergoing oropharyngeal colostrum immunotherapy. Conclusions: we found an association between oropharyngeal colostrum immunotherapy and shorter median length of hospital stay in the subgroup of premature infants ≥ 28 weeks of gestational age, but we did not find significant differences in those <28 weeks.

Resumo Objetivos: avaliar o efeito da imunoterapia orofaríngea de colostro no tempo de internamento hospitalar de recém-nascidos pré-termos de muito baixo peso. Métodos: estudo de intervenção, ambispectivo, que consistiu em oito administrações diárias de 0,2 ml (quatro gotas) de colostro, totalizando até 56 seringas (por até sete dias). O controle foi histórico. A variável independente principal: tempo de permanência hospitalar (dias). Realizada análise de sobrevivência pelo Método de Kaplan-Meier e estimado o efeito da sobrevida - Teste de Log Rank (Mantel-Cox) e Teste de Breslow (Wilcoxon Generalizado). Adotou-se o nível de significância de 5%. Resultados: das 109 duplas mães/filho, 56 fizeram parte da análise do grupo tratamento e 53 do controle. Não houve associação entre imunoterapia orofaríngea de colostro e tempo de internamento de recém-nascidos pré-termos de muito baixo peso na amostra geral. Após estratificação demonstrou-se menor tempo de permanência hospitalar (43 versus 51 dias, HR=1,78, IC95%= 1,02-3,09, p=0,04) entre os prematuros com ≥28 semanas gestacionais submetidos a imunoterapia orofaríngea de colostro. Conclusões: encontrou-se associação entre imunoterapia orofaríngea de colostro e menor mediana de tempo de internamento hospitalar no subgrupo de prematuros ≥ 28 semanas de idade gestacional, porém não foram encontradas diferenças significativas naqueles < 28 semanas.

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A sobrevivência ao câncer de mama é um problema de saúde pública que demanda serviços especializados com foco na reabilitação psicossocial. Entre as necessidades identificadas nesse contexto está o incentivo à adoção de estratégias de promoção de autocuidados pelas mulheres. Uma das estratégias adotadas consiste no grupo de apoio psicológico, que auxilia as pacientes a enfrentar a longa jornada do tratamento. Assim, o objetivo deste estudo é compreender os significados produzidos por mulheres com câncer de mama sobre sua participação em um grupo de apoio. Trata-se de um estudo qualitativo, descritivo e exploratório realizado com dez mulheres com câncer de mama usuárias de um serviço de reabilitação para mastectomizadas. Como referencial metodológico foi utilizada a Teoria Fundamentada nos Dados. A coleta de dados foi realizada por meio de entrevista aberta em profundidade e os conteúdos foram transcritos e codificados. A análise indutiva e o método de comparação constante foram aplicados nos processos de codificação aberta, axial e seletiva, que permitiram identificar três categorias nucleares: percepção das atividades realizadas no grupo, identificação de benefícios e barreiras do convívio no grupo e transformações decorrentes da participação. As participantes significaram sua presença no grupo como fonte de acolhimento, apoio, desenvolvimento de recursos pessoais e amizades, contribuindo para promover sua qualidade de sobrevida. Além dos potenciais benefícios, também foram identificadas barreiras que podem dificultar a adesão e continuidade da participação no grupo, o que sugere a necessidade de incorporar no cuidado um olhar para as dimensões subjetivas da saúde da mulher.(AU)

Surviving breast cancer is a public health problem and depends on services focused on psychosocial rehabilitation. Healthcare providers must encourage women to adopt strategies to promote their self-care. The psychological support group is a resource that helps women to face the long journey of treatment. This study aimed to understand the meanings women with breast cancer produced about their participation in a support group. This exploratory cross-sectional study was carried out with 10 women with breast cancer who use a rehabilitation service for mastectomized patients. Grounded Theory was used as a methodological reference. An open in-depth interview was applied for data collection. The contents were transcribed and coded. Inductive analysis and the constant comparison method were applied in the open, axial, and selective coding processes, which enabled the identification of three core categories: perception of the activities carried out in the group, identification of benefits and barriers of living in the group, and transformations resulting from participation. Participants denote their involvement with the group as a source of shelter, support, development of personal resources and friendships that helps promoting quality of life. Besides these potential benefits, participants also evinced barriers that can hinder adherence and continuity of participation in the group, suggesting the importance of incorporating a look at the subjective dimensions of women's health into care.(AU)

Sobrevivir al cáncer de mama es un problema de salud pública que depende de los servicios centrados en la rehabilitación psicosocial. Entre las necesidades identificadas en esta materia se encuentra el uso de estrategias para promover el autocuidado. Uno de los recursos que ayuda a afrontar el largo camino del tratamiento es el grupo de apoyo psicológico. El objetivo de este estudio es conocer los significados que producen las mujeres con cáncer de mama sobre su participación en un grupo de apoyo. Se trata de un estudio cualitativo, descriptivo y exploratorio, realizado con diez mujeres con cáncer de mama usuarias de un servicio de rehabilitación para mastectomizadas. Como referencia metodológica se utilizó la teoría fundamentada en los datos. Se aplicó una entrevista abierta en profundidad para la recogida de datos, cuyos contenidos fueron transcritos y codificados. El análisis inductivo y el método de comparación constante se aplicaron en los procesos de codificación abierta, axial y selectiva, lo que permitió identificar tres categorías centrales: percepción de las actividades realizadas en el grupo, identificación de los beneficios y las barreras de vivir en el grupo y transformaciones resultantes de la participación. Las mujeres denotan su participación en el grupo como una fuente de acogida, apoyo, desarrollo de recursos personales y amistades, que ayuda a promover la calidad de vida. Además de los beneficios potenciales, también se identificaron barreras que pueden dificultar la adherencia y continuidad de la participación en el grupo, lo que sugiere la necesidad de incorporar en la atención una mirada centrada en las dimensiones subjetivas de la salud de las mujeres.(AU)

ABSTRACT

Objetivo: Identificar las barreras de acceso en Colombia al tratamiento intravesical con el bacilo de Calmette-Guérin (BCG) para cáncer de vejiga no invasor de músculo (CVNMI) desde la perspectiva de urólogos y pacientes. Método: Estudio observacional de corte transversal que se ejecutó por medio de la aplicación de una encuesta anónima a urólogos y pacientes en manejo con BCG en Colombia entre enero y junio de 2023 para valorar sus percepciones respecto a esta terapia. Ejecutamos análisis univariable y bivariable para determinar correlaciones entre variables de interés. Resultados: Participaron 83 urólogos y 68 pacientes. Para los urólogos, las razones para descartar el tratamiento con BCG son: ausencia de indicación clínica (36,8%), no disponibilidad del medicamento (17,1%) y falta de rutas asistenciales (17,1%). El 82,8% manifestó que la no disponibilidad y problemas con la dispensación del medicamento son las principales barreras para el tratamiento. Desde la perspectiva de los pacientes, las principales barreras fueron: dispensación/entrega del medicamento (35,2%), no disponibilidad (17,6%) y ausencia de seguimiento clínico (17,6%). El 43,1% no recibió apoyo/seguimiento y el 76% considera que se deben mejorar las rutas de entrega y aplicación de BCG. El carácter y nivel de complejidad de las instituciones hospitalarias, así como el volumen de pacientes/año atendidos con CVNMI fueron factores correlacionados con patrones de prescripción de BCG. Hubo diferencias de percepción entre pacientes sobre la facilidad de acceso al tratamiento y tiempo entre prescripción-administración según la ciudad donde recibieron el tratamiento. Conclusiones: En Colombia existen barreras clínicas, logísticas y administrativas que limitan el adecuado y oportuno acceso al tratamiento con BCG.

Objective: To identify the barriers to access to bacille Calmette-Guérin (BCG) treatment for non-muscle invasive bladder cancer (NMIBC) in Colombia from the perspective of urologists and patients. Method: This observational cross-sectional study was conducted through an anonymous survey administered to urologists and patients undergoing BCG treatment in Colombia between January and June 2023 to assess their perceptions regarding this therapy. We performed univariate and bivariate analyses to determine correlations between variables of interest. Results: A total of 83 urologists and 68 patients participated. For urologists, the reasons for excluding BCG treatment were lack of clinical indication (36.8%), unavailability of the medication (17.1%), and lack of healthcare pathways (17.1%). 82.8% stated that unavailability and problems with the dispensing of the medication are the main barriers to treatment. From the patients' perspective, the main barriers were dispensing/delivery of the medication (35.2%), unavailability (17.6%), and lack of clinical follow-up (17.6%). 43.1% did not receive support or clinical follow-up, and 76% believe that the delivery and administration pathways of BCG need to be improved. The university status and complexity level of the hospitals, as well as the volume of patients/year treated with NMIBC, were factors correlated with BCG prescription patterns. There were differences in patients' perceptions regarding ease of access to treatment and time between prescription and administration depending on the city where they received treatment. Conclusions: In Colombia, there are clinical, logistical, and administrative barriers that limit adequate and timely access to BCG treatment.

ABSTRACT

Pancreatic ductal adenocarcinoma has increased its incidence in recent years. In approximately half of the cases, the diagnosis is made when the disease is in the metastatic stage. In advanced stages, treatment with immunotherapy is included with promising results. Histopathological diagnosis is required for the administra - tion of chemotherapy. Endosonography biopsy has benefits due to its high sensitivity and specificity, absence of the need for hospitalization, and low adverse events. Fine biopsy needles are classified according to two characteristics: diameter (19, 22 and 25 G) and tissue acquisition mechanism (FNA and FNB). The emergence of immunotherapy guided by tumor oncogenetics requires an increase in sample size. There are no significant differences between the presence of the pathologist in taking the sample (rapid on-side evaluation, ROSE) over the macroscopic visualization of the biopsy by the endosonographer (macroscopic on-side evaluation, MOSE). The use of FNB for biopsy is recommended over FNA with ROSE when it is necessary to make a diagnosis or genetic study and it is not possible to perform it with the ROSE modality. The factors that determine an adequate sample collection are the location of the biopsy (pancreas 54.3% vs. lymph nodes/metastasis 76.5%) and the diameter/type of needle.

El adenocarcinoma ductal pancreático ha presentado un aumento de su incidencia en los últimos años En aproximadamente la mitad de los casos se realiza el diagnóstico cuando la enfermedad se encuentra en etapa metastásica. En etapas avanzadas se incluye el tratamiento con inmunoterapia con resultados promisorios. Para la administración de quimioterapia se requiere el diagnóstico histopatológico. La biopsia por endosonografía presenta beneficios debido a su alta sensibilidad y especificidad, ausencia de necesidad de hospitalización y bajos eventos adversos. Las agujas finas de biopsia se clasifican según dos características: diámetro (19, 22 y 25 G) y mecanismo de adquisición del tejido (FNA y FNB). La aparición de la inmunoterapia guiada por la oncogenética tumoral requiere un incremento del tamaño de las muestras. No existen diferencias significativas entre la presencia del anatomopatólogo en la toma de la muestra ( rapid on-side evaluation, ROSE) por sobre la visualización macroscópica de la biopsia por parte del endosonografista (macroscopic on-side evaluation, MOSE). Se recomienda el uso de FNB para toma de biopsia por sobre FNA con ROSE cuando es necesario hacer diagnóstico, estudio genético y no es posible realizarlo con modalidad ROSE. Los factores que determi - nan una toma de muestra adecuada son la localización de la biopsia (páncreas 54,3% vs. linfonodos/metástasis 76,5%) y el diámetro/tipo de aguja

ABSTRACT

Abstract Objectives: to evaluate the effect of oropharyngeal colostrum immunotherapy in reducing cases of late-onset neonatal sepsis in preterm infants with very low birth weight. Methods: this is an intervention study, with a comparative analysis between the incidence of late-onset neonatal sepsis in the treatment group (in use of oropharyngeal colostrum immunotherapy) and the historical control group (newborns monitored in the same intensive care unit prior to the implementation of the oropharyngeal colostrum immunotherapy protocol). 81 premature babies born between 2016 and 2022 participated in the study separated according to whether or not they received oropharyngeal colostrum immunotherapy. The intervention consisted of eight daily applications of 0.2 mL of the mother's own raw colostrum to the newborns oral mucosa during the first seven days of life. Relative Risk and Absolute Risk Reduction and Number needed to Treat were calculated. Results: a protective effect of oropharyngeal colostrum immunotherapy against late neonatal sepsis was noted. Relative Risk: 0.43; CI95% = 0.21-0.91; Absolute Risk Reduction: 0.26; CI95%= 6.51 - 45.92 and Number Needed to Treat: 4 (2.17-15.34). Conclusion: administration of oropharyngeal colostrum proved to be a promising measure in protecting preterm newborns with VLBW against late-onset sepsis.

Resumo Objetivos: avaliar o efeito da Imunoterapia Orofaríngea de Colostro na redução dos casos de sepse neonatal tardia, em recém-nascidos prematuros com muito baixo peso. Métodos: trata-se de um estudo de intervenção, com análise comparativa entre a incidência de sepse neonatal tardia do grupo tratamento (em uso da Imunoterapia Orofaríngea de Colostro) e grupo controle histórico (recém-nascidos acompanhados na mesma unidade de terapia intensiva neonatal, anteriormente à implementação do protocolo de Imunoterapia Orofaríngea de Colostro). Participaram do estudo 81 prematuros nascidos entre 2016 e 2022, separados de acordo com o recebimento ou não da Imunoterapia Orofaríngea de Colostro. A intervenção consistiu em oito aplicações diárias de 0,2 mL de colostro cru da própria mãe na mucosa oral dos participantes, durante os sete primeiros dias de vida. Foi feito cálculo de Risco Relativo e Redução Absoluto de Risco e do Número Necessário para Tratar. Resultados: notou-se efeito protetor da IOC contra a sepse neonatal tardia. Risco relativo: 0,43; IC95%=0,21-0,91; Redução absoluta de risco: 0,26; IC95%=6,51-45,92 e Número necessário para tratar: 4 (2,17-15,34). Conclusão: a administração orofaríngea de colostro se mostrou uma medida promissora na proteção de RN PT com MBP contra sepse tardia.

ABSTRACT

Resumen Las vesículas extracelulares son nanoparticulas secretadas por células procariotas y eucariotas, con funciones variadas que van desde la comunicación intercelular hasta la modulación de la respuesta inmune. La investigación en este tema se enfocó inicialmente en el aislamiento, identificación y caracterización, para luego abarcar los mecanismos fisiológicos en los que se ven involucradas. Más recientemente, la investigación, particularmente centrada en exosomas, ha permitido abrir campo a novedosas hipótesis sobre su utilidad en inmunoterapia y como marcadores biológicos. Esta revisión explora aspectos básicos sobre la biogénesis y la composición de los exosomas, así como su uso en diagnóstico y tratamiento, a partir del conocimiento generado sobre su aislamiento y purificación, distribución de cargos específicos y su relación con la respuesta inmune. Los hallazgos sobre su aplicabilidad en procesos cancerosos son promisorios; sin embargo, existe toda una ventana de posibilidades para investigar esta plataforma molecular como potenciales vacunas acelulares y marcadores de pronóstico, diagnóstico y alerta, tanto en cáncer como en patologías causadas por agentes infecciosos.

Abstract Extracellular vesicles are nanoparticles released by prokaryotic and eukaryotic cells, with a variety of functional roles in intercellular communication and even in modulation of the immune response. Research in this topic was initially focused on isolation, identification and characterization of the vesicles, with subsequent understanding of the physiological mechanisms in which they are involved. Furthermore, recent studies, particularly with exosomes, have opened the field to novel hypotheses about their usefulness in immunotherapy and as biological markers. This review explores general aspects about the biogenesis and composition of exosomes, as well as their potential use in diagnosis and treatment, based on the knowledge generated about their isolation, production, cargoes, delivery engineering and relationship with the immune response. The findings on its applicability in cancerous processes are promising, but there is still a variety of investigation possibilities of this molecular platforms as cell-free vaccines and as prognostic, diagnostic and/or warning markers, both in cancer but also in infectious diseases.

ABSTRACT

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

ABSTRACT

En el último tiempo, la inmunoterapia se ha convertido en una opción terapéutica para diversos tipos de neoplasias, aumentando la sobrevida en muchos casos, pero también los efectos adversos asociados. Existen tres tipos de inmunoterapia utilizados en cáncer: Terapia de células T con receptor de antígeno quimérico (CAR-T), destacando como reacciones adversas el síndrome liberador de citoquinas (CRS) y el síndrome de neurotoxicidad (ICANS); Anticuerpos monoclonales (AcM), cuyos efectos adversos más comunes están relacionados con reacciones de hipersensibilidad; y los Inhibidores de puntos de control inmunitario (ICI) con toxicidad pulmonar claramente reportada. Para un correcto manejo de estas reacciones adversas se requiere un alto índice de sospecha, un adecuado diagnóstico diferencial y un tratamiento oportuno, basado principalmente en corticoides y guiado por criterios de gravedad. Se presenta el caso de un paciente con reacción granulomatosa sarcoidea posterior al uso de Nivolumab.

In recent times, immunotherapy has emerged as a therapeutic option for various neoplasms, significantly improving survival rates in many cases, albeit with associated adverse effects. There are three types of immunotherapy commonly used in cancer treatment: Chimeric Antigen Receptor T-cell Therapy (CAR-T), notable for adverse reactions such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS); Monoclonal Antibodies (mAbs), with the most common adverse effects being hypersensitivity reactions; and Immune Checkpoint Inhibitors (ICI), with well-documented pulmonary toxicity. Adequate management of these adverse reactions requires a high index of suspicion, accurate differential diagnosis, and timely treatment, primarily based on corticosteroids and guided by severity criteria. We present a case of a patient with granulomatous sarcoid-like reaction following the use of Nivolumab.