Latin American Consensus for the Evaluation and Treatment of Patients With Metastatic/Locally Advanced Urothelial Carcinoma.

PURPOSE: Urothelial cancer accounts for approximately 3% of new cancer cases worldwide, with a high burden of disease in countries with medium and low human development indexes where its incidence and mortality are increasing. The purpose of this consensus is to develop statements on the evaluation and treatment of locally advanced and metastatic urothelial carcinoma that would further guide the clinical practice in Latin America. METHODS: A systematic review of the literature was conducted by an independent team of methodologists. Then, a modified Delphi method was developed with clinical specialists from different Latin American countries. RESULTS: Forty-two consensus statements, based on evidence, were developed to address the staging, the evaluation (suitability for chemotherapy, risk assessment, and biomarkers), and systemic treatment (first-line and subsequent therapies) of locally advanced or metastatic urothelial carcinoma. The statements made in this consensus are suggested practice recommendations in the Latin American context; however, the importance of a complete and individualized patient evaluation as a guide for therapeutic selection is highlighted. The availability and affordability of support tools for the evaluation of the disease, as well as specific therapies, may limit the application of the best practices suggested. RECOMMENDATIONS: Therapeutic decisions need to be tailored to the context-specific clinical setting and availability of resources. Local research is promoted to improve outcomes for patients with this challenging cancer in Latin America.

Impact of healthcare inequities on survival in Mexican patients with metastatic renal cell carcinoma.

Introduction: The survival of patients with metastatic renal cell carcinoma (mRCC) has improved dramatically due to novel systemic treatments. However, mRCC mortality continues to rise in Latin America. Methods: A retrospective, multicenter study of patients diagnosed with mRCC between 2010-2018 in Mexico City was conducted. The aim of the study was to evaluate the impact of healthcare insurance on access to treatment and survival in patients with mRCC. Results: Among 924 patients, 55.4%, 42.6%, and 1.9% had no insurance (NI), social security, (SS) and private insurance (PI), respectively. De novo metastatic disease was more common in NI patients (70.9%) compared to SS (47.2%) and PI (55.6%) patients (p<0.001). According to IMDC Prognostic Index, 20.2% were classified as favorable, 49% as intermediate, and 30.8% as poor-risk disease. Access to systemic treatment differed by healthcare insurance: 36.1%, 99.5%, and 100% for the NI, SS, and PI patients, respectively (p<0.001). NI patients received fewer lines of treatment, with 24.8% receiving only one line of treatment (p<0.001). Median overall survival (OS) was 13.9 months for NI, 98.9 months for SS, and 147.6 months for NI patients (p<0.001). In multivariate analysis, NI status, brain metastases, sarcomatoid features, bone metastases, no treatment were significantly associated with worse OS. Conclusion: OS in mRCC was affected by insurance availability in this resource-limited cohort of Mexican patients. These results underscore the need for effective strategies to achieve equitable healthcare access in an era of effective, yet costly systemic treatments.

Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy.

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.

Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma

Background: Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV). Material and Methods: Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model. Results: After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019). Conclusions: Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16.(AU)

Which Larynx-Preservation Strategy Would Be Best for a Patient With Resectable, Locally Advanced, Hypopharynx Squamous Cell Carcinoma?

LP strategies should be considered only in patients with resectable stage III/IV larynx and hypopharynx SCC, ideally those who have a functional larynx. The choice of treatment must be discussed by a multidisciplinary team, and the patient must have an active role in making the decision. CRT and IC-RT are both approved larynx-preservation approaches. IC-RT has demonstrated high rates of LP without decreasing DFS or OS, compared with surgery. CRT has demonstrated better LP rates, as well as local control and LRC, compared with IC-RT, and it should be considered a standard of care.

Las distorsiones cognitivas y el riesgo de suicidio en una muestra de adolescentes chilenos y colombianos: un estudio descriptivo-correlacional / Cognitive distortions and risk for suicidal behaviors, considering Chilean and Colombian adolescents as sample: A descriptive-correlational study is conducted

Resumen Objetivo: Determinar la relación entre las distorsiones cognitivas y el riesgo de suicidio en una muestra de adolescentes chilenos y colombianos. Método: Este es un estudio descriptivo correlacional, de corte no experimental y transversal. El riesgo de suicidio se estableció con la Escala de Suicidalidad de Okasha y se identificaron las distorsiones cognitivas mediante el Inventario de Pensamientos Automáticos de Ruiz y Lujan. Ambas pruebas se realizaron en una muestra de adolescentes chilenos (n = 200; Colegio Alma Mater) y colombianos (n = 200; Institución Educativa Santa Librada) entre los 13 y 18 años de edad. Se seleccionó la muestra mediante un muestreo no probabilístico e intencional, y los participantes se separaron en grupo con riesgo de suicidio y grupo sin riesgo de suicidio (control). Se realizó un análisis descriptivo de la muestra, y una comparación de las distorsiones cognitivas entre los grupos. Finalmente, el análisis inferencial de los datos identificó la relación e intensidad entre distorsiones cognitivas y riesgo de suicidio. Resultados: Se encontró relación estadísticamente significativa entre las distorsiones cognitivas y riesgo de suicidio, y las siguientes distorsiones presentaron la mayor intensidad en chilenos y colombianos: Filtraje, Interpretación del Pensamiento, Pensamiento Polarizado y Sobregeneralización. La correlación entre los resultados de adolescentes chilenos y colombianos es positiva y alta. Conclusiones: Los resultados del presente estudio permitirán prevenir el riesgo de suicidio en adolescentes chilenos y colombianos mediante la evaluación de estas distorsiones cognitivas, las que también podrán guiar intervenciones psicoterapéuticas reduciendo significativamente la severidad y riesgo de cometer suicidio.

Abstract Objective: This paper aims to determine the relationship between cognitive distortions and risk for suicidal behaviors considering Chilean and Colombian adolescents as sample. Method: A descriptive-correlational, non-experimental and transversal study was conducted. The risk of suicide was assessed with screening scale of suicidality (scale of Okasha) and the cognitive distortions were determined through Automatic Thoughts Inventory by Ruiz and Lujan. Both of the tests were performed in Chilean (n = 200; from Alma Mater School) and Colombian adolescents as sample (n = 200; educational institution Santa Librada). These adolescents were between 13-18 years-old. This sample was selected through non-probabilistic intentional sample procedure, and the individuals were divided in two groups: one of them are at risk of suicide and the other without suicidal risk (control). A descriptive analysis of the sample, as well as a comparison of the cognitive distortions between groups was performed. Finally, inferential analysis of data is used to determine the relationship and the intensity between cognitive distortions and the risk for suicidal behaviors. Results: A significant relationship between the cognitive distortions and the suicide risk was found, and the following presented the highest intensity between Chilean and Colombian individuals: Filtration, Interpretation of Though, Polarized Though and Overgeneralization). Moreover, the relationship between the results in Chilean and Colombian adolescents was positive and strong. Conclusions: Results of this study will allow to prevent risk for suicidal behaviors in Chilean and Colombian adolescents, assessing these cognitive distortions, which make possible to conduct psychotherapeutic interventions significantly, reducing the risk for suicidal behaviors.

A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma.

Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, MMP19, apolipoprotein L6, C-X-C motif chemokine ligand (CXCL)8, basic, immunoglobulin-like variable motif containing and CXCL16. These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.

Distribución y susceptibilidad antifúngica de especies de Candida aisladas de hemocultivos en el Hospital del Niño del 2009 al 2010

El incremento en los últimos 10 años de los episodios de candidemia, la identificación de especies inusuales de Candida usando sistemas fenotípicos, la resistencia intrínseca y emergente en aislados clínicos a distintos antifungicos son elementos que nos conducen a realizar identificaciones más precisas y conocer los perfiles de susceptibilidad de las especies de Candida asociadas a fungemias. Objetivo: Realizamos una caracterización genotípica y fenotípica de los aislados clínicos de levaduras procedentes de muestras de hemocultivos de pacientes hospitalizados en el Hospital del Niño del periodo 2009 al 2010, para determinar la frecuencia de distribución las especies de Candida asociadas a fungemia y sus respectivos perfiles de susceptibilidad. Material y método: Se recolectaron un total de 55 cepas de Candida spp y levaduras relacionadas. Sólo se incluyó pacientes hospitalizados con hemocultivos positivos cuyo agente etiológico fueran levaduras y un sólo episodio por paciente, en las salas de Hemato-Oncología , Neonatología, Quemados, Medicina 6 y la Unidad de Terapia Intensiva del Hospital del Niño en el periodo de mayo 2009 a 2010. Se evaluaron 55 cepas, las cuales fueron identificadas usando el Vitek2, la prueba pagar harina de maíz y el método de PCR fingerprinter. Los patrones de bandas de los aislados clínicos fueron comparados con cepas de referencia para confirmar las identificaciones fenotípicas. Se realizaron pruebas de susceptibilidad para 6 antifúngicos de uso sistémico. Resultados: La distribución global final fue la siguiente: complejo de Candida parapsilosis (40%), Candida tropicalis (29.1%), Candida albicans (20%) Candida guilliermondi (3.6%), Sporobolomyces salmonicolor (1.8%), Saccharomyces cerevisiae (1.8%) y complejo Candida haemulonii (3.6%). Las especies del complejo C.parapsilolis presentó 6.3% resistencia a caspofungina y a itraconazol, mientras que C.albicans resultó con 18.2% de resistencia a caspofungina y anfotericina B, y 9.1% de resistencia a fluconazol, itraconazol y voriconazol. Algunas cepas de C.albicans fueron resistentes a varios antifúngicos. Conclusiones: A pesar de las limitaciones del sistema bioquímico automatizado Vitek2, resulta una herramienta útil para la identificación de los aislados clínicos de Candida app. Las pruebas de susceptibilidad usando el método de difusión con pagar Mullër Hinton dosificado resultó altamente confiable y reproducible. Candida parapsilosis fue la causa de fungemia en el Hospital del Niño durante el periodo de estudio. La resistencia a los distintos antifúngicos de los aislados clínicos de Candida spp. no excedió el 10% excepto por caspofungina.

Introduction: The increase in the last 10 years of episodes of candidemia, identification of unusual Candida species using phenotypic systems, intrinsic and emerging resistance in clinical isolates are different anti fungal elements that lead us to make more accurate identifications and knowing the profiles susceptibility of Candida species associated fungemia. Objetive: We do a genotypic and phenotypic characterization of clinical isolates of yeasts from blood cultures of hospitalized patients in the Hospital del Niño period 2009 to 2010 to determine the frequency distribution of Candida species associated with fungemia and their respective profiles susceptibility. Methods: A total of 55 strains of Candida spp and related yeasts were collected. Only hospitalized patients with positive blood cultures whose etiologic agent were yeasts and one episode per patient, in the halls of Hematology - Oncology, Neonatology, Burned, Medicine 6 and the Intensive Care Unit at Hospital del Niño between May 2009 included 2010. The 55 strains were evaluated, which were identified using the VItek2 system, Cornmeal agar test and PCR method fingerprinter. The banding patterns of clinical isolates were compared with reference strains to confirm phenotypic identifications. Susceptibility test were performed for 6 anti fungal for systemic use. Results: The global final distribution was as follows: Candida parapsilosis complex (40%), Candida tropical (29.1%), Candida albinas (20%), Candida gulliermondi (3.6%), Sporobolomyces salmonicolor (1.8%), Saccharomyces cerevisiae (1.8%), Candida complex haemulonii (3.6%). C.parapsilosis complex species showed 77.3% resistance to caspofungin and itraconazole 4.3%; C.tropicalis presented 6.3% resistance to caspofungin and itraconazole while C.albicans resulted with 18.2% resistance to caspofungin and amphotericin B, and 9.1% resistance to fluconazole, itraconazole and voriconazole. Some strains of C.albicans were resistance to several antifungal. Conclusions: Despite the limitations of automated biochemistry Vitek2 system, is a useful tool for identifying clinical isolates of Candida spp. Susceptibility tests using the agar diffusion method was dosed Muller Hinton highly reliable and reproducible. Candida parapsilosis was the main cause of fungemia in the Hospital del Niño during the study period. Resistance to antifungal different clinical isolates of Candida spp did not exceed 10% except for caspofungin.

High clustering rates of multidrug-resistant Mycobacterium tuberculosis genotypes in Panama.

BACKGROUND: Tuberculosis continues to be one of the leading causes of death worldwide and in the American region. Although multidrug-resistant tuberculosis (MDR-TB) remains a threat to TB control in Panama, few studies have focused in typing MDR-TB strains. The aim of our study was to characterize MDR Mycobacterium tuberculosis clinical isolates using PCR-based genetic markers. METHODS: From 2002 to 2004, a total of 231 Mycobacterium tuberculosis isolates from TB cases country-wide were screened for antibiotic resistance, and MDR-TB isolates were further genotyped by double repetitive element PCR (DRE-PCR), (GTG)5-PCR and spoligotyping. RESULTS: A total of 37 isolates (0.85%) were resistant to both isoniazid (INH) and rifampicin (RIF). Among these 37 isolates, only two (5.4%) were resistant to all five drugs tested. Dual genotyping using DRE-PCR and (GTG)5-PCR of MDR Mycobacterium tuberculosis isolates revealed eight clusters comprising 82.9% of the MDR-TB strain collection, and six isolates (17.1%) showed unique fingerprints. The spoligotyping of MDR-TB clinical isolates identified 68% as members of the 42 (LAM9) family genotype. CONCLUSION: Our findings suggest that MDR Mycobacterium tuberculosis is highly clustered in Panama's metropolitan area corresponding to Panama City and Colon City, and our study reveals the genotype distribution across the country.

Infecciones durante la internación de pacientes con cirrosis hepática / Infections during the hospitalization of patients with liver cirrhosis

Se estudiaron retrospectivamente las Historias Clínicas de 291 pacientes con cirrosis hepática internados (etiología alcohólica en el 95//), de los cuales 114 presentaron episodios de infección con 155 episodios en 144 hospitalizaciones. En comunicación previa observamos que la infección fue el cuarto motivo de ingreso y la principal causa de muerte. La incidencia fue mayor en el sexo femenino. Al momento del diagnóstico: 57// correspondía al Child C; 30// presentaron sepsis y 22// fueron de adquisición intrahospitalaria. Las infecciones más frecuentes fueron la P.B.E. y las pulmonares. Se obtuvo documentación bacteriológica en el 55// de los episódios con predominio de bacilos gramnegativos (E. coli), con alta frecuencia relativa de neumococos. Las complicaciones estuvieron relacionadas con la insuficiencia hepática. La mortalidad global fue del 27.1//, mientras que en las intrahospitalarias fue del 42.1// y los pacientes con Child C, 40.9//. Las bacteriemias sin foco y las P.B.E. presentaron la mayor mortalidad. La sobrevida global fue del 42// a los 2 años y del 18// a los 5 años. En conclusión, destacamos la importancia de investigar la presencia de infección en forma sistemática en los pacientes cirróticos con encefalopatía y/o insuficiencia renal sin causa que las justifique

Infecciones durante la internación de pacientes con cirrosis hepática / Infections during the hospitalization of patients with liver cirrhosis

Se estudiaron retrospectivamente las Historias Clínicas de 291 pacientes con cirrosis hepática internados (etiología alcohólica en el 95//), de los cuales 114 presentaron episodios de infección con 155 episodios en 144 hospitalizaciones. En comunicación previa observamos que la infección fue el cuarto motivo de ingreso y la principal causa de muerte. La incidencia fue mayor en el sexo femenino. Al momento del diagnóstico: 57// correspondía al Child C; 30// presentaron sepsis y 22// fueron de adquisición intrahospitalaria. Las infecciones más frecuentes fueron la P.B.E. y las pulmonares. Se obtuvo documentación bacteriológica en el 55// de los episódios con predominio de bacilos gramnegativos (E. coli), con alta frecuencia relativa de neumococos. Las complicaciones estuvieron relacionadas con la insuficiencia hepática. La mortalidad global fue del 27.1//, mientras que en las intrahospitalarias fue del 42.1// y los pacientes con Child C, 40.9//. Las bacteriemias sin foco y las P.B.E. presentaron la mayor mortalidad. La sobrevida global fue del 42// a los 2 años y del 18// a los 5 años. En conclusión, destacamos la importancia de investigar la presencia de infección en forma sistemática en los pacientes cirróticos con encefalopatía y/o insuficiencia renal sin causa que las justifique (AU)

Diagnóstico serológico de infecciones respiratorias por Mycoplasma pneumoniae en niños de 0-5 años / Serologic diagnostic of respiratories infections by Mycoplasma pneumoniae in children of 0-5 years

Se estudió la presencia de anticuerpos contra Mycoplasma pneumoniae en infecciones respiratorias de 20 niños entre 6 meses y 5 años de edad, usando las pruebas serológicas de Fijación de Complemento (FC), Inhibición Metabólica (IM) e Inmunofluorescencia Indirecta (IFI). Se pudo observar seroconversión en 6 niños lo que demuestra que el diagnóstico serológico es un recurso utilizable

Primer aislamiento de Mycoplasma pneumoniae en Panamá / First isolation of Mycoplasma pneumoniae in Panama

Por primera vez en Panamá fue aislado e identificado el Mycoplasma pneumoniae, como agente causal de neumonía, en una niña de 9 años de edad, utilizando el medio de cultivo SP4. Se obtuvieron títulos altos de crioaglutininas (1:2048) en suero y se detectó la producción de anticuerpos contra este microorganismo, por medio de la inmunofluorescencia indirecta. También se realizó la prueba de hibridación del ADN (metodología Gen-Probe)