Globalization of a telepathology network with artificial intelligence applications in Colombia: The GLORIA program study protocol.

In Colombia, cancer is recognized as a high-cost pathology by the national government and the Colombian High-Cost Disease Fund. As of 2020, the situation is most critical for adult cancer patients, particularly those under public healthcare and residing in remote regions of the country. The highest lag time for a diagnosis was observed for cervical cancer (79.13 days), followed by prostate (77.30 days), and breast cancer (70.25 days). Timely and accurate histopathological reporting plays a vital role in the diagnosis of cancer. In recent years, digital pathology has been globally implemented as a technological tool in two main areas: telepathology (TP) and computational pathology. TP has been shown to improve rapid and timely diagnosis in anatomic pathology by facilitating interaction between general laboratories and specialized pathologists worldwide through information and telecommunication technologies. Computational pathology provides diagnostic and prognostic assistance based on histopathological patterns, molecular, and clinical information, aiding pathologists in making more accurate diagnoses. We present the study protocol of the GLORIA digital pathology network, a pioneering initiative, and national grant-approved program aiming to design and pilot a Colombian digital pathology transformation focused on TP and computational pathology, in response to the general needs of pathology laboratories for diagnosing complex malignant tumors. The study protocol describes the design of a TP network to expand oncopathology services across all Colombian regions. It also describes an artificial intelligence proposal for lung cancer, one of Colombia's most prevalent cancers, and a freely accessible national histopathological image database to facilitate image analysis studies.

PD-L1 expression in non-small cell lung carcinoma in Latin America: a systematic review and meta-analysis.

Background: Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is a crucial factor in predicting responses to immunotherapy. This systematic review and meta-analysis focuses on the prevalence of PD-L1 expression and clinicopathological features among Hispanic/Latino (H/L) populations. Methods: Embase, LILACS, Medline, and Virtual Health Library were searched for studies that evaluated the prevalence of PD-L1 in H/L patients. The protocol was submitted to PROSPERO with ID CRD42023488547. We employed the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses to assess the methodological quality and applicability of the included studies. Meta-analyses were done to determine the prevalence using a random effects model. Results: The meta-analysis, encompassing 21 articles with 16,486, revealed that 80.2% of patients had PD-L1 expression data available (n=13,222). The prevalence calculated of PD-L1 expression in Latino NSCLC patients was 55% [95% confidence interval (CI): 0.54-0.55], with 31% (95% CI: 0.27-0.36) showing a tumoral proportion score (TPS) of 1-49%, and 23% (95% CI: 0.16-0.30) registering a TPS ≥50%. Higher expression was observed in male gender, smoking, adenocarcinoma subtypes, poor tumor differentiation, and advanced stages. PD-L1 expression was most frequent in EGFR wild-type status (82.5%) with a odds ratio (OR) 1.54 (95% CI: 1.24-1.92) and PD-L1 expression was associated with ALK positive (OR =1.54; 95% CI: 1.24-1.92). Conclusions: This meta-analysis provides a comprehensive overview of PD-L1 expression in NSCLC in the H/L population. The findings underscore the significant prevalence of PD-L1 expression and emphasize the relevance of immunotherapy in this population. Understanding the clinicopathological features associated with PD-L1 expression can contribute to tailored treatment strategies for NSCLC in Latin America.

Colombian consensus for the molecular diagnosis of endometrial cancer / Consenso colombiano para el diagnóstico molecular del cáncer de endometrio.

Objective: The Cancer Genome Atlas research program (TCGA) developed the molecular classification for endometrial cancer with prognostic and therapeutic utility, which was replaced by the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification by consensus and international guidelines due to its high cost. This article aims to present national recommendations from an expert consensus that allows unification and implementation of the molecular classification for women with endometrial cancer nationwide, with a rational use of resources and technology. Methods: Consensus of 36 experts in clinical oncology, oncological gynecology, pathology, and genetics, with clinical practice in the national territory. The leader group performed a literature review and structuring of questions rated 1 to 9 points. A modified nominal group technique was used. There was a face-to-face meeting with master presentations, deliberative dialogue, and Google Forms (Google LLC, Mountain View, CA, USA) questionnaire voting with analysis and discussion of responses. The non-consensual responses led to a second round of voting. The final manuscript was finally prepared and revised. Results: Seven recommendations were formulated integrating the panelist responses based on evidence, but adjusted to the Colombian context and reality. Recommendation 1. The molecular classification is recommended in all the endometrial cancers using the immunohistochemistry markers as subrogated results from the molecular profile initially proposed in the TCGA classification. Recommendation 2. The sequential test strategy is recommended, starting with the immunohistochemistry markers (p53, MLH1, MSH 2, MSH6, PMS2) simultaneously in all the patients, defining to request POLE (DNA polymerase epsilon) (if available) according to the risk classification based on the surgical piece. Recommendation 3. It is recommended, that the gynecologist oncologist should be the one to request the POLE (if available) according to the final pathology report. This test must be requested for all endometrial cancers stage I-II, except in low risk (stage IA low grade endometrioid histology without linfovascular invasion normal p53) and, stages III-IV without residual disease, without affecting the request of subrogated immunohistochemistry molecular markers upon histology. The consensus proposes that the POLE is requested after the immunohistochemistry and according to the categories in the risk classification established by the 2020 ESGO/ESTRO/ESP guidelines. Recommendation 4. It is recommended to perform immunohistochemistry for hormonal receptors for all women with endometrial cancer and the HER2 in patients with p53abn, simultaneously with the others immunohistochemistry markers. Recommendation 5. It is recommended to perform the immunohistochemistry markers (p53, MLH1, MSH2, MSH6 y PMS2) in an initial endometrial biopsy or curettage when the specimen is adequate and available. In case the initial immunohistochemistry is inconclusive, or there are histological discrepancies between the initial and definitive pathology, it is recommended to repeat the molecular profile in the surgical pathology. The immunohistochemistry markers must be reported in the pathology report according to the CAP (College of American Pathologists) recommendations, independently of the type of sample. Recommendation 6. It is recommended to perform MLH1 promoter methylation testing in patients who exhibit loss of expression of MLH1 in immunohistochemistry whether it is accompanied or not with loss of expression of PMS2. All the patients with deficient MMR (mismatch repair), should be sent for genetic counseling to rule out Lynch syndrome. Recommendation 7. It is recommended to consider the molecular classification in addition to the classical histopathological criteria when making adjuvant judgments, as incorporated by the classification of prognostic groups of the 2020 ESGO/ESTRO/ESP guidelines. Conclusions: It is necessary to implement the molecular classification of endometrial cancer in clinical practice in accordance to the Colombian context, due to its prognostic and probably predictive value. This will enable the characterization of the Colombian population in order to offer individualized guided treatments. This is an academic and nonregulatory document.

Objetivos: el programa Cancer Genome Atlas Research (TCGA) desarrolló la clasificación molecular para cáncer endometrial con utilidad pronóstica y terapéutica, la cual ha sido reemplazada por consensos y guías internacionales por la clasificación ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) debido a su alto costo. El objetivo de este artículo es presentar recomendaciones a nivel nacional derivadas de un consenso de expertos que permitan unificar e implementar la clasificación molecular para mujeres con cáncer endometrial, mediante un uso racional de recursos y tecnología. Materiales y métodos: consenso de 36 expertos en oncología clínica, ginecología oncológica, patología y genética con práctica clínica en el territorio nacional. El grupo líder realizó una revisión de la literatura y estructuración de preguntas calificadas de 1 a 9 puntos. Se utilizó la técnica de grupo nominal modificada. Se efectuaron reuniones presenciales con presentaciones magistrales, diálogo deliberativo y votación de cuestionario Google Forms (Google LLC, Mountain View, CA, USA) con análisis y discusión de respuestas. Las respuestas no consensuadas se llevaron a una segunda ronda de votación. Finalmente, se elaboró y revisó el manuscrito final. Resultados: se formularon siete recomendaciones integrando las respuestas de las panelistas basadas en evidencia, pero ajustadas al contexto y a la realidad colombiana. Recomendación 1. Se recomienda realizar la clasificación molecular en todos los carcinomas endometriales utilizando los marcadores de inmunohistoquímica como resultados subrogados del perfil molecular inicialmente propuesto en la clasificación del TCGA. Recomendación 2. Se recomienda la estrategia secuencial de testeo iniciando por los marcadores de inmunohistoquímica (p53, MLH1, MSH 2, MSH6, PMS2) simultáneamente en todas las pacientes, y definir la solicitud del POLE (polimerasa épsilon del DNA) (si se encuentra disponible) de forma diferida de acuerdo con la clasificación de riesgo basado en la pieza quirúrgica. Recomendación 3. Se recomienda que sea el ginecólogo oncólogo quien solicite el POLE (si se encuentra disponible) de acuerdo con el reporte de patología definitivo. Esta prueba se debe solicitar a todos los cánceres endometriales de estadio I-II, excepto los de bajo riesgo (estadio IA endometrioide de bajo grado sin invasión linfovascular p53 normal) y estadio III-IV sin enfermedad residual, sin afectar la solicitud de los marcadores moleculares subrogados por inmunohistoquímica de acuerdo con la histología. El consenso propone que la solicitud del POLE se realice posterior a la inmunohistoquímica y de acuerdo con la clasificación del riesgo según las categorías establecidas por la guía ESGO/ESTRO/ESP del 2020. Recomendación 4. Se recomienda realizar simultáneamente con los otros marcadores de inmunohistoquímica la prueba para receptores hormonales en todas las pacientes con cáncer endometrial y el HER2 en pacientes con p53abn. Recomendación 5. Se recomienda que los marcadores de inmunohistoquímica (p53, MLH1, MSH2, MSH6 y PMS2) se realicen en la biopsia/legrado endometrial inicial cuando la muestra es adecuada y está disponible. En caso de inmunohistoquímica inicial no concluyente, o discrepancias histológicas entre la patología inicial y definitiva, se recomienda repetir el perfil molecular en la patología quirúrgica. Los marcadores de inmunohistoquímica deben reportarse en el informe de patología de acuerdo con las recomendaciones del CAP (College of American Pathologists), independientemente del tipo de muestra. Recomendación 6. Se recomienda realizar estudio de metilación de promotor de MLH1 en pacientes con pérdida de expresión de MLH1 en la inmunohistoquímica, acompañado o no de pérdida de expresión de PMS2. Todas las pacientes con déficit de MMR (mismatch repair), deben ser enviadas a genética para descartar síndrome de Lynch. Recomendación 7. Se recomienda tener en cuenta la clasificación molecular, además de los criterios histopatológicos clásicos para la toma de decisiones de adyuvancia, tal como los incorpora la clasificación de los grupos pronósticos de la guía ESGO/ ESTRO/ESP del 2020. Conclusiones: es necesario implementar la clasificación molecular de cáncer de endometrio en la práctica clínica acorde al contexto colombiano, dado su valor pronóstico y posiblemente predictivo. Esto permitirá la caracterización de la población colombiana para ofrecer tratamientos guiados de manera individualizada. Se trata de un documento académico y no regulatorio.

The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives.

Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.

Crossing the Andes: Challenges and opportunities for digital pathology in Latin America.

The most widely accepted and used type of digital pathology (DP) is whole-slide imaging (WSI). The USFDA granted two WSI system approvals for primary diagnosis, the first in 2017. In Latin America, DP has the potential to reshape healthcare by enhancing diagnostic capabilities through artificial intelligence (AI) and standardizing pathology reports. Yet, we must tackle regulatory hurdles, training, resource availability, and unique challenges to the region. Collectively addressing these hurdles can enable the region to harness DP's advantages-enhancing disease diagnosis, medical research, and healthcare accessibility for its population. Americas Health Foundation assembled a panel of Latin American pathologists who are experts in DP to assess the hurdles to implementing it into pathologists' workflows in the region and provide recommendations for overcoming them. Some key steps recommended include creating a Latin American Society of Digital Pathology to provide continuing education, developing AI models trained on the Latin American population, establishing national regulatory frameworks for protecting the data, and standardizing formats for DP images to ensure that pathologists can collaborate and validate specimens across the various DP platforms.

Novel influenza A viruses in pigs with zoonotic potential, Chile.

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population. Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains. These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.IMPORTANCEIn the global context, where swine serve as crucial intermediate hosts for influenza A viruses (IAVs), this study addresses the pressing concern of the zoonotic potential of novel reassortant strains. Conducted on a large scale in Chile, it presents a comprehensive account of swine influenza A virus diversity, covering 93.8% of the country's industrialized swine farms. The findings reveal eight distinct swine IAV genotypes, all carrying a complete internal gene cassette of pandemic H1N1 2009 origin, emphasizing potential increased replication and transmission fitness. Genetic divergence of H1N2 and H3N2 IAVs from globally reported strains raises alarms, with evidence suggesting introductions from human seasonal viruses since the mid-1980s. A detailed serological analysis underscores the zoonotic threat, indicating susceptibility in the general population to swine H3N2 and a lack of protective antibodies in vulnerable demographics. These data highlight the importance of continuous surveillance, providing crucial insights for global health organizations.

Gliomas difusos en áreas elocuentes: avances diagnósticos y terapéuticos / Diffuse gliomas within eloquent areas: diagnostic and therapeutic advances

Objetivo: presentar los avances diagnósticos, moleculares y radiológicos, así como en las estrategias terapéuticas para gliomas difusos en los últimos 5 años (2018-2023) en la Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia. Materiales y métodos: se describen las técnicas diagnósticas y terapéuticas utilizadas para gliomas difusos con casos ilustrativos. Resultados: se muestran los avances de las herramientas diagnósticas y terapéuticas para el manejo de gliomas difusos. Discusión: en los últimos 5 años se ha avanzado en la clasificación, diagnóstico y tratamiento de los gliomas difusos, gracias a los avances tecnológicos como los marcadores moleculares, la tractografía y la fusión de imágenes para la neuronavegación y las técnicas de estimulación cortical. Esto ha permitido que el tratamiento de los pacientes con dichos tumores mejore la tasa de morbilidad, la calidad de vida libre de enfermedad y la supervivencia global. Conclusiones: las técnicas de diagnóstico como la tractografía, la fusión integral de imágenes intraoperatorias y el mapeo cerebral electrofisiológico con estimulación cortical y subcortical han mejorado el diagnóstico y tratamiento de los gliomas difusos.

Objective: to present the diagnostic, molecular, radiological, and therapeutic advances, to address diffuse gliomas, made at Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia, in the last 5 years (2018-2023). Materials and methods: diagnostic and therapeutic techniques to address diffuse gliomas are described through illustrative cases. Results: the advances in diagnostic and therapeutic tools for managing diffuse gliomas, are shown. Discussion: in the last 5 years progress in characterizing, diagnosing, and treating diffuse gliomas, thanks to technological breakthroughs, such as molecular markers, tractography, image fusion for neuronavigation, and cortical stimulation techniques, has been achieved. This has allowed improving morbidity rate, disease-free quality of life and overall survival through the treatment provided to patients afflicted with gliomas. Conclusions: Diagnostic techniques based on tractography, comprehensive intraoperative image fusion, and electrophysiological brain mapping with cortical and subcortical stimulation, have improved the diagnostic and therapeutic approaches for diffuse gliomas.

Cross-species transmission and PB2 mammalian adaptations of highly pathogenic avian influenza A/H5N1 viruses in Chile.

H5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human. Between December 9, 2022 - March 14, 2023, a coordinated government/academic response detected HPAIV by real-time RT-PCR in 8.5% (412/4735) of samples from 23 avian and 3 mammal orders. Whole-genome sequences obtained from 77 birds and 8 marine mammals revealed that all Chilean H5N1 viruses belong to lineage 2.3.4.4b and cluster monophyletically with viruses from Peru, indicating a single introduction from North America into Peru/Chile. Mammalian adaptations were identified in the PB2 segment: D701N in two sea lions, one human, and one shorebird, and Q591K in the human and one sea lion. Minor variant analysis revealed that D701N was present in 52.9 - 70.9% of sequence reads, indicating the presence of both genotypes within hosts. Further surveillance of spillover events is warranted to assess the emergence and potential onward transmission of mammalian adapted H5N1 HPAIV in South America.

Cross-protection of commercial vaccines against Chilean swine influenza A virus using the guinea pig model as a surrogate.

Influenza A virus poses a significant threat to public health and the swine industry. Vaccination is the primary measure for controlling the disease, but the effectiveness of vaccines can vary depending on the antigenic match between vaccine strains and circulating strains. In Chile, H1N1pdm09 and other lineages H1N2 and H3N2 have been detected in pigs, which are genetically distinct from the strains included in commercial vaccines. This study aimed to evaluate the cross-protection by commercial vaccines against strains circulating in Chile using the guinea pig model. For this study, four circulating strains [A/swine/Chile/H1A-7/2014(H1N2), A/swine/Chile/H1B-2/2014(H1N2), A/swine/Chile/H1P-12/2015(H1N1), and A/swine/Chile/H3-2/2015(H3N2)] were selected. Guinea pigs were divided into vaccinated and control groups. The vaccinated animals received either a multivalent antigenically heterologous or monovalent homologous vaccine, while the control animals remained unvaccinated. Following vaccination, all animals were intranasally challenged, and nasal wash samples were collected at different time points post-infection. The results showed that the homologous monovalent vaccine-induced hemagglutinin-specific antibodies against the Chilean pandemic H1N1pdm09 strain. However, the commercial heterologous multivalent vaccine failed to induce hemagglutinin-specific antibody titers against the H1N2 and H3N2 challenge strains. Furthermore, the homologous monovalent vaccine significantly reduced the duration of viral shedding and viral titers specifically against the Chilean pandemic H1N1pdm09 strain and heterologous multivalent vaccine only partial. These findings highlight the importance of regularly updating vaccine strains to match the circulating field strains for effective control of swine influenza. Further research is needed to develop vaccines that confer broader protection against diverse strains of swine influenza A virus.

Clinical characteristics of early-onset gastric cancer. A study in a Colombian population.

Gastric cancer is a multifactorial disease with important genetic and environmental factors. It is the fifth most common cancer in incidence, and the fourth cause of death secondary to cancer. The incidence of early-onset gastric cancer is increasing worldwide, but clinical information on these patients has not been well established. We analyzed the association between age and clinical, endoscopic, and histopathological characteristics of gastric cancer at the time of diagnosis in a Latin American population. A retrospective and descriptive cross-sectional study was carried out using the database of the Gastroenterology Service of the Clínica Foscal and Clínica Foscal Internacional in Bucaramanga, Colombia. Between January 2016 and December 2019, 259 de novo gastric cancer cases were diagnosed, of which 36 patients (13.9%) were 40 years old or younger. In patients with early-onset gastric, the prevalence of gastric cancer diagnosis was lower in men. A family history of gastric cancer or any other neoplasm was not associated with a higher prevalence of gastric neoplasms. In young patients, vomiting and ascites were more common, the preferred anatomical location was the body of the stomach, and the Borrmann IV classification and the diffuse-type histology were more likely. Our study showed an approximation of the characteristics of early-onset gastric cancer in a Latin American population, where we observed that early-onset gastric cancer has different demographic, anatomical, and histological features than late-onset gastric cancer.

Mass mortality event in South American sea lions (Otaria flavescens) correlated to highly pathogenic avian influenza (HPAI) H5N1 outbreak in Chile.

In Chile, since January 2023, a sudden and pronounced increase in strandings and mortality has been observed among South American (SA) sea lions (Otaria flavescens), prompting significant concern. Simultaneously, an outbreak of highly pathogenic avian influenza H5N1 (HPAIV H5N1) in avian species has emerged since December 2022. To investigate the cause of this unexpected mortality, we conducted a comprehensive epidemiological and pathologic study. One hundred sixty-nine SA sea lions were sampled to ascertain their HPAIV H5N1 status, and long-term stranding trends from 2009 to 2023 were analyzed. In addition, two animals were necropsied. Remarkably, a significant surge in SA sea lion strandings was observed initiating in January 2023 and peaking in June 2023, with a count of 4,545 stranded and deceased animals. Notably, this surge in mortality correlates geographically with HPAIV outbreaks affecting wild birds. Among 168 sampled SA sea lions, 34 (20%) tested positive for Influenza A virus, and 21 confirmed for HPAIV H5N1 2.3.4.4b clade in tracheal/rectal swab pools. Clinical and pathological evaluations of the two necropsied stranded sea lions revealed prevalent neurological and respiratory signs, including disorientation, tremors, ataxia, and paralysis, as well as acute dyspnea, tachypnea, profuse nasal secretion, and abdominal breathing. The lesions identified in necropsied animals aligned with observed clinical signs. Detection of the virus via immunohistochemistry (IHC) and real-time PCR in the brain and lungs affirmed the findings. The findings provide evidence between the mass mortality occurrences in SA sea lions and HPAIV, strongly indicating a causal relationship. Further studies are needed to better understand the pathogenesis and transmission.

Fusariosis in cancer patients: 13 case series report and literature review / Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hematooncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

Understanding the molecular profiling of diffuse gliomas classification: A brief overview.

Background: Gliomas represent almost 30% of all primary brain tumors and account for 80% of malignant primary ones. In the last two decades, significant progress has been made in understanding gliomas' molecular origin and development. These advancements have demonstrated a remarkable improvement in classification systems based on mutational markers, which contribute paramount information in addition to traditional histology-based classification. Methods: We performed a narrative review of the literature including each molecular marker described for adult diffuse gliomas used in the World Health Organization (WHO) central nervous system 5. Results: The 2021 WHO classification of diffuse gliomas encompasses many molecular aspects considered in the latest proposed hallmarks of cancer. The outcome of patients with diffuse gliomas relies on their molecular behavior and consequently, to determine clinical outcomes for these patients, molecular profiling should be mandatory. At least, the following molecular markers are necessary for the current most accurate classification of these tumors: (1) isocitrate dehydrogenase (IDH) IDH-1 mutation, (2) 1p/19q codeletion, (3) cyclin-dependent kinase inhibitor 2A/B deletion, (4) telomerase reverse transcriptase promoter mutation, (5) α-thalassemia/ mental retardation syndrome X-linked loss, (6) epidermal growth factor receptor amplification, and (7) tumor protein P53 mutation. These molecular markers have allowed the differentiation of multiple variations of the same disease, including the differentiation of distinct molecular Grade 4 gliomas. This could imply different clinical outcomes and possibly impact targeted therapies in the years to come. Conclusion: Physicians face different challenging scenarios according to the clinical features of patients with gliomas. In addition to the current advances in clinical decision-making, including radiological and surgical techniques, understanding the disease's molecular pathogenesis is paramount to improving the benefits of its clinical treatments. This review aims to describe straightforwardly the most remarkable aspects of the molecular pathogenesis of diffuse gliomas.

Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus in Wild Birds, Chile.

In December 2022, highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus emerged in Chile. We detected H5N1 virus in 93 samples and obtained 9 whole-genome sequences of strains from wild birds. Phylogenetic analysis suggests multiple viral introductions into South America. Continued surveillance is needed to assess risks to humans and domestic poultry.

Clinical characteristics of early-onset gastric cancer. A study in a Colombian population

Gastric cancer is a multifactorial disease with important genetic and environmental factors. It is the fifth most common cancer in incidence, and the fourth cause of death secondary to cancer. The incidence of early-onset gastric cancer is increasing worldwide, but clinical information on these patients has not been well established. We analyzed the association between age and clinical, endoscopic, and histopathological characteristics of gastric cancer at the time of diagnosis in a Latin American population. A retrospective and descriptive cross-sectional study was carried out using the database of the Gastroenterology Service of the Clínica Foscal and Clínica Foscal Internacional in Bucaramanga, Colombia. Between January 2016 and December 2019, 259 de novo gastric cancer cases were diagnosed, of which 36 patients (13.9%) were 40 years old or younger. In patients with early-onset gastric, the prevalence of gastric cancer diagnosis was lower in men. A family history of gastric cancer or any other neoplasm was not associated with a higher prevalence of gastric neoplasms. In young patients, vomiting and ascites were more common, the preferred anatomical location was the body of the stomach, and the Borrmann IV classification and the diffuse-type histology were more likely. Our study showed an approximation of the characteristics of early-onset gastric cancer in a Latin American population, where we observed that early-onset gastric cancer has different demographic, anatomical, and histological features than late-onset gastric cancer.

El cáncer gástrico es una enfermedad multifactorial con importantes factores genéticos y ambientales. Es el quinto cáncer más común en incidencia y la cuarta causa de muerte secundaria al cáncer. La incidencia del cáncer gástrico de inicio temprano está aumentando en todo el mundo, pero la información clínica sobre estos pacientes no está bien establecida. Analizamos la asociación entre la edad y las características clínicas, endoscópicas e histopatológicas del cáncer gástrico al momento del diagnóstico en una población latinoamericana. Se realizó un estudio retrospectivo y descriptivo de corte transversal utilizando la base de datos del Servicio de Gastroenterología de la Clínica Foscal y Clínica Foscal Internacional en Bucaramanga, Colombia. Entre enero de 2016 y diciembre de 2019 se diagnosticaron 259 casos de cáncer gástrico de novo, de los cuales 36 pacientes (13,9%) tenían 40 años o menos. En pacientes con enfermedad gástrica de inicio temprano, la prevalencia del diagnóstico de cáncer gástrico fue menor en los hombres. El antecedente familiar de cáncer gástrico o cualquier otra neoplasia no se asoció con una mayor prevalencia de neoplasias gástricas. En pacientes jóvenes fueron más frecuentes los vómitos y la ascitis, la localización anatómica preferida fue el cuerpo del estómago, siendo más probable la clasificación de Borrmann IV y la histología de tipo difuso. Nuestro estudio mostró una aproximación a las características del cáncer gástrico de inicio temprano en una población latinoamericana, donde observamos que el cáncer gástrico de inicio temprano tiene diferentes características demográficas, anatómicas e histológicas que el cáncer gástrico de inicio tardío.

Tracking the emergence of antigenic variants in influenza A virus epidemics in Brazil.

Influenza A virus (IAV) circulation patterns differ in North America and South America, with influenza seasons often characterized by different subtypes and strains. However, South America is relatively undersampled considering the size of its population. To address this gap, we sequenced the complete genomes of 220 IAVs collected between 2009 and 2016 from hospitalized patients in southern Brazil. New genetic drift variants were introduced into southern Brazil each season from a global gene pool, including four H3N2 clades (3c, 3c2, 3c3, and 3c2a) and five H1N1pdm clades (clades 6, 7, 6b, 6c, and 6b1). In 2016, H1N1pdm viruses belonging to a new 6b1 clade caused a severe influenza epidemic in southern Brazil that arrived early and spread rapidly, peaking mid-autumn. Inhibition assays showed that the A/California/07/2009(H1N1) vaccine strain did not protect well against 6b1 viruses. Phylogenetically, most 6b1 sequences that circulated in southern Brazil belong to a single transmission cluster that rapidly diffused across susceptible populations, leading to the highest levels of influenza hospitalization and mortality seen since the 2009 pandemic. Continuous genomic surveillance is needed to monitor rapidly evolving IAVs for vaccine strain selection and understand their epidemiological impact in understudied regions.

A postmortem study of patients vaccinated for SARS-CoV-2 in Colombia.

INTRODUCTION AND OBJECTIVE: A new coronavirus produces a disease designated as coronavirus disease 2019 (COVID-19). Vaccination against COVID-19 has resulted in decreased mortality. Postmortems of vaccinated patients play an important part in the forensic analysis of adverse effects after vaccination, which is essential for determining its efficacy and security. The main objective of this study was to describe the results of autopsies of patients vaccinated for SARS-CoV-2 carried out in two major centers in Colombia. MATERIALS AND METHODS: A descriptive cross-sectional study of 121 autopsies was performed following Colombian regulations in two main hospitals in Bogotá, Colombia, between March 1st and April 31st, 2021. RESULTS: 118 of the 121 patients (97.52%) had been vaccinated with CoronaVac (Sinovac); only 3 had received other vaccines. Sudden cardiac death was the leading cause of death, with pulmonary embolism another critical finding. No relation between the cause of death and vaccination against SARS-CoV-2 was found. CONCLUSIONS: A clinical autopsy is a vital for an accurate post-mortem diagnosis. Any relation between the SARS-CoV-2 vaccine and the cause of death should be carefully studied in order to provide the general public with evidence-based information about the safety of the vaccination.

Short-term complications and post-acute sequelae in hospitalized paediatric patients with COVID-19 and obesity: A multicenter cohort study.

BACKGROUND: Obesity increases the severity of coronavirus disease 2019 illness in adults. The role of obesity in short-term complications and post-acute sequelae in children is not well defined. OBJECTIVE: To evaluate the relationship between obesity and short-term complications and post-acute sequelae of SARS-CoV-2 infection in hospitalized paediatric patients. METHODS: An observational study was conducted in three tertiary hospitals, including paediatric hospitalized patients with a confirmatory SARS-CoV-2 RT-PCR from March 2020 to December 2021. Obesity was defined according to WHO 2006 (0-2 years) and CDC 2000 (2-20 years) growth references. Short-term outcomes were intensive care unit admission, ventilatory support, superinfections, acute kidney injury, and mortality. Neurological, respiratory, and cardiological symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms were considered as post-acute sequalae. Adjusted linear, logistic regression and generalized estimating equations models were performed. RESULTS: A total of 216 individuals were included, and 67 (31.02%) of them had obesity. Obesity was associated with intensive care unit admission (aOR = 5.63, CI95% 2.90-10.94), oxygen requirement (aOR = 2.77, CI95% 1.36-5.63), non-invasive ventilatory support (aOR = 6.81, CI95% 2.11-22.04), overall superinfections (aOR = 3.02 CI95% 1.45-6.31), and suspected bacterial pneumonia (aOR = 3.00 CI95% 1.44-6.23). For post-acute sequalae, obesity was associated with dyspnea (aOR = 9.91 CI95% 1.92-51.10) and muscle weakness (aOR = 20.04 CI95% 2.50-160.65). CONCLUSIONS: In paediatric hospitalized patients with COVID-19, severe short-term outcomes and post-acute sequelae are associated with obesity. Recognizing obesity as a key comorbidity is essential to develop targeted strategies for prevention of COVID-19 complications in children.

Metástasis tumor a tumor en pulmón: reporte de tres casos y revisión de la literatura / Tumor-to-tumor metastasis in the lung: report of three cases and review of the literature

Las metástasis tumor a tumor (MTT) corresponden a un evento poco frecuente en el cual se presenta metástasis de un tumor primario a otro tumor primario, bien sea benigno o maligno. El carcinoma de pulmón es un receptor poco habitual, pero uno de los donantes más frecuentes. En el presente articulo presentamos tres casos de MTT como órgano receptor el pulmón: el primero, de una mujer con antecedente de carcinoma papilar de tiroides y carcinoma ductal in situ de la mama, con presencia de MTT y carcinoma papilar de tiroides a un adenocarcinoma primario pulmonar. El segundo caso, es una mujer con MTT de carcinoma ductal de mama a un adenocarcinoma primario pulmonar. Y el tercero, de un MTT de un carcinoma ductal de mama a un hamartoma pulmonar. En los tres casos, fue fundamental la correlación clínico-patológica y los estudios complementarios de inmunohistoquímica.

Tumor-to-tumor metastases (TTM) correspond to a rare event in which a primary tumor metastasizes to another primary tumor, whether benign or malignant. Lung carcinoma is an unusual recipient, but one of the most frequent donors. In this article, we present three cases of TTM to the lung: the first one is of a woman with a history of papillary thyroid carcinoma and ductal carcinoma in situ of the breast, with the presence of TTM and papillary thyroid carcinoma to a primary adenocarcinoma of the lung. The second case is of a woman with TTM from ductal carcinoma of the breast to a primary pulmonary adenocarcinoma, and the third is TTM from a breast ductal carcinoma to a pulmonary hamartoma. In all three cases, the clinical-pathological connection and complementary immunohistochemical studies were essential

Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura / Fusariosis in cancer patients: 13 case series report and literature review

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hemato-oncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.