Zika Virus: A Neurotropic Warrior against High-Grade Gliomas-Unveiling Its Potential for Oncolytic Virotherapy.

Gliomas account for approximately 75-80% of all malignant primary tumors in the central nervous system (CNS), with glioblastoma multiforme (GBM) considered the deadliest. Despite aggressive treatment involving a combination of chemotherapy, radiotherapy, and surgical intervention, patients with GBM have limited survival rates of 2 to 5 years, accompanied by a significant decline in their quality of life. In recent years, novel management strategies have emerged, such as immunotherapy, which includes the development of vaccines or T cells with chimeric antigen receptors, and oncolytic virotherapy (OVT), wherein wild type (WT) or genetically modified viruses are utilized to selectively lyse tumor cells. In vitro and in vivo studies have shown that the Zika virus (ZIKV) can infect glioma cells and induce a robust oncolytic activity. Consequently, interest in exploring this virus as a potential oncolytic virus (OV) for high-grade gliomas has surged. Given that ZIKV actively circulates in Colombia, evaluating its neurotropic and oncolytic capabilities holds considerable national and international importance, as it may emerge as an alternative for treating highly complex gliomas. Therefore, this literature review outlines the generalities of GBM, the factors determining ZIKV's specific tropism for nervous tissue, and its oncolytic capacity. Additionally, we briefly present the progress in preclinical studies supporting the use of ZIKV as an OVT for gliomas.

Detection of variable genotypes in common human papillomavirus-associated invasive penile squamous cell carcinomas: a study of 177 human papillomavirus-positive cases.

Human papillomavirus (HPV) is detected in 30-50% of invasive penile carcinomas, and it is frequently associated with basaloid and warty morphological features. Based on this heterogeneity and different clinical behaviors, we hypothesized a variation in their HPV genotypic composition. To test this, we evaluated 177 HPV-positive cases: basaloid (114), warty-basaloid (28), and warty (condylomatous) (35) invasive carcinomas. HPV DNA detection and genotyping was performed using the SPF-10/DEIA/LiPA25 system. Nineteen HPV genotypes were detected. High-risk HPVs predominated (96%), and low-risk HPVs were rarely present. Most common genotype was HPV16 followed by HPVs 33 and 35. According to the genotypes identified, 93% of the cases would be covered with current vaccination programs. There was a significant variation in the distribution of HPV16 and non-HPV16 genotypes according to histological subtype. HPV16 was significantly frequent in basaloid (87%) and was less frequent in warty carcinomas (61%). This molecular difference, along with their distinctive macro-microscopic and prognostic features, makes basaloid and warty carcinomas unique. The gradual decreasing frequency of HPV16 demonstrated in basaloid, warty-basaloid, and warty carcinomas suggest that the basaloid cell, present in those types in decreasing proportions, may be responsible for the differences.

Incidence and Mortality Rates for Childhood Acute Lymphoblastic Leukemia in Puerto Rican Hispanics, 2012-2016.

BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for 80% of all leukemias diagnosed in children. Although ALL age patterns are consistent across racial/ethnic groups, their incidence and mortality rates are highly variable. We assessed the age-standardized ALL incidence and mortality rates of Puerto Rican Hispanic (PRH) children and compared them with those of US mainland Hispanics (USH), non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Non-Hispanic Asian or Pacific Islanders (NHAPI). METHODS: Differences between racial/ethnic groups were assessed by estimating the standardized rate ratio (SRR) for 2010 to 2014. Secondary data analyses of the Puerto Rico Central Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases were performed for the 2001 to 2016 period. RESULTS: PRH children had 31% lower incidence rates than USH, but 86% higher incidence rates than NHB. In addition, the incidence trends of ALL increased significantly from 2001 to 2016 among PRH and USH, with 5% and 0.9% per year, respectively. Moreover, PRH have a lower 5-year overall survival (81.7%) when compared with other racial/ethnic groups. CONCLUSIONS: PRH children were found to have disparities in ALL incidence and mortality rates compared with other racial/ethnic groups in the US. Additional research is warranted to identify the genetic and environmental risk factors that may be associated with the disparities observed. IMPACT: This is the first study reporting the incidence and mortality rates of childhood ALL for PRH and making comparisons with other racial/ethnic groups in the US. See related commentary by Mejía-Aranguré and Núñez-Enríquez, p. 999.

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico.

BACKGROUND: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.

Molecular profiling of colorectal cancer in a genetically admixed Hispanic population.

BACKGORUND: Colorectal cancer (CRC) is among the leading causes of cancer-related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients. METHODS: We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next-generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan-Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)-Non-Hispanic, and GENIE-Hispanic datasets. RESULTS: Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE-Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability-high (MSI), wild-type KRAS, wild-type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients. CONCLUSION: This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non-Hispanic and USH populations.

The dual pathogenesis of penile neoplasia: The heterogeneous morphology of human papillomavirus-related tumors.

Objective: Penile neoplasia, usually of squamous histogenesis, is currently classified into human papillomavirus (HPV)-related or -dependent and non-HPV-related or -independent. There are distinct morphological differences among the two groups. New research studies on penile cancer from Northern countries showed that the presence of HPV is correlated with a better prognosis than virus negative people, while studies in Southern countries had not confirmed, perhaps due to differences in staging or treatment. Methods: We focused on the description of the HPV-related carcinomas of the penis. The approach was to describe common clinical features followed by the pathological features of each entity or subtype stressing the characteristics for differential diagnosis, HPV genotypes, and prognostic features of the invasive carcinomas. Similar structure was followed for penile intraepithelial neoplasia, except for prognosis because of the scant evidence available. Results: Most of HPV-related lesions can be straightforwardly recognized by routine hematoxylin and eosin stains, but in some cases surrogate p16 immunohistochemical staining or molecular methods such as in situ hybridization or polymerase chain reaction can be utilized. Currently, there are eight tumor invasive variants associated with HPV, as follows: basaloid, warty, warty-basaloid, papillary basaloid, clear cell, medullary, lymphoepithelioma-like, and giant condylomas with malignant transformation. Conclusion: This review presents and describes the heterogeneous clinical, morphological, and genotypic features of the HPV-related subtypes of invasive and non-invasive penile neoplasia.

Riesgo de recurrencia y factores de riesgo de invasión del cáncer diferenciado de tiroides / Risk of recurrence and risk factors for invasion of differentiated thyroid cancer

Introducción: El cáncer diferenciado de tiroides (CDT) se encuentra representado por el carcinoma papilar y el carcinoma folicular. Comprende la gran mayoría (>90%) de todos los cánceres de tiroides. Objetivos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Materiales y métodos: Estratificar el riesgo de recurrencia inicial de los pacientes con CDT. Relacionar la edad, sexo y tamaño tumoral con el riesgo de recurrencia, invasión capsular, ganglionar, vascular y de tejido peritiroideo. Resultados: El 87% fueron del sexo femenino. La edad media fue de 43±14 años. Predominó el riesgo de recurrencia bajo en el 49% de los pacientes, seguido del riesgo intermedio (33%) y riesgo alto (18%). El tamaño tumoral ˃1cm confiere mayor riesgo de ser estratificado como riesgo de recurrencia intermedio/alto (OR 5,7 IC 95% 3,6-9). El sexo masculino representó mayor riesgo de invasión ganglionar (OR 2,8 IC 95% 1,2-6,6); la edad ≥55 años lo fue en la invasión vascular (OR 2,1 IC 95% 1,1-4,1); el tamaño >1cm constituyó un mayor riesgo de manera significativa de invasión capsular (OR 10,5 IC 95% 6,5-17), invasión ganglionar (OR 10,2 IC 95% 3,8-26,9), invasión vascular (OR 30,7 IC 95% 4,2-224) e invasión de tejido peritiroideo (OR 5,2 IC 95% 3,3-8,2). Conclusión: El riesgo de recurrencia inicial más frecuente fue el riesgo bajo. El sexo masculino, la edad ≥55años y el tamaño >1cm constituyen factores de riesgo de invasión a estructuras vecinas.

Introduction: Differentiated thyroid cancer (DTC) is represented by papillary carcinoma and follicular carcinoma. It comprises the vast majority (> 90%) of all thyroid cancers. Objectives: Stratify the risk of initial recurrence of patients with DTC. Relate age, sex, and tumor size to the risk of recurrence, capsular, nodal, vascular, and perithyroid tissue invasion. Materials and methods: Observational, descriptive, retrospective, cross-sectional study with an analytical component. A total of 432 patients with a diagnosis of DTC from Hospital de Clínicas, Instituto de Previsión Social and Instituto Nacional del Cáncer between 2011 and 2015 were included. Results: 87% were female. The mean age was 43 ± 14 years. Low recurrence risk predominated in 49% of patients, followed by intermediate risk (33%) and high risk (18%). Male sex, age ≥55 years and tumor size ˃1cm confer a higher risk of being stratified as intermediate / high recurrence risk, but only size> 1cm was significantly (OR 5.7 95% CI 3.6-9). Male sex represented a higher risk of lymph node invasion (OR 3.1 95% CI 1.4-2.8) and vascular invasion (OR 2.3 95% CI 1.1-4.8); age ≥55 years was in the vascular invasion (OR 2.6 95% CI 1.4-4.9); size> 1cm constituted a significantly higher risk of capsular invasion (OR 10.7 95% CI 6.7-17.3), nodal invasion (OR 10.5 95% CI 4-27.7), vascular invasion (OR 33 95% CI 4.5-244) and invasion of perithyroid tissue (OR 5.1 95% CI 3.2-8.1). Conclusion: The most frequent initial recurrence risk was low risk. Male sex, age ≥55 years, and size> 1cm are risk factors for invasion of neighboring structures.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. CONCLUSIONS: Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science Framework (https://osf.io/9ewys/).

Natural Products as Outstanding Alternatives in Diabetes Mellitus: A Patent Review.

Diabetes mellitus (DM) is a metabolic syndrome that can be considered a growing health problem in the world. High blood glucose levels are one of the most notable clinical signs. Currently, new therapeutic alternatives have been tackled from clinicians' and scientists' points of view. Natural products are considered a promising source, due to the huge diversity of metabolites with pharmaceutical applications. Therefore, this review aimed to uncover the latest advances in this field as a potential alternative to the current therapeutic strategies for the treatment of DM. This purpose is achieved after a patent review, using the Espacenet database of the European Patent Office (EPO) (2016-2022). Final screening allowed us to investigate 19 patents, their components, and several technology strategies in DM. Plants, seaweeds, fungi, and minerals were used as raw materials in the patents. Additionally, metabolites such as tannins, organic acids, polyphenols, terpenes, and flavonoids were found to be related to the potential activity in DM. Moreover, the cellular transportation of active ingredients and solid forms with special drug delivery profiles is also considered a pharmaceutical technology strategy that can improve their safety and efficacy. From this perspective, natural products can be a promissory source to obtain new drugs for DM therapy.

Detección de mutaciones del Gen KRAS en pacientes paraguayos con cáncer colorrectal / Detection of KRAS Gene mutations in paraguayan patients with colorectal cancer

El estado mutacional del KRAS ha sido considerado como biomarcador para tratamientos biológicos tras varios ensayos clínicos realizados en pacientes con cáncer colorrectal metastásico. Reportes recientes indican que las frecuencias de mutación del gen KRAS en pacientes con CCR de Asia, Europa y Latinoamérica están entre el 24%, 36% y 40%, respectivamente. Paraguay no cuenta con este tipo de informes, a pesar de registrar anualmente en promedio 75 nuevos casos de pacientes diagnosticados con CCR sólo en el Servicio de Cirugía General del Hospital Central del Instituto de Previsión Social (IPS). El presente trabajo ha implementado este análisis de rutina, prerrequisito obligatorio para la administración de fármacos basados en anticuerpos terapéuticos, y revelado una frecuencia de mutación del gen KRAS del 34% en pacientes paraguayos con CCR que acuden a los Servicios del Hospital Central del IPS

The mutational status of the KRAS has been consider as a biomarker for biological treatments after several clinical trials carried out in patient with metastatic colorectal cancer. Recent reports indicate that the KRAS gene mutation frequencies in CRC patients from Asia, Europe, and Latin America are between 24%, 36%, and 40%, respectively. Paraguay does not have this kind of reports, despite registering an average of 75 new cases of patients diagnosed with CRC per year only in the General Surgery Service of the "Central Hospital - Instituto de Prevision Social (IPS)". The present work has implemented this routine analysis, a mandatory prerequisite for the administration of drugs based on therapeutic antibodies and revealed a KRAS gene mutation frequency of 34% in Paraguayan patients with CRC who attend the IPS Central Hospital Services

Strengthening Pathology Capacity to Deliver Quality Cancer Care in Cities in LMICs.

Diagnostic pathology services for oncology health systems are essential; yet, surveys, observations, and hard data from across low- and middle-income countries have revealed that these services are almost always lacking adequate quality and often missing completely. The City Cancer Challenge Foundation (C/Can), the American Society for Clinical Pathology, and C/Can partner cities undertook intense analysis of their existing pathology services as part of a year-long assessment process including the specific formation of a pathology-focused team. Internal and external expert assessments identified sustainable solutions adapted to the local context and level of resources and created specific local implementation projects. Through local leadership, capacity development, and collaboration, services were improved city-wide in three cities: Cali, Colombia; Asunción, Paraguay; and Yangon, Myanmar. Common problems identified across cities included deficiencies in personnel training, equipment, reagents, processes, quality, and coordination. Specific solutions included quality training, standard process development and regulation, implementation of new services, and public-private collaboration. As the first cities joining the C/Can initiative, Cali, Asunción, and Yangon demonstrate the success of the approach and the value of local expertise in identifying problems and solutions. The additional value of international partners' expertise created opportunities for growth through mentorship and technical support. Importantly, the power of healthcare programs with strong political support is emphasized.

Recognition of musical emotions in the behavioral variant of frontotemporal dementia / Reconocimiento de emociones musicales en la variante conductual de la demencia frontotemporal

ABSTRACT Introduction: Multiple investigations have revealed that patients with behavioral variant of frontotemporal dementia (bvFTD) experience difficulty recognizing emotional signals in multiple processing modalities (e.g., faces, prosody). Few studies have evaluated the recognition of musical emotions in these patients. This research aims to evaluate the ability of subjects with bvFTD to recognize musical stimuli with positive and negative emotions, in comparison with healthy subjects. Methods: bvFTD (n = 12) and healthy control participants (n = 24) underwent a test of musical emotion recognition: 56 fragments of piano music were randomly reproduced, 14 for each of the emotions (happiness, sadness, fear, and peacefulness). Results: In the subjects with bvFTD, a mean of correct answers of 23.6 (42.26%) was observed in contrast to the control subjects, where the average number of correct answers was 36.3 (64.8%). Statistically significant differences were found for each of the evaluated musical emotions and in the total score on the performed test (P<.01). The within-group analysis showed greater difficulty for both groups in recognizing negative musical emotions (sadness, fear), with the subjects with bvFTD exhibiting worse performance. Conclusions: Our results indicate that the recognition of musical stimuli with positive (happiness, peacefulness) and negative (sadness, fear) emotions are compromised in patients with bvFTD. The processing of negative musical emotions is the most difficult for these individuals.

RESUMEN Introducción: Múltiples estudios han revelado que los sujetos con la variante conductual de la demencia frontotemporal (bvFTD) tienen dificultades para reconocer señales emocionales en múltiples diferentes modalidades de procesamiento (p. ej., rostros, prosodia). Actualmente, existen pocos estudios que evalúen el reconocimiento de emociones musicales en esta población. El objetivo de esta investigación es evaluar la capacidad de los sujetos con bvFTD para reconocer estímulos musicales con emociones positivas y negativas, en comparación con sujetos sanos. Métodos: Se evaluó a 12 pacientes con bvFTD y 24 controles sanos mediante una prueba de reconocimiento de emociones musicales. Se reprodujeron aleatoriamente 56 fragmentos de música de piano, 14 para cada una de las emociones (felicidad, tristeza, miedo y tranquilidad). Resultados: En los pacientes con bvFTD, se observó una media de respuestas correctas de 23,6 (42,26%), en contraste con los sujetos de control, quienes obtuvieron un promedio de respuestas correctas de 36,3 (64,8%). Se encontraron diferencias estadísticamente significativas para cada una de las emociones musicales evaluadas y en la puntuación total de la prueba (p < 0,01). El análisis intragrupal mostró una mayor dificultad en ambos grupos para el reconocimiento de emociones musicales negativas (tristeza, miedo), y los sujetos con bvFTD son los que mostraron peor desempeño. Conclusiones: Nuestros resultados indican que el reconocimiento de estímulos musicales con emociones positivas (felicidad, tranquilidad) y negativas (tristeza, miedo) se ve afectado en pacientes con bvFTD. Las emociones musicales negativas son las más difíciles de reconocer para estos pacientes.

What Is New in the Pathologic Staging of Penile Carcinoma in the 8th Edition of AJCC TNM Model: Rationale for Changes With Practical Stage-by-stage Category Diagnostic Considerations.

For >50 years the tumor, node, metastasis (TNM) classification model of malignant tumors has been the main resource for clinicians, pathologists, radiologists and public health professionals ensuring a homogeneous classification and patients' management based on common staging and prognosis factors. Penile cancer was first included for staging in the third edition of the TNM classification with several changes in the last version, the 8th edition of the AJCC TNM Manual, in 2017. Some changes in the pT category were done due to recent knowledge regarding the prognostic importance of anatomical level of invasion, vascular and perineural invasion and tumor grading. These changes must be interpreted in the light of a required understanding of the complex anatomy of penile compartments especially their histological boundaries, the morphological differences of each level needed for the correct classification, the heterogeneity of penile squamous cell carcinomas and an adequate criticism of the current model used by the TNM system. We present here a series of stage-by-stage category diagnostic considerations based on the clinical experience acummulated over the years of applying the different TNM staging classifications in our large clinical practice. Some discrepancies will need well-designed prospective studies for im4proving the actual classification.

Prevalencia de Cáncer de Tiroides en Centros de Referencia del Paraguay / Prevalence of Thyroid Cancer in Reference Centers of Paraguay

Introducción: El Cáncer de tiroides es la neoplasia maligna más frecuente del sistema endócrino. Durante las últimas décadas se ha observado un aumento de su incidencia de forma progresiva en numerosos países y regiones del mundo. Objetivos: Determinar la prevalencia de Cáncer de tiroides y, los tipos histológicos, en 3 hospitales de referencia en Paraguay. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo, de corte transversal. Se incluyó a todos los pacientes sometidos a tiroidectomía parcial o total en el Hospital de Clínicas, Instituto de Previsión Social e Instituto Nacional del Cáncer, entre los años 2011 y 2015. Resultados: La prevalencia de cáncer de tiroides fue de 23,7% de 1913 pacientes sometidos a tiroidectomía. El 85,7% fueron del sexo femenino. La edad media fue de 43±14 años. El 85,4 % de los pacientes presentó Carcinoma Papilar; el 9,5% Carcinoma Folicular; el 3,1% Carcinoma Medular; el 1,6% Carcinoma Anaplásico y el 0,4% Carcinoma Papilar + Carcinoma Folicular en el mismo paciente. El sexo femenino fue más frecuente en todos los tipos histológicos y, el Carcinoma Medular resultó igual en ambos sexos. La edad media de los pacientes con Carcinoma Papilar fue de 42±13 años, Carcinoma Medular 49±15 años, del Carcinoma Folicular 50±18 años y Carcinoma Anaplásico 69±11 años. El tamaño promedio del Carcinoma Papilar fue de 19±17 mm, del Carcinoma Folicular 53±24 mm, del Carcinoma Medular 40±22 mm, y el Carcinoma Anaplásico 50±35 mm. Conclusión: Aproximadamente 1 de cada 4 pacientes sometidos a tiroidectomía presentó cáncer de tiroides, siendo más frecuente en el sexo femenino y, el Carcinoma Papilar es el tipo histológico más frecuente.

Introduction: Thyroid cancer is the most frequent malignant neoplasm of the endocrine system. During the last decades, an increase in its incidence has been observed progressively in many countries and regions of the world. Objectives: To determine the prevalence of thyroid cancer and its histological types in thyroidectomies carried out in reference hospitals in Paraguay. Materials and methods: Observational, descriptive, retrospective, cross-sectional study. All patients undergoing partial or total thyroidectomy at the Hospital de Clínicas, Instituto de Previsión Social and Instituto Nacional del Cáncer between 2011 and 2015 were included. Results: The prevalence of thyroid cancer was 23.7% of 1913 patients undergoing thyroidectomy. 85.7% were female. The mean age was 43 ± 14 years. 85.4% of the patients presented Papillary Carcinoma; 9.5% Follicular Carcinoma; 3.1% Medullary Carcinoma; 1.6% Anaplastic Carcinoma and 0.4% Papillary Carcinoma + Follicular Carcinoma in the same patient. The mean age of the patients with Papillary Carcinoma was 42 ± 13 years, Medullary Carcinoma 49 ± 15 years, Follicular Carcinoma 50 ± 18 years, and Anaplastic Carcinoma 69 ± 11 years. The average size of Papillary Carcinoma was 19 ± 17 mm, Medullary Carcinoma 40 ± 22 mm, Anaplastic Carcinoma 50 ± 35 mm, and Follicular Carcinoma 53 ± 24 mm. Conclusion: About 1 in 4 patients undergoing thyroidectomy has thyroid cancer, it is more frequent in women, and the most frequent histological type is Papillary Carcinoma.

[Diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders: A systematic review protocol]. / Precisión diagnóstica de biomarcadores salivales para cáncer oral y desórdenes potencialmente malignos: protocolo de revisión sistemática.

INTRODUCTION: Oral cancer has a 5-year survival rate of 50% because diagnosis is commonly performed at an advanced stage of the disease, so new diagnostic tools are needed. Nowadays, there is a vast number of publications suggesting the use of salivary biomarkers for oral cancer and potentially malignant disorders diagnosis, but their diagnostic accuracy is unclear. Thus, the goal of this systematic review is to evaluate the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. METHODS: This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will include primary studies assessing the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. Studies must report data about sensitivity and specificity; gold standard must be the histopathology diagnosis. We will search MEDLINE, EMBASE, the Cochrane Library, and gray literature. Two authors will independently select the studies and extract the data. The methodology quality of studies will be determined using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). EXPECTED RESULTS AND CONCLUSION: Our findings will provide information about the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders.

INTRODUCCIÓN: El cáncer oral tiene una tasa de supervivencia a los cinco años de 50%, debido a que frecuentemente su diagnóstico es realizado en estadios avanzados. Por lo tanto, son necesarias nuevas ayudas diagnósticas. Actualmente, existe un número significativo de publicaciones científicas sugiriendo el uso de biomarcadores salivales para el diagnóstico de cáncer oral. Sin embargo, son desconocidas las propiedades diagnósticas de estos biomarcadores. El objetivo de esta revisión sistemática es evaluar la evidencia sobre la precisión diagnóstica de biomarcadores salivales usados en la identificación de cáncer oral y desórdenes potencialmente malignos. MÉTODOS: Este protocolo es reportado en concordancia con el Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Se incluirán estudios evaluando la precisión diagnóstica de biomarcadores salivales para cáncer oral y desórdenes potencialmente malignos. Estos deberán reportar sensibilidad y especificidad, y utilizar como estándar de referencia un diagnóstico histopatológico. Se realizará una búsqueda en MEDLINE, EMBASE, Cochrane Library y literatura gris. Dos autores independientemente seleccionarán los estudios y extraerán los datos. La calidad metodológica de los estudios será determinada usando The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULTADOS ESPERADOS Y CONCLUSIÓN: Los hallazgos de esta revisión sistemática proporcionarán información acerca de la precisión diagnóstica de los biomarcadores salivales para diagnóstico de cáncer oral y desórdenes potencialmente malignos.

Currículos de salud sexual y reproductiva en programas de educación superior para América Latina / Sexual and reproductive health curricula in higher education programs for Latin America / Grades curriculares de saúde sexual e reprodutiva nos programas de ensino superior para a América Latina

Objetivo: identificar la inclusión de la propuesta temática curricular de la Federación Latinoamericana de Obstetricia y Ginecología (FLASOG) sobre salud sexual y reproductiva en programas de pregrado (Medicina) y posgrado (Obstetricia y Ginecología) en un grupo de universidades e instituciones de educación superior de Latinoamérica y el Caribe. Método: estudio descriptivo de corte transversal en el cual se aplicó una encuesta a universidades de Latinoamérica y El Caribe durante el año 2017 para determinar si los contenidos de los programas con relación a salud sexual y reproductiva corresponden a la propuesta temática de la FLASOG, tanto en pregrado (Medicina) como en posgrado (Obstetricia y Ginecología). Resultados: todos los programas de pregrado evaluados incluyen dentro del currículo los siguientes temas: m étodos anticonceptivos, aborto y morbimortalidad materna y el 36,4 % contemplan salud sexual en la tercera edad. Todos los programas de posgrado evaluados estudian métodos anticonceptivos, anticoncepci ón en posparto y posaborto, morbimortalidad materna, aborto, y maternidad saludable. Solo el 55,6 % de ellos tienen temáticas relacionadas con interrupción voluntaria del embarazo y salud sexual en la tercera edad. Conclusiones: los programas evaluados cuentan con docentes dedicados a educación en salud sexual y reproductiva en sus programas, aunque en la mayoría de las instituciones (76,9 % ) no existe un proceso formal de evaluación y retroalimentación. Todas las universidades que respondieron la encuesta trabajan tres temas en sus contenidos curriculares de pregrado: aborto, anticoncepción y morbimortalidad materna, t ópicos que han sido considerados de alto impacto en la salud sexual y reproductiva de las mujeres. La interrupción voluntaria del embarazo se discute en dos de cada tres universidades que respondieron la encuesta. El tema de salud sexual en la tercera edad no se incluye en los programas.

Objective: to identify if Latin American and Caribbean higher education institutions include in their curriculum the sexual and reproductive health topics proposed by the Latin American Federation of Obstetrics and Gynecology (FLASOG for its acronym in Spanish) in undergraduate and graduate programs. Methods: descriptive, cross sectional study developed in the year 2017. A survey was sent to universities in Latin America and the Caribbean to evaluate if the sexual and reproductive health contents in the curriculum of undergraduate (medicine) and graduate schools (obstetrics and gynecology) correspond to the ones proposed by FLASOG. Results: 100 % of assessed undergraduate programs include the following topics in their curriculum: birth control methods, abortion, maternal morbidity and mortality, and 36.4 % include sexual health in the elderly. 100 % of graduate programs evaluated include: birth control methods, maternal morbidity and mortality, abortion, and healthy maternity, and 55.6 % include legal pregnancy termination and sexual health in the elderly. Conclusions: All the higher education programs evaluated have faculty for sexual and reproductive health, but most institutions (76 .9 % ) do not have a formal process for evaluation and feedback. All the universities include in their undergraduate programs the following topics: abortion, birth control methods and maternal morbidity and mortality, all of which have been considered of high impact in sexual and reproductive health of women. However, topics such as legal termination of pregnancy are only included in two out of three universities evaluated, and sexual health in the elderly is rarely included in the curriculum.

Objetivo: identificar a inclusão da proposta temática da Federação Latino-Americana de Obstetrícia e Ginecologia (FLASOG) em saúde sexual e reprodutiva nos programas de graduação (Medicina) e pós-graduação (Obstetrícia e Ginecologia) em um grupo de universidades e instituições de ensino superior da América Latina e do Caribe. Método: estudo descritivo transversal. Foi aplicado um questionário em programas de cursos de graduação e pós-graduação de universidades da América Latina e do Caribe em 2017, para determinar se o conteúdo dos programas relacionados à saúde sexual e reprodutiva correspondem à proposta temática da FLASOG no nível de graduação (Medicina) e de pós-graduação (Obstetrícia e Ginecologia). Resultados: todos os programas de graduação avaliados incluíram os seguintes tópicos no currículo: métodos contraceptivos, aborto e morbimortalidade materna; ainda, 36,4% dos programas abrangem temas relacionados à saúde sexual nos idosos. Todos os programas de pós-graduação avaliados estudam métodos contraceptivos, contracepção no pós-parto e pós-aborto, morbimortalidade materna, aborto e maternidade saudável. Apenas 55,6% desses programas têm tópicos relacionados à interrupção voluntária da gravidez e sobre a saúde sexual em idosos. Conclusões: os programas avaliados têm professores enfocados na educação da saúde sexual e reprodutiva, embora na maioria das instituições (76,9%) não exista um processo formal de avaliação e feedback. Todas as universidades que responderam à pesquisa trabalham com três tópicos em seu conteúdo curricular de graduação: aborto, contracepção e morbimortalidade materna, considerados de alto impacto na saúde sexual e reprodutiva das mulheres. A interrupção voluntária da gravidez é discutida em uma proporção de duas em cada três universidades que responderam ao questionário. A saúde sexual em idosos não está incluída nos programas

Sarcoma de Células Claras en pierna de mujer de 28 años / Clear cell sarcoma on 28 years old woman leg

Los tumores de partes blandas son tumores que se presentan en adultos, aproximadamente a los 60 años. De estos tumores los sarcomas son poco frecuentes y tienen preferencia en las extremidades y muchas veces invaden estructuras músculo aponeuróticas cercanas, y poca invasión vascular o nerviosa lo que las hace de fácil acceso con poca morbilidad para su biopsia. El diagnóstico de los tumores de partes blandas se basa en el estudio histológico de anatomía patológica y, a veces se debe asociar a estudios de citogenética para poder tener un diagnóstico específico. El tratamiento principal es quirúrgico y puede llegar estar asociado a terapia adyuvante.

Soft tissue tumors are tumors that occur in adult's age, at about 60 age. Of these tumors, sarcomas are rare and have preference in the extremities, and often invade nearby muscle-fascia structures, and little vascular or nerve invasion, making them easily accessible with little morbidity for biopsy. The diagnosis of soft tissue tumors is based on the histological study of pathological anatomy and, sometimes, it must be associated with cytogenetic studies in order to have specific diagnosis. The main treatment is surgical and may end up being associated with adjuvant therapy.

Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews.

BACKGROUND: Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps. METHODS: We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios. RESULTS: A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores. CONCLUSIONS: Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

Topographical Evaluation of Penile Lichen Sclerosus Reveals a Lymphocytic Depleted Variant, Preferentially Associated With Neoplasia: A Report of 200 Cases.

Since the seminal study of Hart and Helwig in 1975, there are few detailed pathological studies of lichen sclerosus (LS). The aims of this study were to provide a detailed histopathological description of penile LS, as well as to explore its relationship with penile intraepithelial neoplasia (PeIN) or invasive carcinoma. We evaluated 200 patients and designed a topographical approach for the histological evaluation focusing in alterations of the following anatomical layers: squamous epithelium, lamina propria, dartos, and corpus spongiosum. We documented the quantity and topographical location of stromal lymphocytes. The prevalent lesions found were epithelial hyperplasia, atrophy, PeIN, basal cell vacuolization, lamina propria sclerosis, and variable patterns of lymphocytic infiltration. Various unique patterns of stromal sclerosis were described: perivascular, globular, linear, and solid fibrosis/hyalinization; any of them were found to be diagnostic for LS. The variation in the topography and density of lymphocytes was determinant for the identification of LS morphological variants: lichenoid, band-like, lymphocytic depleted, and mixed. A major finding was the identification of the variant designated as lymphocytic depleted LS, which we considered as the morphological prototype of LS associated with penile neoplasia. The detailed description of this complex lesion presented in this study may help pathologists in practice to identify and better define LS. The identification of the special variants suggests a role of the stromal lymphocytes in the process of carcinogenesis. Confirmation of the observations with more studies is necessary to determine the significance of these findings.

Precisión diagnóstica de biomarcadores salivales para cáncer oral y desórdenes potencialmente malignos: protocolo de revisión sistemática / Diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders: a systematic review protocol

INTRODUCCIÓN: El cáncer oral tiene una tasa de supervivencia a los cinco años de 50%, debido a que frecuentemente su diagnóstico es realizado en estadios avanzados. Por lo tanto, son necesarias nuevas ayudas diagnósticas. Actualmente, existe un número significativo de publicaciones científicas sugiriendo el uso de biomarcadores salivales para el diagnóstico de cáncer oral. Sin embargo, son desconocidas las propiedades diagnósticas de estos biomarcadores. El objetivo de esta revisión sistemática es evaluar la evidencia sobre la precisión diagnóstica de biomarcadores salivales usados en la identificación de cáncer oral y desórdenes potencialmente malignos. MÉTODOS: Este protocolo es reportado en concordancia con el Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Se incluirán estudios evaluando la precisión diagnóstica de biomarcadores salivales para cáncer oral y desórdenes potencialmente malignos. Estos deberán reportar sensibilidad y especificidad, y utilizar como estándar de referencia un diagnóstico histopatológico. Se realizará una búsqueda en MEDLINE, EMBASE, Cochrane Library y literatura gris. Dos autores independientemente seleccionarán los estudios y extraerán los datos. La calidad metodológica de los estudios será determinada usando The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULTADOS ESPERADOS Y CONCLUSIÓN: Los hallazgos de esta revisión sistemática proporcionarán información acerca de la precisión diagnóstica de los biomarcadores salivales para diagnóstico de cáncer oral y desórdenes potencialmente malignos.

INTRODUCTION: Oral cancer has a 5-year survival rate of 50% because diagnosis is commonly performed at an advanced stage of the disease, so new diagnostic tools are needed. Nowadays, there is a vast number of publications suggesting the use of salivary biomarkers for oral cancer and potentially malignant disorders diagnosis, but their diagnostic accuracy is unclear. Thus, the goal of this systematic review is to evaluate the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. METHODS: This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will include primary studies assessing the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. Studies must report data about sensitivity and specificity; gold standard must be the histopathology diagnosis. We will search MEDLINE, EMBASE, the Cochrane Library, and gray literature. Two authors will independently select the studies and extract the data. The methodology quality of studies will be determined using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). EXPECTED RESULTS AND CONCLUSION: Our findings will provide information about the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders.