Germline pathogenic variants associated with triple-negative breast cancer in US Hispanic and Guatemalan women using hospital and community-based recruitment strategies.

PURPOSE: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. METHODS: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala. RESULTS: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001). CONCLUSION: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.

Extrachromosomal Amplification of Human Papillomavirus Episomes Is a Mechanism of Cervical Carcinogenesis.

SIGNIFICANCE: Multimers of the HPV genome are generated in cervical tumors replicating as extrachromosomal episomes, which is associated with deletion and rearrangement of the HPV genome and provides a mechanism for oncogenesis without integration.

Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer.

PURPOSE: Mutations in hereditary breast cancer genes play an important role in the risk for cancer. METHODS: Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. RESULTS: A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). CONCLUSIONS: Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

A review of the main histopathological findings in coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has been declared by the World Health Organization as an emerging public health problem of global importance and classified as a pandemic. SARS-CoV-2 infection can result in diverse, multiorgan pathology, the most significant being in the lungs (diffuse alveolar damage in its different phases, microthrombi, bronchopneumonia, necrotizing bronchiolitis, viral pneumonia), heart (lymphocytic myocarditis), kidney (acute tubular injury), central nervous system (microthrombi, ischemic necrosis, acute hemorrhagic infarction, congestion, and vascular edema), lymph nodes (hemophagocytosis and histiocytosis), bone marrow (hemophagocytosis), and vasculature (deep vein thrombosis). An understanding of the spectrum and frequency of histologic findings in COVID-19 is essential for gaining a better understanding of disease pathophysiology and its ongoing impact on public health. To this end, we conducted a systematic meta-analysis of histopathologic observations to date and review the reported findings.

Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross-sectional study (2016-2017).

BACKGROUND AND AIMS: Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1-signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. METHODS: Formalin-fixed, paraffin-embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer-related genes was sequenced in the RNAlater samples. RESULTS: Ninety-one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51-70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1-signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. CONCLUSIONS: The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted.

Correction to: Low-cost HPV testing and the prevalence of cervical infection in asymptomatic populations in Guatemala.

Following publication of the original article [1], an error was reported in the tagging of Joël Fokom Domgue in the author group. The tagging in this correction article has been fixed.

Tuberculosis en estudios post mortem: estudio observacional de 10 años en el Hospital General San Juan de Dios, Guatemala / Post mortem examination in tuberculosis: A 10 year observational study in the San Juan de Dios General Hospital, Guatemala

Introducción: La tuberculosis constituye un problema importante de salud a nivel mundial y más aún, la detección temprana y el tratamiento adecuado de la misma en países subdesarrollados. Los estudios post mortem (EPM) han permitido el diagnóstico de tuberculosis, aún en casos sin diagnóstico clínico de la enfermedad. Objetivo: Conocer el número de casos con diagnóstico de tuberculosis en EPM, durante un período de 10 años, en el Hospital General San Juan de Dios (HGSJDD) de Guatemala. Material y métodos: Se revisaron los informes finales de EPM del HGSJDD de Guatemala, de abril del 2006 a marzo del 2016. Se identificaron los casos con diagnóstico de tuberculosis y se revisaron cortes histológicos y tinciones especiales de los mismos. Resultados: En los 10 años revisados, se realizaron 859 EPM, en 21 casos se diagnosticó tuberculosis, 18 en adultos y 3 en niños. La mayoría correspondió a tuberculosis pulmonar (80,95%). En ninguno de los casos se había realizado el diagnóstico clínico de tuberculosis y solo en 5 se tuvo sospecha clínica de la enfermedad, pero ninguno fue investigado. Ningún paciente tenía documentado VIH/sida. Conclusión: El EPM sigue siendo de importancia en el estudio de las enfermedades. En el presente estudio se encontró el diagnóstico de 21 casos de tuberculosis, que no se habían diagnosticado en las evaluaciones clínicas

Introduction: Tuberculosis is a very important health problem worldwide. Early detection and adequate treatment of this disease is also a problem in low income countries. Post mortem examination has enabled tuberculosis to be diagnosed, even in cases without a clinical diagnosis of the disease. Objective: To determine the number of tuberculosis cases diagnosed on autopsy during a period of 10 years, at the San Juan de Dios General Hospital, Guatemala (SJDGH). Material and methods: The final autopsy reports at the between April 2006 and March 2016 were reviewed. H&E and special stains in cases with a diagnosis of tuberculosis were revised for confirmation. Results: During the 10 years reviewed, 859 autopsies had been carried out, 21 of which had the diagnosis of tuberculosis; 18 were adults and 3 were children and the majority (80.95%) were cases of pulmonary tuberculosis. However, in only 5 cases had there been a clinical suspicion, but without further investigation and none had a confirmed clinical diagnosis of tuberculosis. No patients had documented HIV/AIDS. Conclusion: Autopsy continues to be important in the study of disease. In this retrospective study, 21 cases of tuberculosis in 21 cases were found in patients with no clinical diagnosis of the disease

[Post mortem examination in tuberculosis: A 10 year observational study in the San Juan de Dios General Hospital, Guatemala]. / Tuberculosis en estudios post mortem: estudio observacional de 10 años en el Hospital General San Juan de Dios, Guatemala.

INTRODUCTION: Tuberculosis is a very important health problem worldwide. Early detection and adequate treatment of this disease is also a problem in low income countries. Post mortem examination has enabled tuberculosis to be diagnosed, even in cases without a clinical diagnosis of the disease. OBJECTIVE: To determine the number of tuberculosis cases diagnosed on autopsy during a period of 10 years, at the San Juan de Dios General Hospital, Guatemala (SJDGH). MATERIAL AND METHODS: The final autopsy reports at the between April 2006 and March 2016 were reviewed. H&E and special stains in cases with a diagnosis of tuberculosis were revised for confirmation. RESULTS: During the 10 years reviewed, 859 autopsies had been carried out, 21 of which had the diagnosis of tuberculosis; 18 were adults and 3 were children and the majority (80.95%) were cases of pulmonary tuberculosis. However, in only 5 cases had there been a clinical suspicion, but without further investigation and none had a confirmed clinical diagnosis of tuberculosis. No patients had documented HIV/AIDS. CONCLUSION: Autopsy continues to be important in the study of disease. In this retrospective study, 21 cases of tuberculosis in 21 cases were found in patients with no clinical diagnosis of the disease.

Melanoma primario de vejiga urinaria: presentación de caso / Primary melanoma of the bladder. A case report

Los melanomas de vejiga urinaria son poco frecuentes. Presentamos el caso de una paciente femenina de 58 años, quien consultó por disuria y hematuria de 4 meses de evolución. Se le realizó cistoscopia y biopsia, la cual fue interpretada como melanoma invasivo. Posteriormente se realizó cistectomía parcial, en la cual se diagnosticó melanoma, confirmado por positividad de las células neoplásicas para Melan-A y HMB-45 en estudio de inmunohistoquímica. Se demostró invasión neoplásica de todo el espesor de la capa muscular y de bordes quirúrgicos. Cuatro meses después se recibió vejiga urinaria de 13×7×5cm, en la cual se encontró, además del melanoma, melanosis y nevo melanocítico en vejiga urinaria. El nevo melanocítico se demostró mediante positividad a anticuerpos melanocíticos, de células no atípicas en capa basal de urotelio vecino y distante al tumor. La paciente sobrevivió 9 meses

Primary melanoma of the urinary bladder is rare. We report a case of a 58-year-old woman, who presented with a 4 month history of dysuria and hematuria. A biopsy indicated a diagnosis of invasive melanoma and a partial cystectomy was performed. The neoplasm had invaded the entire thickness of the bladder wall and the neoplastic cells were positive for Melan A and HMB-45. Four months later a urinary bladder measuring 13×7×5cm was sent for histopathology. Melanoma, melanosis and a melanocytic nevus were seen; the latter was confirmed by the positivity to melanocytic markers of non-atypical cells in both the urothelial basal layer and areas distant from the tumour. The patient died nine months later

[Primary melanoma of the bladder. A case report]. / Melanoma primario de vejiga urinaria: presentación de caso.

Primary melanoma of the urinary bladder is rare. We report a case of a 58-year-old woman, who presented with a 4 month history of dysuria and hematuria. A biopsy indicated a diagnosis of invasive melanoma and a partial cystectomy was performed. The neoplasm had invaded the entire thickness of the bladder wall and the neoplastic cells were positive for Melan A and HMB-45. Four months later a urinary bladder measuring 13×7×5cm was sent for histopathology. Melanoma, melanosis and a melanocytic nevus were seen; the latter was confirmed by the positivity to melanocytic markers of non-atypical cells in both the urothelial basal layer and areas distant from the tumour. The patient died nine months later.

Low-cost HPV testing and the prevalence of cervical infection in asymptomatic populations in Guatemala.

BACKGROUND: A low cost and accurate method for detecting high-risk (HR) human papillomavirus (HPV) is important to permit HPV testing for cervical cancer prevention. We used a commercially available HPV method (H13, Hybribio) which was documented to function accurately in a reduced volume of cervical specimen to determine the most prevalent HPV types and the distribution of HPV infections in over 1795 cancer-free women in Guatemala undergoing primary screening for cervical cancer by cytology. METHODS: HR-HPV detection was attempted in cervical samples from 1795 cancer-free women receiving Pap smears using the Hybribio™ real-time PCR assay of 13 HR types. The test includes a globin gene internal control. HPV positive samples were sequenced to determine viral type. Age-specific prevalence of HPV was also assessed in the study population. RESULTS: A total of 13% (226/1717) of women tested HPV+, with 78 samples (4.3%) failing to amplify the internal control. The highest prevalence was found in younger women (< 30 years, 22%) and older ones (≥60 years, 15%). The six most common HR-HPV types among the 148 HPV+ typed were HPV16 (22%), HPV18 (11%), HPV39 (11%), HPV58 (10%), HPV52 (8%), and HPV45 (8%). CONCLUSIONS: In this sample of cancer free women in Guatemala, HPV16 was the most prevalent HR type in Guatemala and the age-specific prevalence curve peaked in younger ages. Women in the 30-59-year age groups had a prevalence of HR-HPV of 8%, however, larger studies to better describe the epidemiology of HPV in Guatemala are needed.

Prevalencia de enfermedades infecciosas crónicas en autopsias clínicas / Prevalence of chronic infectious diseases in clinical autopsies

Las enfermedades infecciosas crónicas constituyen un problema de salud pública mundial al ser importante causa de mortalidad. En Guatemala no existen estudios postmortem recientes que aborden dicho tema, por lo que se desconoce su prevalencia en autopsias clínicas del país. El presente estudio se delimita las siguientes enfermedades: tuberculosis, candidiasis, neurocisticercosis, aspergilosis, coccidioidomicosis e histoplasmosis. Objetivo: determinar la prevalencia de las enfermedades infecciosas crónicas en autopsias clínicas. Material y Métodos: investigación descriptiva retrospectiva, basada en los datos de 909 boletas de protocolos completos de autopsias clínicas realizadas del año 2006 al 2015 en el Departamento de patología en el Hospital General San Juan de Dios de Guatemala

La importancia de las publicaciones científicas en el ranking de las universidades: reto para una universidad pública / The importance of scientific publications on the ranking of universities: challenge for a public university

Antecedentes: La evaluación de la excelencia académica de las universidades toma en cuenta varios indicadores, uno de los más determinantes es la investigación científica, que a su vez es usualmente medida por el número y el impacto de las publicaciones en revistas indexadas. Las universidades necesitan saber su posición en relación al resto de universidades del mundo para desarrollar planes de mejoramiento. Objetivo: estimar cuánto del crédito por investigación que la Universidad de San Carlos de Guatemala (USAC) merece, pudiera estar siendo detectado y evaluado por las entidades dedicadas a estratificar las universidades según su rendimiento académico. Material y método: estudio exploratorio de datos obtenidos de PUBMED sobre artículos científicos atribuibles a la USAC, publicados antes del 2017. Los datos bibliométricos analizados incluyeron la cantidad de artículos y el número de citas por articulo...(AU)

Guías de diagnóstico y tratamiento de la diabetes gestacional. ALAD, 2016 / Guidelines of diagnosis and treatment of gestational diabetes. Alad, 2016

En los últimos años el aumento de la prevalencia de obesidad y diabetes mellitus tipo 2 (DM2), la aparición a edades más tempranas de DM2, así como el desplazamiento del embarazo a edades mayores conllevan a un aumento de casos de diabetes (DM) en el embarazo. En algunas pacientes la diabetes no se diagnostica y obviamente no se trata. Este hecho puede complicar un embarazo, especialmente en el período embriogénico. La aplicación de nuevos criterios de diagnóstico para la diabetes gestacional, la controversia en el uso y la seguridad de los antidiabéticos orales durante el embarazo, así como el uso de determinados análogos de insulina hacen indispensable que Latinoamérica, a través del Grupo de Trabajo de Diabetes y Embarazo de la Asociación Latinoamericana de Diabetes (ALAD), actualice sus recomendaciones. El desarrollo de las mismas se realizó en varias reuniones y trabajo conjunto del grupo. Se tuvo en cuenta el grado de nivel de evidencia, la experiencia de los referentes y la adaptación cultural según las regiones donde se implementarán las recomendaciones descriptas

La producción científica / The scientific production

Desde hace siglos el acopio de información en el mundo ha sido prioritario. En investigación científica, esto es fundamental. Con el aparecimiento de Internet y las redes sociales, la tarea de reunir en un portal y poner a disposición de los investigadores, universidades, autoridades académicas, centros especializados, etc., los conocimientos generados en cualquier área del planeta, se ha facilitado; aunque mucha información aún se encuentra "encriptada", es decir, los buscadores específicos no la logran encontrar. En este artículo abordamos la producción científica, la inversión en ciencia y tecnología y los buscadores de publicaciones e investigadores.

The search and storage of information havebeen crucial in the world throughout history.These processes are fundamental in scienceresearch. With the widespread use of internetand social media, the task of gathering informationin websites of free access, has made it easyfor researchers, universities, specialized centers,academic authorities, etc., to analyzeknowledge generated in any place of the world.Much information is still unavailable (encrypted)to scientific production browsers. In this paperwe describe the scientific production, investmentin science and technology and browsers ofresearch publications and researchers.

Un vistazo a la producción guatemalteca de publicaciones médicas / A glance at the guatemalan production of medical publications

Antecedentes: Aunque se asume que Guatemala,como país, publica poco en revistasacadémicas internacionalmente catalogadascomo prestigiosas, se desconocen estudios quenos aporten cifras concretas sobre su producciónde publicaciones médicas. Objetivo:Conocer la producción de publicaciones médicasde Guatemala y su aporte a la producciónuniversal, de Latinoamérica y de Centroamérica.Material y Método: Investigación “secundaria”basada en los datos crudos disponibles en laplataforma de acceso libre denominada “TheSCImago Journal & Country Rank”. Resultados:La producción de publicaciones médicas deGuatemala ha sido de aproximadamente 40documentos por año durante los últimos 24años.

Antecedents: Even though it is assumed thatGuatemala, as a country, publishes little in medicaljournals internationally ranked, no studiesare known that show actual numbers on theproduction of medical publications. Objective:To find out Guatemala’s production of medicalpublications and the contribution of that productionto the total production of the world, of LatinAmerica and of Central America. Material yMethod: This is a secondary research that analyzesrow data available on the free accessplatform denominated “The SCImago Journal &Country Rank”. Results: The production of medicalpublications by Guatemala has been about40 documents per year during the last 24 years.

Tumores del estroma gastrointestinal / Gastrointestinal stromal tumors

Antecedentes: Los tumores del estroma gastrointestinal (TEG) son los tumores mesenquimales más comunes del tracto gastrointestinal (TGI), se considera que surgen de las células de Cajal, ocurren principalmente en adultos mayores (60-65 años) y se localizan en estómago (50%-70%), intestino delgado (25%-35%), colon-recto (5%-10%) y esófago (<5%). La mayoría se presenta de manera esporádica y hasta el 70% son clínicamente sintomáticos. El diagnóstico definitivo se realiza en el estudio anatomopatológico. El pronóstico de estos tumores se determina por el tamaño, recuento mitótico y localización del tumor, clasificandose: riesgo muy bajo, riesgo bajo, riesgo intermedio y riesgo alto. La cirugía es la opción terapéutica principal...

Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract (GI), areconsidered to arise from the Cajal cells. Theyoccur mainly in older adults, 60-65 years. Theypresent in the stomach (50%-70%), small intestine (25%-35%), colon and rectum (5%-10%)and esophagus (<5%). Most GISTs are sporadicand are clinically symptomatic. The definitivediagnosis is made through anatomic pathology study. To determine the prognosis of this type of tumors we use the size, mitotic count and location of the tumor, classified them in: very low risk, low risk, intermediate risk and high risk. Surgery is the main treatment...

Neurocisticercosis en Guatemala / Neurocysticercosis in Guatemala

La neurocisticercosis es causa de epilepsia tardía en muchos países, principalmente en los países en vías de desarrollo. Se adquiere al ingerir huevos de Taenia solium en alimentos y agua contaminados. La Taenia solium se adquiere ingiriendo el cisticerco, cuando consumimos carne de cerdo mal cocida. Presentamos los hallazgos de 30 pacientes operados en el Hospital General San Juan de Dios de la ciudad de Guatemala, de junio 2007 a junio 2012, de los cuales 17 son del sexo femenino y 13 del sexo masculino; el rango de edad fue de 11 a 65 años y la década de mayor presentación fue de 21 a 30 años (12 pacientes). Se revisaron los expedientes de 18 pacientes, encontrando que las lesiones fueron 7 en parénquima, 7 intraventriculares y 4 subaracnoideas. Los síntomas más referidos fueron náuseas, cefalea y vómitos. El diagnóstico por imagen se hizo en 11 casos por tomografía axial computarizada y en 7 por resonancia magnética. En 3 hubo eosinofilia. Se realizó la clasificación histológica del estadio del cisticerco, encontrando 12 en el estadio vesicular, 5 en el estadio vesicular coloidal, 12 en el estadio granular nodular y uno en el estadio calcificado (AU)

Neurocysticercosis causes late epilepsy in many countries, but mainly in developing countries. It is acquired by ingesting Taenia solium eggs in contaminated food and water. Taenia solium is acquired by the intake of the cysticercus in undercooked pork. We present 30 patients from the General Hospital San Juan de Dios in Guatemala City, who underwent surgery between June 2007 and June 2012. 17 were female and 13 male, the age range was 11-65 years with a majority of patients (12) aged between 21-30 years. We reviewed the records of 18 patients, finding 7 parenchymal lesions, 7 intraventricular lesions, and 4 subarachnoideal lesions. The most frequent symptoms were nausea, vomiting and headaches. Diagnosis by imaging was carried out in 11 cases by CT scan and 7 by MRI. Three patients had eosinophilia. Histological classification was performed to stage the cysticerci: 12 were in the vesicular stage, 5 in the colloidal vesicular stage, 12 in the granular nodular stage and 1 in the calcified stage (AU)