Tumor espermatocítico variante anaplásica sincrónico bilateral: reporte de una neoplasia infrecuente / Bilateral synchronous anaplastic variant spermatocytic tumor: Report of a rare neoplasm

El tumor espermatocítico es una neoplasia testicular de células germinales, muy infrecuente, que representa menos del 1% de los cánceres testiculares. Afecta generalmente a hombres mayores con una edad media de 53,6 años (rango 19-92 años). El tumor espermatocítico se clasifica dentro del grupo de tumores germinales no relacionados con la neoplasia de células germinales in situ. Muestra características clinicopatológicas diferentes del seminoma clásico y no se considera una variante de este último. Debido a una superposición morfológica con el seminoma clásico, en el pasado se denominó «seminoma espermatocítico». La variante anaplásica del tumor espermatocítico es excepcional, se han descrito pocos casos en la literatura, presenta un inicio más temprano en comparación con el tumor espermatocítico y un buen comportamiento a pesar de mostrar patrones histológicos similares al seminoma clásico. Presentamos el segundo caso de tumor espermatocítico anaplásico sincrónico bilateral, en un paciente joven tratado con orquiectomía y quimioterapia. (AU)

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called “sperm cell seminoma” in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy. (AU)

[Bilateral synchronous anaplastic variant spermatocytic tumor: Report of a rare neoplasm]. / Tumor espermatocítico variante anaplásica sincrónico bilateral: reporte de una neoplasia infrecuente.

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called "sperm cell seminoma" in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy.

Pregnancy in women with dilated cardiomyopathy genetic variants.

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

Variants of posterior semicircular canal involvement in benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo is the most common cause of peripheral vertigo. It is characterized by short and recurrent episodes of vertigo, trigged by specific head movements that displace otoconia within the semicircular canals. The movement of dislodge otoconia from the utricle cause abnormal positional endolymphatic currents. Primary treatment involves reposition maneuvers aimed at moving the displaced otoconia out the affected canal, therefore correct identification of the affected canal is essential for the diagnosis. The posterior semicircular canal (PSC) is the most frequently affected due to its spatial orientation and the force of gravity. Recent technological advances have allowed for better assessment of positional nystagmus during diagnostic and therapeutic maneuvers, revealing various possible scenarios of PSC involvement. Regarding the PSC, otoconia may be found in different parts of the canal, and not just in the expected location, floating in the long arm of the canal. The understanding of these variants is crucial, as the prognosis and the disease progression differ in such cases. This review aims to describe the six possible variants of PSC involvement described so far.

Efecto de la variante Ómicron sobre la incidencia y la letalidad durante la 6 onda epidémica COVID-19 en España / Effect of the Omicron variant on cumulative incidence of infection and lethality during the sixth wave of the COVID-19 epidemic in Spain

La pandemia COVID-19 ha puesto a prueba los sistemas sanitarios a nivel mundial. Las sucesivas ondas epidémicas han mostrado características diferentes. La variante Ómicron del SARS-CoV-2 modificó el comportamiento epidémico que habían seguido las variantes previas. El objetivo de este análisis fue determinar las características epidemiológicas de la COVID-19 durante la 6.ª onda epidémica y sus diferencias según predominara las variantes Delta u Ómicron. Se analizaron los datos epidemiológicos correspondientes a la 6.ª onda epidémica publicados por los organismos oficiales, y se analizaron la incidencia acumulada de infección (IA-I) y las tasas de letalidad (TL), tanto del conjunto de España como de las diferentes Comunidades Autónomas, en el conjunto de la población y por grupos etarios. Los resultados mostraron que la IA-I era mayor con la variante Ómicron (10,89 vs. 0,75% con Delta) mientras que la TL lo era con la variante Delta (4,2 vs. 1,3‰ con Ómicron), así como una mayor tasa de hospitalización e ingreso en UCI con la variante Delta.(AU)

The COVID-19 pandemic has strained healthcare systems globally. The successive epidemic waves have shown different characteristics. The Omicron variant of SARS-CoV-2 modified the epidemic behavior that previous variants had followed. The aim of this analysis was to determine the epidemiological characteristics of COVID-19 during the sixth epidemic wave and its differences according to the predominance of the Delta or Omicron variants. The epidemiological data corresponding to the sixth wave of the epidemic published by official organizations were analyzed, and the cumulative incidence of infection (CI-I) and case fatality rates (CFR) were calculated, both for Spain as a whole and for the different Autonomous Communities, in the population as a whole and by age groups. The results showed that the CI-I was higher with the Ómicron variant (10.89% vs 0.75% with Delta) while the CFR was higher with the Delta variant (4.2‰ vs 1.3‰ with Ómicron), as well as a higher rate of hospitalization and ICU admission with the Delta variant.(AU)

Utilidad del complejo posterior para el diagnóstico prenatal de sintelencefalia

Introducción y objetivo: Demostrar el valor del plano axial del complejo posterior, como apoyo a la detección antenatal de sintelencefalia, variante de holoprosencefalia. Método: Se incluyeron todas las pacientes con diagnóstico de sintelencefalia evaluadas desde el año 2008. En todos los casos se consignaron los datos clínicos, de neurosonografía (NSG), de resonancia magnética (RM) y genética. Resultados: Cuatro casos fueron diagnosticados en el segundo trimestre y en todos se realizó estudio genético y RM. Tres tuvieron en su evolución anomalías extra-SNC y dos de ellos alteraciones cromosómicas, una de ellas incompatible con la vida extrauterina. Lo hallazgos descritos en neuroimagen para esta afección fueron detectados en la NSG, con una excelente correlación con RM, ya fuera esta última realizada en periodo fetal o posnatal. Conclusión: El diagnóstico prenatal de variantes de holoprosencefalia es difícil, considerando la existencia de una fusión medial más acotada que en las formas clásicas. El presente estudio demuestra la utilidad del plano del complejo posterior para la sospecha diagnóstica de sintelencefalia.

Introduction and objective: To demonstrate the value of the axial plane of the posterior complex, as a clue for the antenatal detection of synthelencephaly, a variant of holoprosencephaly. Method: All patients diagnosed with syntelencephaly evaluated since 2008 were included. In all cases, clinical, neurosonography (NSG), magnetic resonance imaging (MRI) and genetic data were recorded. Results: Four cases were diagnosed in the second trimester and in all of them a genetic study and MRI were performed. Three had extra-CNS anomalies in their evolution and two of them chromosomal anomalies, one of them incompatible with extrauterine life. Neuroimaging findings described for this condition were detected by NSG, with an excellent correlation with MRI, whether the latter was performed in the fetal or postnatal period. Conclusion: The prenatal diagnosis of holoprosencephaly variants is difficult, considering the existence of a more limited medial fusion than in the classical forms. The present study demonstrates the usefulness of the posterior complex plane for the diagnostic suspicion of synthelencephaly.

[Effect of the Omicron variant on cumulative incidence of infection and lethality during the sixth wave of the COVID-19 epidemic in Spain]. / Efecto de la variante Ómicron sobre la incidencia y la letalidad durante la 6.ª onda epidémica COVID-19 en España.

The COVID-19 pandemic has strained healthcare systems globally. The successive epidemic waves have shown different characteristics. The Omicron variant of SARS-CoV-2 modified the epidemic behavior that previous variants had followed. The aim of this analysis was to determine the epidemiological characteristics of COVID-19 during the sixth epidemic wave and its differences according to the predominance of the Delta or Omicron variants. The epidemiological data corresponding to the sixth wave of the epidemic published by official organizations were analyzed, and the cumulative incidence of infection (CI-I) and case fatality rates (CFR) were calculated, both for Spain as a whole and for the different Autonomous Communities, in the population as a whole and by age groups. The results showed that the CI-I was higher with the Ómicron variant (10.89% vs 0.75% with Delta) while the CFR was higher with the Delta variant (4.2‰ vs 1.3‰ with Ómicron), as well as a higher rate of hospitalization and ICU admission with the Delta variant.

La genética de la epilepsia en la práctica clínica / The genetics of epilepsy in the clinical practice

Resumen La epilepsia es un trastorno neurológico caracterizado por crisis epilépticas recurrentes no provocadas, en el cual la genética tiene un factor etiológico importante. Durante las últimas décadas se ha logrado encontrar genes específicos involucrados en la patogénesis de esta condición. Actualmente existen múltiples exámenes disponibles en la práctica clínica para el diagnóstico genético, siendo los más útiles los paneles multi-genes y la secuenciación del exoma completo por medio de next generation sequencing (NGS). El tener un diagnósti co genético puede mejorar la calidad de vida de cada paciente y su familia, al mismo tiempo que nos ayuda a individualizar el tratamiento haciéndolo más eficaz. Algunos ejemplos en los que el diagnóstico genético puede modificar la conducta terapéutica incluyen el gen SCN1A en que se recomienda no utilizar medicamentos bloqueadores de canales de sodio y el gen SLC2A1 en el que se recomienda el inicio de la dieta cetogénica. El futuro de la investigación en medicina de precisión en epilepsia es muy prometedor, con el objetivo de que cada paciente reciba un tratamiento acorde a su etio logía genética.

Abstract Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. It is known that genetics play an important etiology roll. During the last decades it has been possible to find specific genes involved in the pathogenesis of this condition. There are currently multiple studies available in clinical practice for genetic diagnosis, the most useful being the next generation se quencing (NGS) techniques with multi-gene panels and whole exome sequencing. Having a genetic diagnosis can help improve the quality of life of each patient and their family, while it helps us to individualize the treatment, making it more effective. Some examples in which ge netic diagnosis can modify therapeutic conduct include the SCN1A gene, in which it is recommended not to use drugs that block Sodium channels, and the SLC2A1 gene, in which starting ketogenic diet is recommended. The future of precision medicine research in epilepsy is very promising, with the goal that each patient receives treatment according to their genetic etiology.

D313Y variant in two related end-stage renal disease patients – Pathogenic or not yet? / Dos pacientes con enfermedad renal terminal con la variante de significado incierto D313Y: ¿patógena o aún no?

Fabry disease is a multisystem lysosomal storage disorder caused by mutations in the GLA gene that result in a deficient or absent activity of alpha-galactosidase A. There is a wide spectrum of GLA gene variants, some of which are described as non-pathogenic. The clinical importance of the D313Y variant is still under debate, although in recent years it has been considered as a variant of unknown significance or a benign variant. Despite this prevailing notion, there are multiple case reports of patients with D313Y variant that presented signs and symptoms consistent with FD without any other etiological explanation. In this article, we present two family members with an important renal phenotype and other typical manifestations of FD (white matter lesions and left ventricular hypertrophy) that only had the D313Y variant. These cases suggest that this variant of unknown significance may contribute to the development of common features of FD and should not be undervalued. (AU)

La enfermedad de Fabry (EF) es un trastorno de almacenamiento lisosómico multisistémico causado por mutaciones en el gen GLA que tienen como resultado una actividad deficiente o ausente de alfa-galactosidasa A. Existe un amplio espectro de variantes del gen GLA, algunas de las cuales se describen como no patógenas. La importancia clínica de la variante D313Y aún está en debate, aunque en los últimos años se ha considerado una variante de significado incierto o una variante benigna. A pesar de esta noción predominante, existen múltiples reportes de casos de pacientes con variante D313Y que presentaron signos y síntomas consistentes con EF sin ninguna otra explicación etiológica. En este artículo presentamos 2 familiares con un importante fenotipo renal y otras manifestaciones típicas de la EF (lesiones de la sustancia blanca e hipertrofia ventricular izquierda) que solo presentaban la variante D313Y. Estos casos indican que esta variante de significado incierto puede contribuir al desarrollo de características comunes de la EF y no debe subestimarse. (AU)

Un caso de hipocolesterolemia a estudio / A case of hypocholesterolemia under study

Las hipocolesterolemias primarias (o hipobetalipoproteinemias) constituyen un trastorno infrecuente del metabolismo de las lipoproteínas que pueden obedecer a una predisposición poligénica o a una enfermedad monogénica. Entre estas, es posible diferenciar entre formas sintomáticas y asintomáticas, en las que, en ausencia de causas secundarias, la sospecha clínica inicial son concentraciones plasmáticas de ApoB por debajo del percentil 5 de la distribución por edad y sexo. En esta nota clínica describimos del diagnóstico diferencial de un caso de hipocolesterolemia asintomática. Estudiamos los datos clínicos de la paciente índice, así como su perfil lipídico y el de los familiares junto con los datos clínicos de estos que son relevantes para realizar el diagnóstico diferencial. Se realizó un estudio genético como prueba diagnóstica. El diagnóstico diferencial realizado sugirió una hipobetalipoproteinemia heterocigota por variantes de pérdida de función en PCSK9. La prueba diagnóstica puso de manifiesto, en la paciente índice, la presencia de una variante de cambio de pauta de lectura en PCSK9, en heterocigosis, de origen materno. Las concentraciones plasmáticas de colesterol de LDL y PCSK9 de la paciente y los familiares, fueron compatibles con la segregación de dicha variante. En conclusión, la prueba diagnóstica realizada permitió confirmar el diagnóstico de sospecha en el caso estudiado de hipobetalipoproteinemia familiar asintomática a causa de una variante de pérdida de función en el gen PCSK9. (AU)

Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband's clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene. (AU)

A case of hypocholesterolemia under study. / Un caso de hipocolesterolemia a estudio.

Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband's clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene.

Ayudas diagnósticas y diagnóstico diferencial de la enfermedad de Pompe / Diagnostic aids and differential diagnosis of Pompe disease

Introducción: La enfermedad de Pompe (EP) o glucogenosis tipo II es una enfermedad autosómica recesiva causada por mutaciones en el gen GAA que codifica para la proteína alfa-1,4-glucosidasa. Su deficiencia lleva a un almacenamiento anormal de glucógeno en los lisosomas de varias células, a través de los diferentes tejidos, lo que causa un compromiso musculoesquelético predominante. Contenidos: Los fenotipos de la enfermedad dependen de las variantes genéticas y de los niveles de la actividad enzimática residual. La enfermedad se presenta como EP de inicio infantil, EP de inicio tardío y EP intermedio, por lo que es de suma importancia su diagnóstico temprano, por medio de estudios moleculares como la secuenciación de Sanger y la secuenciación de nueva generación. Conclusiones: Se ha demostrado, mediante diferentes estudios, que las variaciones genéticas pueden diferir entre etnias, y es importante su caracterización molecular para determinar el tratamiento más adecuado, de acuerdo con el estado del material inmunológico de reacción cruzada (CRIM).

Introduction: Pompe disease (PD) or Glycogenosis Type II is a rare autosomal recessive disease caused by mutations in the GAA gene that codes for the alpha-1,4-glucosidase protein. Its deficiency leads to abnormal glycogen storage in the lysosomes of various cells throughout the different tissues causing a predominant musculoskeletal compromise. Contents: The phenotypes of the disease depend on the genetic variants and the levels of residual enzyme activity, presenting as infantile-onset PD, late-onset PD, and intermediate PD; Therefore, early diagnosis of the disease through molecular studies such as Sanger sequencing and new generation sequencing is of utmost importance. Conclusions: It has been shown through different studies that genetic variations can vary between ethnic groups and the molecular characterization of the variants is important to determine the most appropriate treatment depending on the state of the cross-reactive immunological material (CRIM)

Effect of non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP) terminology on surgical management concepts / La importancia de la terminología en el tratamiento de la neoplasia folicular no invasiva de tiroides con características de tipo papilar

Background: Despite the strict diagnostic criteria recently proposed for non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP), its incidence is still unknown. Employing a retrospective analysis of the follicular variant of papillary thyroid carcinoma (FVPTC), we investigated the diagnosis, prevalence and postoperative course of NIFTP. Methods: We examined retrospectively the records of 112 patients who had undergone thyroid surgery and had a postoperative diagnosis of FVPTC at our hospital from 2010 to 2021. All clinical, radiologic, and pathologic features were evaluated. Results: Only 34 (27.9%) patients met the strict pathologic criteria for NIFTP; 11 cases having been diagnosed as NIFTP initially and 23 after re-evaluation of histopathologic slides. None of the 11 NIFTP patients underwent a 2-stage operation, in contrast to 10 (29.4%) patients initially diagnosed as FVPTC who had a completion thyroidectomy after the initial hemithyroidectomy. The median follow-up was 14.5 (ranging from 0 to 78) months. None of the cases developed a recurrence. Conclusion: To avoid unnecessary treatment or the follow-up advised for papillary thyroid carcinoma, clinicians and pathologists should be familiar with the terminology and the corresponding diagnostic criteria for NIFTP and their impact on management.(AU)

Introducción: A pesar de los definidos criterios diagnósticos recientemente propuestos para la neoplasia folicular de tiroides no invasiva con características de tipo papilar, designada con el acrónimo NIFTP de sus siglas en inglés (non-invasive follicular thyroid neoplasm with papillary-like nuclear features), todavía no se conoce su incidencia real. Empleando un análisis retrospectivo de la variante folicular de carcinoma papilar de tiroides (VFCPT), investigamos el diagnóstico, la prevalencia y el curso postoperativo de la NIFTP. Método: Examen retrospectivo de archivos de 112 pacientes operados de tiroides, y que tenían un diagnóstico postoperatorio de VFCPT en nuestro centro entre los años 2010 y 2021. Se evaluaron todos los datos clínicos, radiológicos e histopatológicos. Resultados: Solo 34 (27,9%) pacientes cumplían los criterios patológicos estrictos de NIFTP; 11 casos habían sido diagnosticados inicialmente y 23 después de una reevaluación de las láminas histopatológicas. Ninguno de los 11 casos iniciales de NIFTP fue sometido a una operación de 2 etapas, sin embargo, en 10 (29,4%) de los pacientes diagnosticados primero como VRCPT se practicó una tiroidectomía completa después de la hemitiroidectomía inicial. El seguimiento medio fue de 14,5 meses (entre 0 y 78 meses). Ningún paciente desarrolló recidivas. Conclusión: Para evitar un tratamiento excesivo o seguimiento tradicional aconsejado para el carcinoma papilar de tiroides, tanto los clínicos como los anatomopatólogos deben familiarizarse con la terminología y los criterios diagnósticos de la NIFTP, y como estos influencian en el tratamiento.(AU)

Validation of a new strategy for the identification of SARS-CoV-2 variants by sequencing the spike gene by Sanger.

INTRODUCTION: The emergence of multiple variants of SARS-CoV-2 during the COVID-19 pandemic is of great world concern. Until now, their analysis has mainly focused on next-generation sequencing. However, this technique is expensive and requires sophisticated equipment, long processing times, and highly qualified technical personnel with experience in bioinformatics. To contribute to the analysis of variants of interest and variants of concern, increase the diagnostic capacity, and process samples to carry out genomic surveillance, we propose a quick and easy methodology to apply, based on Sanger sequencing of 3 gene fragments that code for protein spike. METHODS: Fifteen positive samples for SARS-CoV-2 with a cycle threshold below 25 were sequenced by Sanger and next-generation sequencing methodologies. The data obtained were analyzed on the Nextstrain and PANGO Lineages platforms. RESULTS: Both methodologies allowed the identification of the variants of interest reported by the WHO. Two samples were identified as Alpha, 3 Gamma, one Delta, 3 Mu, one Omicron, and 5 strains were close to the initial Wuhan-Hu-1 virus isolate. According to in silico analysis, key mutations can also be detected to identify and classify other variants not evaluated in the study. CONCLUSION: The different SARS-CoV-2 lineages of interest and concern are classified quickly, agilely, and reliably with the Sanger sequencing methodology.

Validación de una nueva estrategia para la identificación de variantes de SARS-CoV-2 mediante secuenciación del gen espiga por Sanger / Validation of a new strategy for the identification of SARS-CoV-2 variants by sequencing the spike gene by Sanger

Introducción: La aparición de múltiples variantes del SARS-CoV-2 durante la pandemia de COVID-19 es motivo de gran preocupación mundial. Hasta el momento, su análisis se ha centrado principalmente en la secuenciación de nueva generación. Sin embargo, esta técnica es costosa y requiere equipos sofisticados, largos tiempos de procesamiento y personal técnico altamente cualificado con experiencia en bioinformática. Para contribuir al análisis de variantes de interés y de preocupación, aumentar la capacidad diagnóstica y procesar muestras para realizar vigilancia genómica, proponemos una metodología rápida y fácil de aplicar, basada en la secuenciación Sanger de 3 fragmentos del gen que codifica para la proteína espiga. Métodos: Se secuenciaron 15 muestras positivas para SARS-CoV-2 con un valor de umbral de ciclo inferior a 25 por metodologías Sanger y secuenciación de nueva generación. Los datos obtenidos fueron analizados en las plataformas Nextstrain y PANGO Lineages. Resultados: Ambas metodologías permitieron identificar las variantes de interés reportadas por la OMS. Se identificaron 2 muestras como alfa, 3 gamma, una delta, tres mu, una ómicron y 5 cepas cercanas al aislado inicial del virus Wuhan-Hu-1. Según el análisis in silico, también se pueden detectar mutaciones clave para identificar y clasificar otras variantes no evaluadas en el estudio. Conclusión: Los diferentes linajes de interés y preocupación de SARS-CoV-2 se clasifican de forma rápida, ágil y fiable con la metodología de secuenciación de Sanger.(AU)

Introduction: The emergence of multiple variants of SARS-CoV-2 during the COVID-19 pandemic is of great world concern. Until now, their analysis has mainly focused on next-generation sequencing. However, this technique is expensive and requires sophisticated equipment, long processing times, and highly qualified technical personnel with experience in bioinformatics. To contribute to the analysis of variants of interest and variants of concern, increase the diagnostic capacity, and process samples to carry out genomic surveillance, we propose a quick and easy methodology to apply, based on Sanger sequencing of 3 gene fragments that code for protein spike. Methods: Fifteen positive samples for SARS-CoV-2 with a cycle threshold below 25 were sequenced by Sanger and next-generation sequencing methodologies. The data obtained were analyzed on the Nextstrain and PANGO Lineages platforms. Results: Both methodologies allowed the identification of the variants of interest reported by the WHO. Two samples were identified as Alpha, 3 Gamma, one Delta, 3 Mu, one Omicron, and 5 strains were close to the initial Wuhan-Hu-1 virus isolate. According to in silico analysis, key mutations can also be detected to identify and classify other variants not evaluated in the study. Conclusion: The different SARS-CoV-2 lineages of interest and concern are classified quickly, agilely, and reliably with the Sanger sequencing methodology.(AU)

Effect of non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP) terminology on surgical management concepts.

BACKGROUND: Despite the strict diagnostic criteria recently proposed for non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP), its incidence is still unknown. Employing a retrospective analysis of the follicular variant of papillary thyroid carcinoma (FVPTC), we investigated the diagnosis, prevalence and postoperative course of NIFTP. METHODS: We examined retrospectively the records of 112 patients who had undergone thyroid surgery and had a postoperative diagnosis of FVPTC at our hospital from 2010 to 2021. All clinical, radiologic, and pathologic features were evaluated. RESULTS: Only 34 (27.9%) patients met the strict pathologic criteria for NIFTP; 11 cases having been diagnosed as NIFTP initially and 23 after re-evaluation of histopathologic slides. None of the 11 NIFTP patients underwent a 2-stage operation, in contrast to 10 (29.4%) patients initially diagnosed as FVPTC who had a completion thyroidectomy after the initial hemithyroidectomy. The median follow-up was 14.5 (ranging from 0 to 78) months. None of the cases developed a recurrence. CONCLUSION: To avoid unnecessary treatment or the follow-up advised for papillary thyroid carcinoma, clinicians and pathologists should be familiar with the terminology and the corresponding diagnostic criteria for NIFTP and their impact on management.

Huntington juvenil y fenocopia intrafamiliar a propósito de dos casos / Juvenile Huntington and intrafamily phenocopy, about two cases

RESUMEN La enfermedad de Huntington (EH) es una enfermedad neurodegenerativa hereditaria de progresión irremediablemente fatal. Existen otros trastornos con síntomas semejantes a los de esta enfermedad y que son llamados fenocopias. En nuestro reporte, se presentan los casos de dos hermanos con fenotipo compatible con EH, uno ellos con una fenocopia intrafamiliar, caracterizada por un síndrome coreico y cambios del comportamiento, con estudio genético negativo para EH. El caso índice cursa con una forma parkinsoniana de EH de inicio juvenil, con evolución lentamente progresiva que, además, presenta síntomas neuropsiquiátricos, con respuesta mínima a tratamiento sintomático con psicofármacos. El hermano mayor, caso de fenocopia intrafamiliar, cursó con movimientos discinéticos cervicofaciales y faciales severos, psicosis y cognición conservada. En conclusión, las fenocopias de EH pueden presentarse incluso dentro de una familia con EH genéticamente confirmada. Se recomienda una detallada evaluación neurológica y un estudio genético apropiado en todos los casos en que se tenga sospecha clínica de EH, incluso en familiares directos de pacientes diagnosticados con la enfermedad.

ABSTRACT Huntington's disease (HD) is an inherited neurodegenerative disorder with an always fatal outcome. Other disorders resemble the symptoms of this disease and are called phenocopies. The cases of two brothers in a family affected with a phenotype compatible with HD, are presented, one of them an intrafamilial phenocopy, characterized by choreic syndrome, abnormal behavior, and negative HD genetic testing. The index case evolves with a juvenile-onset slowly progressive parkinsonian form of HD that, in addition, presents neuropsychiatric symptoms with minimal response to symptomatic treatment with dopamine antagonists. The older brother, the intrafamilial phenocopy, experienced severe facial cervicofacial and cervical dyskinetic movements, psychosis, and preserved cognition. In conclusion, the HD phenocopies might occur even within a known, genetically confirmed HD family. It is recommended to perform a detailed neurological examination together with appropriate genetic testing in all cases with clinical suspicious of HD, including direct family members of HD affected individuals.

Comportamiento clínico de la variante oncocítica del cáncer papilar de tiroides: comparación de su evolución frente al cáncer papilar, variantes clásica y de células altas / Clinical behaviour of papillary thyroid cancer oncocytic variant: Stage-matched comparison versus classical and tall cell variant papillary thyroid cancer

Objetivo El cáncer papilar de tiroides (CPT) tiene diferentes variantes y la mayoría de ellas presentan diferencias sutiles. La variante oncocítica (VO) es un subtipo poco frecuente de CPT, sobre el pronóstico de la cual existen resultados controvertidos en la literatura. Investigamos su agresividad y curso clínico comparándolos con la variante clásica (VC) y la variante de células altas (CA) de CPT en diferentes estadios. Material y métodos En este estudio de cohortes retrospectivo se incluyeron: 100 muestras simples de VO, 71 de CA y 1.219 de VC. Las muestras VO se compararon con las VC y las de CA sobre la base de parámetros de pronóstico independientes. La recurrencia de la VO también se comparó estadio por estadio con la VC y CA. Resultados La edad media fue de 46,8 años y la relación hombres/mujeres de 25/75 para la VO. Las tasas de recurrencia en nuestro estudio fueron del 16% en VO; del 13,5% en VC y del 56% en CA. Existe una diferencia estadísticamente significativa con respecto a la recurrencia entre el estadio 1 y el estadio 4 comparando la VO y la VC (p=0,023; p=0,03, respectivamente). También hay una diferencia estadísticamente significativa con respecto a la recurrencia entre el estadio 1 y el estadio 4 comparando la VO y la CA (p=0,001; p=0,024, respectivamente). Se puede suponer que la VO tiene un comportamiento entre la VC y la CA, pero muy cercana a la CA. Conclusión La VO parece ser un poco más agresiva que la VC. A pesar de un tamaño de muestra inadecuado para los estadios 2 y 3, nuestros hallazgos implican un mayor riesgo de recurrencia para la VO que para la VC en los estadios avanzados (estadios 3 y 4) y la VC tiene un pronóstico más desfavorable que VO en estadios precoces (estadios 1 y 2), según el modelo de estadio pareado (AU)

Objective Papillary thyroid cancer (PTC) has many variants and most of them are mild tumors. Oncocytic variant (OV) is a rare subtype of PTC. There are controversial results about its prognosis in the literature. We investigated its aggressivity and clinical course by comparing it with classical variant (CV) and tall cell variant (TV) of PTC over a stage-matched design. Material and methods Pure 100 OV, 71 TV and 1,219 CV were included in this retrospective cohort study. OV was compared with CV and TV according to independent prognostic parameters. OV was also compared stage by stage with CV and TV for recurrence. Results Mean age was 46,8 years and male/female ratio 25/75 for OV. The recurrence rates in our study were 16% in OV, 13,5% in CV and 56% in TV. There is a statistically significant difference according to recurrence between stage 1 and stage 4 OV and CV (P = 0.023, P = 0.03, respectively). There is also a statistically significant difference between stage 1 and stage 4 OV and TV according to recurrence (P = 0.001, P = 0.024, respectively). OV can be supposed to behave between CV and TV, but very closer to CV. Conclusions OV seems to be slightly more aggressive than CV. Despite an inadequate sample size for stage 2 and 3, our findings imply an increased recurrence risk for OV than CV at the advanced stages (stage 3 and 4) and CV has an unfavorable prognosis than OV at early stages (stage 1 and 2) according to stage-matched model (AU)

[Agenesis of the coeliac trunk : A case report]. / Agénésie du tronc cœliaque : à propos d'un cas.

Vascular anatomical variants in general, and of the celiac trunk (TC) in particular, are rarely reported in the literature because they are generally asymptomatic and detected incidentally by imaging examinations performed for other causes. We report a case of agenesis of the celiac trunk, with separate birth of its three branches directly from the abdominal aorta, discovered fortuitously during a CT scan performed as part of the extension assessment of colon adenocarcinoma in a woman. initially asymptomatic.

D313Y variant in two related end-stage renal disease patients - Pathogenic or not yet?

Fabry disease is a multisystem lysosomal storage disorder caused by mutations in the GLA gene that result in a deficient or absent activity of alpha-galactosidase A. There is a wide spectrum of GLA gene variants, some of which are described as non-pathogenic. The clinical importance of the D313Y variant is still under debate, although in recent years it has been considered as a variant of unknown significance or a benign variant. Despite this prevailing notion, there are multiple case reports of patients with D313Y variant that presented signs and symptoms consistent with FD without any other etiological explanation. In this article, we present two family members with an important renal phenotype and other typical manifestations of FD (white matter lesions and left ventricular hypertrophy) that only had the D313Y variant. These cases suggest that this variant of unknown significance may contribute to the development of common features of FD and should not be undervalued.