Somatic Deletion in Exon 10 of Aryl Hydrocarbon Receptor Gene in Human GH-Secreting Pituitary Tumors.

Objective/Purpose: The aryl hydrocarbon receptor (AHR) pathway plays a critical role in the biology of Growth Hormone (GH)-secreting pituitary tumor (somatotropinoma). Germline rs2066853 AHR variant was found to be more frequent among acromegaly patients and associated with a more severe disease with larger invasive somatropinoma, and with resistance to somatostatin analogs treatment in patients living in polluted areas. However, no somatic changes in AHR gene have been reported so far in acromegaly patients. On that basis, the aim of the study was to assess at the somatic level the AHR gene status encompassing exon 10 region, also because of the high rate of variants found in this genomic region. Methods: A cohort of 13 patients aged 20-76 years with biochemical, clinical and histological diagnosis of somatotropinoma was studied. DNA and RNA from pituitary tumor histological samples have been extracted and analyzed by PCR and direct sequencing for AHR gene variants, and compared with corresponding patients' germline DNA as well as normal pituitary tissue as reference control. Results: A degenerated letter codes in the region corresponding to AHR exon 10 (c.1239-c.2056) was detected in somatotropinomas-derived DNA but not in that of matched germline and pituitary normal tissue. By multiple PCR and sequencing analysis, we observed amplification only before codon 1246 and after codon 1254, confirming the presence of a tumor-restricted somatic deletion in the 5' upstream region of AHR exon 10. Analysis of PCR-amplified cDNA revealed a wildtype sequence of exon 9 and 10 in normal pituitary tissue, and a wildtype sequence of exon 9 and 10 up to codon 1246 and no sequence after the deletion region (c.1246-c.1254) in 6 out of 9 tumor samples. Patients carrying the germline rs2066853 AHR variant showed no somatic LOH at the corresponding genetic locus. Conclusion: This is the first demonstration of a recurrent somatic deletion in the exon 10 of the AHR gene in somatotropinomas. The functional impact of this genetic finding needs to be clarified.

Presentación excepcional de herida por arma blanca / Exceptional presentation of a knife wound

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Hybrid treatment of penetrating aortic ulcer.

Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease.

A úlcera aórtica penetrante é uma entidade rara e de prognóstico desfavorável dentro da síndrome aórtica aguda. Mais raros ainda, na literatura, são os casos como o aqui relatado, localizado no arco aórtico, que começa com dor torácica e evolui com disfonia. O presente caso enfatiza o papel da tomografia computadorizada no diagnóstico da úlcera aórtica penetrante e na sua diferenciação de outras entidades dentro da síndrome aórtica aguda. Apresenta também um avanço terapêutico nessa doença, constituído por tratamento híbrido endovascular e cirúrgico.

Hybrid treatment of penetrating aortic ulcer / Tratamento híbrido de úlcera aórtica penetrante

Abstract Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease.

A úlcera aórtica penetrante é uma entidade rara e de prognóstico desfavorável dentro da síndrome aórtica aguda. Mais raros ainda, na literatura, são os casos como o aqui relatado, localizado no arco aórtico, que começa com dor torácica e evolui com disfonia. O presente caso enfatiza o papel da tomografia computadorizada no diagnóstico da úlcera aórtica penetrante e na sua diferenciação de outras entidades dentro da síndrome aórtica aguda. Apresenta também um avanço terapêutico nessa doença, constituído por tratamento híbrido endovascular e cirúrgico.

Revascularización endovascular carotídea realizada por un equipo multidisciplinar: primera experiencia en España / Endovascular carotid revascularization performed by a multidisciplinary team: first experience in Spain

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Microsatellite-based genotyping of Candida parapsilosis sensu stricto isolates reveals dominance and persistence of a particular epidemiological clone among neonatal intensive care unit patients.

In this study, using multilocus microsatellite analysis, we report the genetic characterization of 27 Candida parapsilosis isolates recovered in two different periods of time (2007-2009 and 2011-2012) from infants hospitalized in the neonatal intensive care unit of a hospital in Messina, Italy. The results revealed the persistence and dominance of a particular infectious genotype among NICU patients and highlight the power of the used microsatellite markers in clarifying epidemiologic associations, detect micro-evolutionary variations and facilitating the recognition of outbreaks.

[Cardiologic assessment of surviving family members of young victims of sudden cardiac death: diagnostic yield]. / Screening cardiologico delle famiglie con storia di morte improvvisa giovanile: quali patologie ricercare e con quali strumenti.

Sudden cardiac death (SCD) is one of the most common causes of death in developed countries. In Italy, an annual incidence of 0.7 per 1000 inhabitants per year can be estimated. SCD represents the main cause of sudden death in children, adolescents and young adults and often occurs in young and previously asymptomatic patients. This issue has acquired even greater relevance since implantable cardioverter-defibrillators have proved to be highly effective in preventing sudden death in high-risk subjects. Autopsy findings of young SCD victims include inherited cardiac disorders with a defined morphologic substrate but also hearts without any identifiable structural abnormalities (sudden unexplained death). The potential heritability of the underlying disorder makes surviving relatives at risk of sudden death. A cardiological workup in these families may allow identification of cardiac disease and may unmask affected surviving relatives in whom the disease had remained unrecognized. Cardiological and genetic assessment of relatives of SCD victims based on current literature is reported in this review as well as our experience on SCD in young people in the Lazio Region (Italy) between 2001 and 2008.

Sudden cardiac death in younger adults: autopsy diagnosis as a tool for preventive medicine.

Sudden death in children and younger adults can be caused by potentially heritable cardiovascular disorders, and the fatal outcome is often the first symptom in apparently healthy subjects. In these cases, a careful autopsy becomes the sole diagnostic tool to guide the clinical screening of the families. The aims of the present study were (1) to assess the pathological substrate of sudden cardiac death in children and younger adults (age, 1-40 years) in a large prospective series using strict morphological criteria; and (2) to perform cardiological assessment of the relatives of the deceased subjects with cardiomyopathies or structurally normal hearts, potentially consistent with a heritable cardiac disease. We studied 100 consecutive cases. Autopsy findings included coronary artery disease (30%, atherosclerotic in the majority of cases), cardiomyopathies (22%), and various cardiac abnormalities (28%). In the remaining 20% of cases, the presence of significant morphological abnormalities of the heart was ruled out. Twenty of 42 families in which the heart of the proband was either affected by a cardiomyopathy or failed to show significant structural abnormalities could be contacted and provided informed consent to cardiological assessment. A potentially inherited cardiac disease was diagnosed in 4 (20%). Molecular genetic analysis was restricted to 3 of these families and revealed a mutation in the ryanodine receptor type 2 gene (RyR2) in 1. Our results underline the implication of autopsy findings for relatives and the importance of cardiological screening of family members to uncover familial cardiomyopathies or genetic arrhythmias and to adopt the proper therapeutic and preventive strategies. Genetic testing is still time consuming and costly: accordingly, it should be restricted only to selected cases.

[Value of gated-SPECT in defining the post-revascularization prognosis of patients with ischemic cardiomyopathy]. / Valor del gated-SPECT para definir el pronóstico tras la revascularización en una población con cardiopatía isquémica.

INTRODUCTION AND OBJECTIVES: Gated-SPECT simultaneously evaluates perfusion and ventricular function and could provide important prognostic information in ischemic cardiomyopathy. Our aim was to study the value of gated-SPECT performed before revascularization in a cardioischemic population to predict the outcome of revascularization. METHODS: One hundred and ten patients who had undergone percutaneous (n = 100) or surgical revascularization were included. Patients underwent sestamibi gated-SPECT before revascularization. After revascularization, they were followed-up for at least 12 months (mean 23.7 months, maximum 44 months). We recorded deaths and a combined clinical event of death, non-fatal infarction, and hospital re-admission for cardiac reasons. We analyzed the prognostic value of clinical, angiographic, and gated-SPECT variables. RESULTS: During follow-up, there were 14 deaths (6.4%/ year) and 36 cases of combined events (16.5%/year). Multivariate analysis showed that depressed gated-SPECT ejection fraction (threshold 0.30) was the only variable independently related to death (OR = 4.8; 95%CI, 1.6-14.6) and combined event (OR = 2.5; 95%CI, 1.2-4.8). Survival analysis showed that patients with ejection fraction < or = 0.30% had a significantly shorter period of time free of death (33 months [28-38] versus 42 months [40-44]; p = 0.002) and combined events (28 months [23-32] versus 36 months [33-39]; p = 0.007). CONCLUSIONS: Gated-SPECT, due to the information it provides about left ventricular function, predicts the prognosis of patients after coronary revascularization.

Valor del gated-SPECT para definir el pronóstico tras la revascularización en una población con cardiopatía isquémica / Value of Gated-SPECT in Defining the Post-Revascularization Prognosis of Patients with Ischemic Cardiomyopathy

Introducción y objetivos. Los estudios gated-SPECT, al evaluar simultáneamente perfusión y función ventricular, deberían suministrar importante información pronóstica en cardiopatía isquémica. En una población con cardiopatía isquémica, estudiamos el valor del estudio gated-SPECT antes de la revascularización para predecir su evolución tras ella. Métodos. Se incluyó a 110 pacientes con enfermedad coronaria revascularizada, percutánea (n = 100) o mediante cirugía. Antes de la revascularización, los pacientes se sometieron a un estudio sestamibi gated-SPECT. Tras la revascularización, fueron seguidos durante un período mínimo de 12 meses (tiempo medio, 23,7 meses; máximo, 44 meses). Se analizó la mortalidad y un evento clínico combinado de muerte, infarto no fatal y reingreso por causa cardíaca. Estudiamos el valor pronóstico de variables clínicas y angiográficas y del estudio gatedSPECT. Resultados. Durante el seguimiento se produjeron 14 fallecimientos (6,4 por ciento/año), y en 36 casos se registró evento combinado (16,5 por ciento/año). En el análisis multivariado, la depresión de la fracción de eyección por gatedSPECT (punto de corte, 0,30) fue la única variable relacionada independientemente con la mortalidad (odds ratio [OR] = 4,8; intervalo de confianza [IC] del 95 por ciento, 1,614,6) y el evento combinado (OR = 2,5; IC del 95 por ciento, 1,24,8). El análisis de la supervivencia mostró que los pacientes con fracción de eyección por gated-SPECT 0,30 tuvieron un menor tiempo de supervivencia: 33 (intervalo, 28-38) frente a 42 meses (intervalo, 40-44) (p = 0,002), y libre de eventos: 28 (intervalo, 23-32) frente a 36 meses (intervalo, 33-39) (p = 0,007).Conclusiones. El estudio gated-SPECT, mediante su información sobre la función ventricular izquierda, predice el pronóstico tras la revascularización de los pacientes con enfermedad coronaria (AU)

Simultaneous intracoronary pressure and Doppler guidewires to assess coronary stenosis: if one is enough, are two too much?

We report a potential source of erroneous estimation of stenosis severity by pressure guidewire assessment. Simultaneous introduction of pressure and Doppler guidewires can lead to an overestimation of stenosis pressure gradient in the evaluation of intermediate stenosis.

Capacidad del protocolo de gated-spect reposo/dobutamina para predecir la recuperación contráctil posrevascularización de áreas miocárdicas disinérgicas / The accuracy of the rest/dobutamine gated-SPECT protocol for prediction of contractile recovery after the revascularization of myocardial dysinergic areas

Introducción y objetivo. Los estudios gated-SPECT tienen un campo prometedor en el análisis de la viabilidad miocárdica. Se ha evaluado el rendimiento de un nuevo protocolo de gated-SPECT reposo/dobutamina, basado en el análisis de la reserva contráctil inducida por 10 µg/kg/min de dobutamina, para predecir la recuperación contráctil tras revascularización de zonas miocárdicas disinérgicas. Pacientes y métodos. En 36 pacientes sometidos a revascularización percutánea se seleccionaron 40 territorios vasculares (21 de la arteria descendente anterior y 19 de la coronaria derecha-circunfleja) con depresión severa contráctil basal (método de la línea central aplicado a la ventriculografía de contraste). Mediante cateterismo de control realizado a los 6 meses de la revascularización se comprobó la ausencia de reestenosis angiográfica y se analizó en una nueva ventriculografía la evolución contráctil en los territorios seleccionados, considerándose viables aquellos que presentaron recuperación contráctil. En el estudio gated-SPECT reposo/dobutamina realizado previo a la revascularización se consideró, para cada territorio seleccionado, 'respuesta viable' a la aparición de reserva contráctil inducida por dobutamina (positiva o mejoría [n = 21] y negativa o deterioro [n = 7]), y 'no viable' la ausencia de aquélla (n = 12). Se analizó la evolución de la fracción de eyección en un subgrupo de 27 pacientes con depresión de la función sistólica y revascularización completa. Resultados. El gated-SPECT demostró en el diagnóstico de viabilidad de los territorios vasculares estudiados una sensibilidad de 0,96 (IC del 95 por ciento, 0,78-0,99) y una especificidad de 0,78 (IC del 95 por ciento, 0,48-0,94). La fracción de eyección (mediana [amplitud intercuartil]) mejoró tras la revascularización: 0,42 (0,15) frente a 0,55 (0,22), Z = -3,9, p < 0,001. El diagnóstico de viabilidad por gatedSPECT (p < 0,001) y la extensión de miocardio con depresión severa contráctil (p = 0,04) predijeron independientemente la mejoría de la fracción de eyección tras revascularización. Conclusión: El análisis de la reserva contráctil mediante el protocolo gated-SPECT reposo/dobutamina posee un buen rendimiento para diagnosticar la viabilidad de territorios vasculares con alteración contráctil basal y predice de forma independiente la mejoría de la fracción de eyección posterior a la revascularización (AU)