microRNA-21 e fibrosi miocardica nel remodeling da Stenosi Aortica: uno studio mediante Strain bidimensionale ultrasonoro

La Stenosi Valvolare Aortica (SVA) degenerativa rappresenta la più comune valvulopatia nativa nei paesi occidentali e la prima per cui vengano oggi poste indicazioni ad intervento. La progressione dalle forme di ostruzione lieve a severa è spesso graduale e si accompagna al lento instaurarsi di alterazioni fisiopatologiche a livello ventricolare sinistro dovute al sovraccarico pressorio (ipertrofia concentrica e progressiva fibrosi tissutale). Attualmente, le indicazioni ad intervento di sostituzione valvolare (AVR, Aortic Valve Replacement) sono poste all'insorgere di sintomi tipici, altrimenti, al manifestarsi di una riduzione della frazione di eiezione (FE<50%); tuttavia, entrambi questi approcci possono essere inappropriati, poiché si associano ad alterazioni della contrattilità e del tessuto miocardico a volte non reversibili dopo intervento. La frazione di eiezione è un indicatore poco sensibile delle alterazioni precoci della contrattilità e della funzione longitudinale. Quest’ultima, infatti, viene ad essere compromessa per prima nel processo di rimodellamento. Le moderne metodiche di imaging ecocardiografico (Speckle Tracking Imaging, STI) consentono oggi una valutazione più accurata della meccanica cardiaca stimando in maniera rapida, non invasiva, riproducibile, multi-direzionale ed angolo-indipendente, la deformazione miocardica e le alterazioni tissutali che caratterizzano questi pazienti sin dalle fasi precoci. Inoltre, nuovi marcatori bioumorali, implicati nel processo fisiopatologico di sovraccarico pressorio e fibrosi tissutale alla base della stenosi aortica, come i microRNA (miRNA), possono avere un ruolo aggiuntivo nella stratificazione dei pazienti. Nel presente studio, 36 pazienti affetti da Stenosi Valvolare Aortica severa sintomatica e frazione di eiezione preservata (FE>50%), sono stati sottoposti a valutazione clinica (visita, ECG, score di rischio cardiochirurgico EUROSCORE), ecocardiografica (includente Tissue Doppler Imaging, TDI e STI) e laboratoristica (BNP, Troponin T hs, miRNA-21). In particolare è stata effettuata una valutazione del Global Longitudinal Strain (GLS), Global Longitudinal Strain rate Sistolico (GLSrS) e Proto-diastolico (GLSrE), Septal Longitudinal Strain (SLs), Septal Longitudinal Strain rate Sistolico (SrSs) e Strain rate Proto-diastolico (SrEs). 28 di questi soggetti sono stati sottoposti ad intervento di sostituzione valvolare aortica chirurgica (AVR) e 23 a concomitante biopsia del setto interventricolare basale. Sui campioni di tessuto disponibili (20) è stata effettuata una stima della percentuale di fibrosi tissutale sostitutiva (sezione e colorazione del campione con Ematossilina/Eosina e Tricromica di Masson). E’ stata inoltre effettuata un’analisi dei livelli di espressione di miRNA-21 plasmatico in 30 dei pazienti. Lo studio ecocardiografico ha rilevato disfunzione diastolica e tendenziale aumento delle pressioni di riempimento, una netta compromissione della funzione longitudinale valutata tramite Mitral Annular Plane Systolic Excursion (MAPSE), TDI e GLS. Lo studio tissutale (23 pazienti) ha inoltre individuato una correlazione inversa tra GLS, SrSs e SrEs longitudinale e % di fibrosi tissutale. Inoltre i parametri di deformazione miocardica e la fibrosi tissutale hanno dimostrato di possedere, a differenza degli altri indici di funzione sistolica, una capacità di discriminare accuratamente pazienti con classe funzionale avanzata e di correlare con i valori di BNP. I valori plasmatici di miRNA-21 hanno evidenziato una buona correlazione con quelli della massa ventricolare sinistra indicizzata (LVMi); inoltre lo studio ha evidenziato una diretta correlazione tra miRNA-21 plasmatico e fibrosi miocardica (MF), mentre indiretta è la correlazione con SLs. Le principali conclusioni che possiamo trarre da questo studio sono essenzialmente tre. I Pazienti con SVA severa mostrano alterazioni della deformazione globale e regionale miocardica, che riflette un sovraccarico pressorio e remodeling geometrico. Queste anomalie sono principalmente correlate con la MF, la quale sopraggiunge in uno stadio precoce di SVA con preservata FE. In seconda istanza, il livello d’espressione di miRNA-21 documenta un significativo ruolo nella fisiopatologia della SVA, essenzialmente per fibrogenesi. Infine, ì livelli circolanti di miRNA-21 (biomarker) sono aumentati nei pazienti con SVA severa, ma con un grado di espressione differente in pazienti che presentano o meno fibrosi miocardica ( del 10%). In conclusione, l’utilizzo di parametri bioumorali e metodiche strumentali più oggettive ed accurate per la valutazione della meccanica cardiaca, può consentire un migliore approccio terapeutico al trattamento dei pazienti con Stenosi Valvolare Aortica, permettendo di individuare precocemente alterazioni ultra-strutturali e deficit contrattili difficilmente reversibili anche dopo l’intervento

Speckle-Tracking Imaging, Principles and Clinical Applications: A Review for Clinical Cardiologists

Evaluation of myocardial mechanics, although complex, has now entered the clinical arena, thanks to the introduction of bedside imaging techniques, such as speckle-tracking echocardiography

Classes of Colors and Timbres: A Clustering Approach

Similarities between different sensory dimensions can be addressed considering common ``movements'' as causes, and emotional responses as effects. An imaginary movement toward the ``dark'' produces ``dark sounds'' and ``dark colors,'' or, toward the ``bright,'' ``brighter colors'' and ``brighter sounds.''Following this line of research, we draw upon the confluence of mathematics and cognition, extending to colors and timbres the gestural similarity conjecture, a development of the mathematical theory of musical gestures.Visual ``gestures'' are seen here as paths in the space of colors, compared with paths in the space of orchestral timbres.We present an approach based on clustering algorithm to evaluate the association between color bands and orchestral timbres.The analysis is based on 8 indicators which represent and describe participants' background and associations to be tested.  The indicators include socio-demographic information and color class options from the color space, to associate with each given timbre class.We clustered responders into homogeneous groups where the within-group-object dissimilarity is minimized and the between-group-object dissimilarity is maximized. The partitions are obtained with k-modes. While participants' background does have an influence in their answers, the overall behaviors confirms the existence of different space regions for different timbres, supporting our hypothesis of perceived similarities similarities between color and timbre classes. In fact, the cluster analysis confirms identifiable blocks.Our pioneering study on a small dataset may open the way toward a future and deeper comprehension of complex color-timbre perceived connections

Classes of Colors and Timbres: A Clustering Approach

Similarities between different sensory dimensions can be addressed considering common ``movements'' as causes, and emotional responses as effects. An imaginary movement toward the ``dark'' produces ``dark sounds'' and ``dark colors,'' or, toward the ``bright,'' ``brighter colors'' and ``brighter sounds.''Following this line of research, we draw upon the confluence of mathematics and cognition, extending to colors and timbres the gestural similarity conjecture, a development of the mathematical theory of musical gestures.Visual ``gestures'' are seen here as paths in the space of colors, compared with paths in the space of orchestral timbres.We present an approach based on clustering algorithm to evaluate the association between color bands and orchestral timbres.The analysis is based on 8 indicators which represent and describe participants' background and associations to be tested.  The indicators include socio-demographic information and color class options from the color space, to associate with each given timbre class.We clustered responders into homogeneous groups where the within-group-object dissimilarity is minimized and the between-group-object dissimilarity is maximized. The partitions are obtained with k-modes. While participants' background does have an influence in their answers, the overall behaviors confirms the existence of different space regions for different timbres, supporting our hypothesis of perceived similarities similarities between color and timbre classes. In fact, the cluster analysis confirms identifiable blocks.Our pioneering study on a small dataset may open the way toward a future and deeper comprehension of complex color-timbre perceived connections

Radiation Therapy for Non-Small Cell Lung Cancer in the Twenty-First Century

Lung cancer is the biggest oncologic problem for global health, as it is the most deadly and prevalent pathology after skin cancer. Two million patients are diagnosed every year, and around 80% of them die due to the disease. Radiotherapy has been practiced for decades to treat these patients, but recently, there has been important advances on this treatment on early stages (I and II), as stereotactic radiation therapy is becoming crucial. There has also been an increase on the importance of this treatment on more advanced stages (III), since intensity-modulated radiation therapy has achieved the reduction of undesirable side effects. The performance of stereotactic radiation at metastasis stages on patients with oligometastasis has accomplished great results. Likewise, hypofractionated treatments on polymetastatic patients have increased their quality of life

Psoriasis induced by first‑line pembrolizumab in metastatic non‑small cell lung cancer: a case report

: Therapeutic options for non-small cell lung cancer (NSCLC) have changed with the introduction of immune checkpoint inhibitors. Immunotherapy is generally well tolerated, but can also be associated with severe adverse events, such as the development of new autoimmune diseases. In patients without a history of autoimmune diseases, psoriasis caused by immunotherapy treatment is rarely described in the literature. The present study describes the case of a 68-year-old man with metastatic NSCLC that started chemoimmunotherapy with carboplatin plus pemetrexed plus pembrolizumab. After two cycles of therapy, the patient developed a G3 maculopapular rash. Biopsy confirmed psoriasis and pembrolizumab treatment was discontinued. At the last follow up, the patient was still on maintenance therapy with pemetrexed alone, which is well tolerated. Psoriasis has rarely been reported as an immune-related adverse event. Although the patient had to stop the immunotherapy treatment, the patient is still exhibiting a response to it. Notably, it has previously been described how skin toxicities are associated with a better outcome. Other studies need to be conducted to identify the risk and predictive factors associated with severe immune adverse events and objective response

Social disconnectedness, loneliness, and mental health among adolescents in Danish high schools : a nationwide cross-sectional study

Background: Previous research has suggested that social disconnectedness experienced at school is linked to mental health problems, however, more research is needed to investigate (1) whether the accumulation of various types of social disconnectedness is associated with risk for mental health problems, and (2) whether loneliness is a mechanism that explains these associations. Methods: Using data from the Danish National Youth Study 2019 (UNG19), nation-wide cross-sectional data from 29,086 high school students in Denmark were analyzed to assess associations between social disconnectedness experienced at school (lack of classmate support, lack of teacher support, lack of class social cohesion, and not being part of the school community) and various mental health outcomes, as well as the mediating role of loneliness for each type of disconnectedness. Multilevel regression analyses were conducted to assess the associations. Results: Descriptive analyses suggest that 27.5% of Danish high school students experience at least one type of social disconnectedness at school. Each type of social disconnectedness was positively associated with mental health problems (depression symptoms, anxiety symptoms, stress, sleep problems, suicidal ideation, non-suicidal self-injury, eating disorder, body dissatisfaction, and low self-esteem) and negatively associated with mental well-being. In all cases, loneliness significantly mediated the associations. We found a clear dose-response pattern, where each addition in types of social disconnectedness was associated with (1) stronger negative coefficients with mental well-being and (2) stronger positive coefficients with mental health problems. Conclusion: Our results add to a large evidence-base suggesting that mental health problems among adolescents may be prevented by promoting social connectedness at school. More specifically, fostering social connectedness at school may prevent loneliness, which in turn may promote mental well-being and prevent mental health problems during the developmental stages of adolescence. It is important to note that focusing on single indicators of school social connectedness/disconnectedness would appear to be insufficient. Implications for practices within school settings to enhance social connectedness are discussed

La eco-epidemiología retrospectiva como herramienta aplicada a la vigilancia de la leishmaniasis en Misiones, Argentina, 1920-2014

Se presenta una metodología analítica retrospectiva, basada en el marco teórico de la ecoepidemiología, anclada en una escala espacial subnacional. Esta metodología, aplicada aquí a la caracterización de escenarios de transmisión de la leishmaniasis en la provincia argentina de Misiones —fronteriza con Brasil y Paraguay— permitió fundamentar recomendaciones de vigilancia y control apropiadas a dicha escala. Se realizó una búsqueda exhaustiva de la literatura sobre leishmaniasis en esa provincia y se determinaron tres escenarios de transmisión de leishmaniasis cutánea (LC) y visceral (LV), correspondientes a tres períodos: 1920-1997, en el que se constató la transmisión de LC, dispersa en el tiempo y el espacio; 1998-2005, en el que hubo brotes focales de LC; y 2006-2014 en el que, además, se registraron brotes y se documentó la dispersión geográfica de la LV. Para caracterizar los escenarios de riesgo y los procesos antrópicos que los producen, los resultados se sintetizaron e integraron en el contexto socio-histórico y bio-ecológico de cada período analizado. Se fundamentan recomendaciones de vigilancia y control en el territorio estudiado, entre ellas, establecer una vigilancia activa para monitorear posibles tendencias al incremento de la circulación parasitaria y vectorial y, ante la aparición de un foco, realizar estudios para verificar la transmisión autóctona y la intensidad del evento. Además, se debe establecer la obligación legal de tomar medidas adicionales de control por los responsables de los proyectos que impliquen modificación ambiental, como la realización de estudios de evaluación del riesgo de transmisión, y acciones de mitigación del riesgo, detección temprana y tratamiento oportuno de los casos.Fil: Salomón, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Ministerio de Salud. Instituto Nacional de Medicina Tropical; ArgentinaFil: Mastrangelo, Andrea Veronica. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Santini, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; ArgentinaFil: Liotta, Domingo Javier. Ministerio de Salud. Instituto Nacional de Medicina Tropical; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Yadón, Zaida Estela. Organización Panamericana de la Salud; Brasi

Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC)

Background and aim: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. Materials and Methods: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. Results: Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128). Conclusions: Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC. © 2011 Bentham Science Publishers Ltd