Single-Center Experience with Trabectedin for the Treatment of Non-L-sarcomas.

INTRODUCTION: The effectiveness of trabectedin for the treatment of leiomyosarcoma and liposarcoma (commonly referred to as L-sarcomas) has been widely evidenced in clinical trials and real-world studies. Nevertheless, available literature on non-L-sarcomas is less abundant. The objective of the present study is to evaluate the effectiveness and safety of trabectedin in a cohort of patients with non-L-sarcomas in the real-world setting. METHODS: This retrospective, observational study included 34 patients who received trabectedin in the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) between October 2013 and July 2020. RESULTS: The most frequent histologic subtypes were undifferentiated spindle cell/pleomorphic sarcoma (n = 11, 32.4%), synovial sarcoma (n = 6, 17.7%), myxofibrosarcoma (n = 5, 14.7%), and malignant peripheral nerve sheath tumor (n = 4, 11.8%). The mean number of cycles with trabectedin was 5.5 (range 2-28). Three patients achieved partial response (8.8%) and eight patients showed stable disease (23.5%). The objective response rate and disease control rate were 8.8% (95% confidence interval (CI), 95% CI 1.9-23.7) and 32.4% (95% CI 17.4-50.5), respectively. Overall, progression-free survival was 2.9 months (95% CI 2.1-3.4). The overall survival was 7.3 months (95% CI 4.7-12.8). The most common trabectedin-related grade 3 adverse events were observed in 10 patients (26.5%), mostly being neutropenia (14.7%) and elevated transaminases (5.9%), whereas one patient (2.9%) reported grade 4 febrile neutropenia that required hospitalization. CONCLUSIONS: The findings of this real-life study consistently support that trabectedin is an effective and safe option for the treatment of patients with non-L-sarcoma after failure of anthracyclines and ifosfamide, or in patients who are unsuited to receive these agents.

Effect of Continuous Administration of Enalapril Maleate on the Oocyte Quality and In Vitro Production of Parthenote Embryos in Nulliparous and Multiparous Goats Undergoing Serial Laparoscopic Ovum Pick-Up.

The aim of this work was to determine the effect of enalapril maleate administration, during oocyte recovery by serial laparoscopic ovum pick-up (LOPU), on the ovarian response and in vitro embryo production (IVP). Twenty cross-bred goats were allocated equally into two groups: Nulliparous and Multiparous. In each group, five animals were selected to receive daily doses of enalapril maleate during the hormonal protocol. Estrus was synchronized by a PGF2α analog, followed 48 h later by insertion of an intravaginal device with progesterone. Forty-eight hours after, a single dose of FSH/eCG was administered. The FSH/eCG doses were repeated three times, on every four day. Oocytes were recovered by LOPU 24 h after each FSH/eCG dose. Viable oocytes were matured in vitro, to be parthenogenetically activated and cultured for 72 h to the cleavage stage. The drug treatment increased the proportion of total follicles observed at LOPU (p < 0.01) in multiparous goats. In both parity groups, enalapril administration had no effect on the proportion or quality of oocytes recovered. Furthermore, the number of embryos cleaved was similar between the groups. Thus, enalapril maleate affected the ovarian response in multiparous animals only and had no effect on the oocyte quality or IVP.

Seroprevalencia de la Leishmaniasis Visceral Canina mediante Elisa con rK39 en Focos Endémicos de Venezuela / Seroprevalence of Canine Visceral Leishmaniasis by rK39-ELISA in Endemic Foci in Venezuela

En el presente trabajo se presenta la seroprevalencia de la leishmaniasis visceral canina (LVC), zoonosis causada por Leishmania infantum/chagasi. Se realizaron pruebas serológicas y examen clínico a 15.822 perros de 13 entidades federales endémicas para la leishmaniasis visceral en Venezuela, en el periodo 2004-2012. Los sueros fueron analizados mediante ELISA con el antígeno recombinante rK39. Los resultados muestran que 14,8% de la población de caninos son positivos para LV. Los estados Lara (19%) y Guárico (18%) mostraron una mayor prevalencia de la enfermedad. Sin embargo, para los años 2010-2012, la prevalencia de la LVC para las entidades federales como Anzoátegui, Aragua, Carabobo, Cojedes, Nueva Esparta y Sucre se mantuvieron entre un 3% y un 31%. Los caninos seropositivos (67,1% machos y 32,9% hembras) tenían edades promedio de 4,8±2,9 años. El 81% de los caninos seropositivos encontrados en estas zonas, no presentó signos clínicos característicos de LVC, mientras que la clínica presentada por el resto fueron ulceraciones cutáneas (8,5%), alopecia (9,4%) y onicogrifosis (19,2%). Este reporte muestra la distribución geográfica (tanto en zonas rurales como urbanas) y características clínicas más resaltantes de perros parasitados en las diferentes regiones endémicas del país, con el fin de tomar medidas estratégicas que fortalezcan los programas de control y prevención de esta zoonosis problema de salud pública.

This study discloses the seroprevalence of canine visceral leishmaniasis (CVL), a zoonotic disease caused by Leishmania infantum/chagasi. In this study, serological tests and clinical examinations were performed in 15,822 dogs from 13 federal entities endemic for visceral leishmaniasis in Venezuela, during the period 2004-2012. Serum samples were analysed by ELISA against the recombinant antigen rK39. Results demonstrated a prevalence of 14.8% of positive dogs for VL. Lara (19%) and Guárico (18%) states showed the highest seroprevalence of the disease. However, for the years 2010-2012, the prevalence of CVL for federal entities as Anzoátegui, Aragua, Carabobo, Cojedes, Nueva Esparta, and Sucre remained between 3% and 31%. The seropositive canines (67.1% males and 32.9% females) average 4.8±2.9 years of age and 81% of the dogs found in these endemic areas did not show clinical signs characteristic of LVC, while clinical symptoms presented by the rest were skin ulceration (8.5%), alopecia (9.4%) and onychogryphosis (19.2%). This report demonstrates the geographical distribution (both rural and urban) and most striking clinical features of parasitized dogs in different endemic regions of the country, in order to take strategic actions to strengthen the control and prevention programs of this public health problem.

Effect of intrauterine HIV-1 exposure on the frequency and function of uninfected newborns' dendritic cells.

Immaturity of the neonatal immune system is considered an underlying factor for enhanced severity of infections in newborns. Functional defects of neonatal antigen-presenting cells lead to defective T-cell responses. T cells from uninfected neonates exposed in utero to HIV-1 (EU) exhibit phenotypic and functional alterations; however, the function of their circulating dendritic cells (DCs) has not been characterized. We hypothesized that an HIV-1-infected maternal environment may influence the infants' DC number, phenotype and function. EU exhibited a higher percentage of myeloid DCs (mDCs) than unexposed neonates, although this frequency remained lower than that observed in adults. Plasmacytoid DC (pDC) frequencies were similar in all groups, although both groups of infants tended to have lower frequencies than adults. After LPS stimulation, mDCs from EU up-regulated CD80, CD86 and B7-H1, whereas mDCs from unexposed infants upregulated B7-H1, but not CD80/CD86, and adult mDCs up-regulated mainly CD80 and CD86. IFN-alpha production was similar in all groups, indicating a normal pDC function. Therefore, in utero exposure to HIV-1 induces quantitative and qualitative changes in neonatal DCs, particularly in mDCs, which might be associated with alterations observed in T cells from these EU.

Células NK: generalidades y papel durante la infección por el virus de la inmunodeficiencia humana tipo 1 (VIH-1) / NK cels: characteristics and role during the infection by type-1 human inmunodeficiency virus (HIV-1)

Las células NK exhiben actividad espontánea contra células tumorales o células infectadas, particularmente por virus. Ellas se caracterizan por la expresión de las moléculas CD16 y CD56, y se subdividen en dos poblaciones, CD16Low/CD56Hi y CD16Hi/CD56Low, que difieren en las citoquinas que producen y en la capacidad citotóxica. La activación de las células NK está regulada por la expresión de receptores inhibidores y activadores que interactúan con diferentes ligandos de las células blanco. La actividad efectora de estas células incluye la lisis de las células blanco por diferentes mecanismos y la producción de citoquinas; las células NK participan por medio de estos factores solubles en diversos procesos fisiológicos, como la hematopoyesis y la regulación de otras células del sistema inmune. Durante la infección por el VIH-1, las células NK ayudan al control de la replicación viral tanto por mecanismos citotóxicos como por la producción de citoquinas, particularmente beta-quimoquinas. Sin embargo, el VIH-1 ha desarrollado mecanismos para evadir la respuesta antiviral mediada por las células NK. Adicionalmente, esta infección induce anormalidades cuantitativas y funcionales en estas células que puedenpresentarse muy temprano en la evolución de la enfermedad y que hacen parte de la inmunosupresión severa característica del SIDA.

Antibodies to lens crystallins after endocapsular cataract surgery

Levels of serum antibodies against lens alpha, beta H and beta L crystallins were determined in 15 patients before and after endocapsular cataract extraction. The most abundant antibody at the time of surgery was anti-beta L, followed by anti-beta H and anti-alpha. An increase in the basal levels of these antibodies was seen after surgery in 93 percent of the cases. Relative increase was highest for anti-alpha, followed by anti-beta H and anti-beta L. There were individual variations both in the shape of the time-dependent antibody response after surgery and in the relative intensity of the response to the different antigens. The endocapsular technique therefore leads to the release of crystallins into the anterior chamber in sufficient amounts to provoke in many patients a humoral immune response