Cancer Vaccines: From the State of the Art to the Most Promising Frontiers in the Treatment of Colorectal Cancer.

Colorectal cancer represents 10% of all new cancer cases each year and accounts for almost 10% of all cancer deaths. According to the WHO, by 2040 there will be a 60% increase in colorectal cancer cases. These data highlight the need to explore new therapeutic strategies. Classical interventions include surgical resection, chemotherapy and radiotherapy, which are invasive strategies that have many side effects on the patients and greatly affect their quality of life. A great advance in the treatment of this cancer type, as well as of all the others, could be the development of a vaccination strategy preventing the onset, the progression or the relapse of the pathology. In this review, we summarize the main vaccination strategies that are being studied for the treatment of colorectal cancer (CRC) and finally explore the possibility of using B-cells for the development of a new type of vaccine.

3D Reconstruction of the Clarified Rat Hindbrain Choroid Plexus.

The choroid plexus (CP) acts as a regulated gate between blood and cerebrospinal fluid (CSF). Despite its simple histology (a monostratified cuboidal epithelium overlying a vascularized stroma), this organ has remarkably complex functions several of which involve local interaction with cells located around ventricle walls. Our knowledge of CP structural organization is mainly derived from resin casts, which capture the overall features but only allow reconstruction of the vascular pattern surface, unrelated to the overlying epithelium and only loosely related to ventricular location. Recently, CP single cell atlases are starting to emerge, providing insight on local heterogeneities and interactions. So far, however, few studies have described CP spatial organization at the mesoscale level, because of its fragile nature and deep location within the brain. Here, using an iDISCO-based clearing approach and light-sheet microscopy, we have reconstructed the normal rat hindbrain CP (hCP) macro- and microstructure, using markers for epithelium, arteries, microvasculature, and macrophages, and noted its association with 4th ventricle-related neurovascular structures. The hCP is organized in domains associated to a main vessel (fronds) which carry a variable number of villi; the latter are enclosed by epithelium and may be flat (leaf-like) or rolled up to variable extent. Arteries feeding the hCP emerge from the cerebellar surface, and branch into straight arterioles terminating as small capillary anastomotic networks, which run within a single villus and terminate attaching multiple times to a large tortuous capillary (LTC) which ends into a vein. Venous outflow mostly follows arterial pathways, except for the lateral horizontal segment (LHS) and the caudal sagittal segment. The structure of fronds and villi is related to the microvascular pattern at the hCP surface: when LTCs predominate, leaflike villi are more evident and bulge from the surface; different, corkscrew-like villi are observed in association to arterioles reaching close to the CP surface with spiraling capillaries surrounding them. Both leaf-like and corkscrew-like villi may reach the 4th ventricle floor, making contact points at their tip, where no gap is seen between CP epithelium and ependyma. Contacts usually involve several adjacent villi and may harbor epiplexus macrophages. At the junction between medial (MHS) and lateral (LHS) horizontal segment, arterial supply is connected to the temporal bone subarcuate fossa, and venous outflow drains to a ventral vein which exits through the cochlear nuclei at the Luschka foramen. These vascular connections stabilize the hCP overall structure within the 4th ventricle but make MHS-LHS joint particularly fragile and very easily damaged when removing the brain from the skull. Even in damaged samples, however, CP fronds (or isolated villi) often remain strongly attached to the dorsal cochlear nucleus (DCN) surface; in these fronds, contacts are still present and connecting "bridges" may be seen, suggesting the presence of real molecular contacts rather than mere appositions.

La región sudeste del Gran Buenos Aires frente a la pandemia Evaluación de la ampliación del sistema de salud en el marco de la COVID 19 / The Southeastern region of the Buenos Aires Province metropolitan area in the face of the pandemic: evaluation of the expansion of the health system in the framework of COVID-19

INTRODUCCIÓN: La región sudeste del Gran Buenos Aires (GBA) reformuló el sistema público de salud por la pandemia de COVID19. Entre las medidas que se tomaron, está la ampliación del número de camas mediante la construcción y puesta en marcha de tres hospitales. OBJETIVO: Evaluar el impacto de la ampliación del número de camas en los resultados de internación de los pacientes asistidos por los efectores públicos de salud durante el período de estudio (8 de abril de 2020 al 11 de septiembre de 2020). MÉTODOS: Estudio descriptivo a partir de información registrada en el Tablero COVID-19, software de gestión desarrollado por el equipo del Instituto del Cálculo de la Universidad de Buenos Aires, en el que se obtienen datos de cada paciente internado en la red de efectores de salud; se evalúan los resultados del efecto del aumento de la capacidad instalada. RESULTADOS: Se registraron 2 306 pacientes internados, de los cuales 266 (11,54%) requirieron internación en unidad de cuidados intensivos (UCO), 1 786 (77,4%) en cuidados intermedios y 254 (11%) pacientes en sala general. La media de edad fue de 50,63 y los pacientes de sexo masculino representaron el 55,5% del total. Se produjeron 253 muertes (10,97%), de las cuales el 64% fueron hombres. El 58,3% del total tenían enfermedades preexistentes, estos tienen un riesgo 90% más alto que quienes no las tenían. El promedio total de ocupación de camas en UCI fue del 40,7%, mientras que el de ocupación en cuidados intermedios fue de 61,5%. Sin los hospitales nuevos, 169 pacientes (9,46%) no hubieran tenido camas en cuidados intermedios y 31 pacientes (11,6%) no hubieran tenido cama en la UCI. DISCUSIÓN: El sistema de salud de la región sudeste del GBA se preparó de manera adecuada gracias a la ampliación del número de camas de internación.

Efecto del clampeo demorado del cordón umbilical en la ferritina sérica a los seis meses de vida. Estudio clínico controlado aleatorizado / The effect ofearly and delayed umbilical cord clamping onferritin levels in term infants at six months oflife. A randomized, controlled trial

Introducción. El clampeo demorado del cordón umbilical aumentaría el depósito de hierro en lactantes. Para comprobar esta hipótesis medimos la ferritina sérica a los seis meses de vida en niños nacidos a término, participantes en un estudio controlado aleatorizado que evaluó el efecto del tiempo de clampeo del cordón en el hematócrito venoso y la evolución neonatal. Métodos. De 276 neonatos incluidos en el estudio original, 255 (92,4%) fueron seguidos seis meses, 86 tuvieron clampeo temprano, 83 al minuto y 83 al tercer minuto. La variable principal de resultado fue la concentración de ferritina sérica a los seis meses. Resultados. Las características de los grupos de madres y niños fueron similares. La ferritina fue significativamente más alta en los niños con clampeo al tercer minuto (33,2 μg/L) que en los de clampeo temprano (20,9 μg/L) (diferencia de medias geométrica: 1,6; IC 95%: 1,2-2,1). No hubo diferencia significativa entre clampeo al minuto (25,5 μg/L) y clampeo temprano. Tampoco hubo diferencia en los valores medios de hemoglobina, entre los grupos temprano [10,6 g/dl (DE 1,11)], al minuto [10,8 g/dl (DE 0,86)] y tres minutos [10,7 g/dl (DE 0,97)], respectivamente. La prevalencia de anemia ferropénica fue tres veces mayor en niños con clampeo temprano (7%) en comparación con los del tercer minuto (2,4%) (diferencias no significativas; RR: 0,30; IC 95%: 0,10-1,60). Conclusión. En niños nacidos a término, el clampeo del cordón umbilical a los tres minutos del nacimiento aumentó significativamente las concentraciones de ferritina a los seis meses de edad. No hubo diferencias significativas en los niveles de hemoglobina.

Background. Delayed umbilical cord clamping could increase iron stores and prevent iron deficieney in infants. To test this hypothesis we measured serum ferritin and hemoglobin levels at six months of age in term infants who had participated in a randomized controlled trial, assessing the effect of cord clamping timing on neonatal hematocrit values and clinical outcome. Main outcome measure. Serum ferritin level at six months of age. Methods. Out of the 276 mothers and their infants that participated in the initial study, 255 (92.4%) were followed up to six months and included in this study. Of these, 86 had their cords clamped within the first 15 seconds (early clamping), 83 at one minute, and 83 at three minutes. The pediatricians in charge of the evaluations during the follow-up period and personnel in charge of the biochemical tests were blinded to the assignment group. In all but 3 infants the ferritin levels and hemoglobin levels were measured at six months of age. Results. Mothers and infants in the three groups had similar baseline characteristics. Serum ferritin levels were significantly higher in the infants of the three minutes group than in the infants of the early group: 33.2 μg/L vs. 20.9 ug/L(geometric mean ratio: 1.6;95%CI: 1.2 to 2.11) but no difference was observed in one minute group (25.5 μg/L) vs. early group. There were no significant differences inmeanhemoglobin values, 10.6 g/dl (SD 1,1); 10.8 g/dl (SD 0.9) and 10.7 g/dl (SD 1.0) between groups early, one minute, and three minutes, respectively. Although there were no significant differences between groups, the prevalence of iron deficiency anemia (hemoglobin < 10.5 g/dl and ferritin < 9 μg/L) was 3 times more frequent in early clampling group (7.2%) than in three minutes group (2.4%) (RR: 0.30; IC 95%: 0.10-1.60). Conclusions. Delayed umbilical cord clamping at three minutes significantly increases serum ferritin levels in infants at 6 months of age. No significant differences were found between groups in mean hemoglobin levels.

[The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life: a randomized, controlled trial]. / Efecto del clampeo demorado del cordón umbilical en la ferritina sérica a los seis meses de vida: Estudio clínico controlado aleatorizado.

BACKGROUND: Delayed umbilical cord clamping could increase iron stores and prevent iron deficiency in infants. To test this hypothesis we measured serum ferritin and hemoglobin levels at six months of age in term infants who had participated in a randomized controlled trial, assessing the effect of cord clamping timing on neonatal hematocrit values and clinical outcome. Main outcome measure. Serum ferritin level at six months of age. METHODS: Out of the 276 mothers and their infants that participated in the initial study, 255 (92.4%) were followed up to six months and included in this study. Of these, 86 had their cords clamped within the first 15 seconds (early clamping), 83 at one minute, and 83 at three minutes. The pediatricians in charge of the evaluations during the follow-up period and personnel in charge of the biochemical tests were blinded to the assignment group. In all but 3 infants the ferritin levels and hemoglobin levels were measured at six months of age. RESULTS: Mothers and infants in the three groups had similar baseline characteristics. Serum ferritin levels were significantly higher in the infants of the three minutes group than in the infants of the early group: 33.2 microg/L vs. 20.9 microg/L (geometric mean ratio: 1.6; 95% CI: 1.2 to 2.11) but no difference was observed in one minute group (25.5 microg/L) vs. early group. There were no significant differences in mean hemoglobin values, 10.6 g/dl (SD 1,1); 10.8 g/dl (SD 0.9) and 10.7 g/dl (SD 1.0) between groups early, one minute, and three minutes, respectively. Although there were no significant differences between groups, the prevalence of iron deficiency anemia (hemoglobin < 10.5 g/dl and ferritin < 9 microg/L) was 3 times more frequent in early clampling group (7.2%) than in three minutes group (2.4%) (RR: 0.30; IC 95%: 0.10-1.60). CONCLUSIONS: Delayed umbilical cord clamping at three minutes significantly increases serum ferritin levels in infants at 6 months of age. No significant differences were found between groups in mean hemoglobin levels.

Efecto del clampeo demorado del cordón umbilical en la ferritina sérica a los seis meses de vida. Estudio clínico controlado aleatorizado / The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life. A randomized, controlled trial

Introducción. El clampeo demorado del cordón umbilical aumentaría el depósito de hierro en lactantes.Para comprobar esta hipótesis medimos la ferritina sérica a los seis meses de vida en niños nacidos a término, participantes en un estudio controlado aleatorizado que evaluó el efecto del tiempo de clampeo del cordón en el hematócrito venoso y la evolución neonatal.Métodos. De 276 neonatos incluidos en el estudio original, 255 (92,4 por ciento) fueron seguidos seis meses, 86 tuvieron clampeo temprano, 83 al minuto y 83 al tercer minuto. La variable principal de resultado fue la concentración de ferritina sérica a los seis meses. Resultados. Las características de los grupos de madres y niños fueron similares. La ferritina fue significativamente más alta en los niños con clampeo al tercer minuto (33,2 μg/L) que en los de clampeo temprano (20,9 μg/L) (diferencia de medias geométrica: 1,6; IC 95 por ciento: 1,2-2,1). No hubo diferencia significativa entre clampeo al minuto(25,5 μg/L) y clampeo temprano. Tampoco hubo diferencia en los valores medios de hemoglobina,entre los grupos temprano [10,6 g/dl (DE 1,11)], al minuto [10,8 g/dl (DE 0,86)] y tres minutos [10,7 g/dl (DE 0,97)], respectivamente.La prevalencia de anemia ferropénica fue tres veces mayor en niños con clampeo temprano(7 por ciento) en comparación con los del tercer minuto (2,4 por ciento) (diferencias no significativas; RR: 0,30;IC 95 por ciento: 0,10-1,60).Conclusión. En niños nacidos a término, el clampeo del cordón umbilical a los tres minutos del nacimiento aumentó significativamente las concentracionesde ferritina a los seis meses de edad.No hubo diferencias significativas en los niveles de hemoglobina.

Efecto del clampeo demorado del cordón umbilical en la ferritina sérica a los seis meses de vida. Estudio clínico controlado aleatorizado / The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life. A randomized, controlled trial

Introducción. El clampeo demorado del cordón umbilical aumentaría el depósito de hierro en lactantes.Para comprobar esta hipótesis medimos la ferritina sérica a los seis meses de vida en niños nacidos a término, participantes en un estudio controlado aleatorizado que evaluó el efecto del tiempo de clampeo del cordón en el hematócrito venoso y la evolución neonatal.Métodos. De 276 neonatos incluidos en el estudio original, 255 (92,4 por ciento) fueron seguidos seis meses, 86 tuvieron clampeo temprano, 83 al minuto y 83 al tercer minuto. La variable principal de resultado fue la concentración de ferritina sérica a los seis meses. Resultados. Las características de los grupos de madres y niños fueron similares. La ferritina fue significativamente más alta en los niños con clampeo al tercer minuto (33,2 μg/L) que en los de clampeo temprano (20,9 μg/L) (diferencia de medias geométrica: 1,6; IC 95 por ciento: 1,2-2,1). No hubo diferencia significativa entre clampeo al minuto(25,5 μg/L) y clampeo temprano. Tampoco hubo diferencia en los valores medios de hemoglobina,entre los grupos temprano [10,6 g/dl (DE 1,11)], al minuto [10,8 g/dl (DE 0,86)] y tres minutos [10,7 g/dl (DE 0,97)], respectivamente.La prevalencia de anemia ferropénica fue tres veces mayor en niños con clampeo temprano(7 por ciento) en comparación con los del tercer minuto (2,4 por ciento) (diferencias no significativas; RR: 0,30;IC 95 por ciento: 0,10-1,60).Conclusión. En niños nacidos a término, el clampeo del cordón umbilical a los tres minutos del nacimiento aumentó significativamente las concentracionesde ferritina a los seis meses de edad.No hubo diferencias significativas en los niveles de hemoglobina.(AU)

The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term: a randomized, controlled trial.

BACKGROUND: The umbilical cord is usually clamped immediately after birth. There is no sound evidence to support this approach, which might deprive the newborn of some benefits such as an increase in iron storage. OBJECTIVES: We sought to determine the effect of timing of cord clamping on neonatal venous hematocrit and clinical outcome in term newborns and maternal postpartum hemorrhage. METHODS: This was a randomized, controlled trial performed in 2 obstetrical units in Argentina on neonates born at term without complications to mothers with uneventful pregnancies. After written parental consents were obtained, newborns were randomly assigned to cord clamping within the first 15 seconds (group 1), at 1 minute (group 2), or at 3 minutes (group 3) after birth. The infants' venous hematocrit value was measured 6 hours after birth. RESULTS: Two hundred seventy-six newborns were recruited. Mean venous hematocrit values at 6 hours of life were 53.5% (group 1), 57.0% (group 2), and 59.4% (group 3). Statistical analyses were performed, and results were equivalent among groups because the hematocrit increase in neonates with late clamping was within the prespecified physiologic range. The prevalence of hematocrit at <45% (anemia) was significantly lower in groups 2 and 3 than in group 1. The prevalence of hematocrit at >65% was similar in groups 1 and 2 (4.4% and 5.9%, respectively) but significantly higher in group 3 (14.1%) versus group 1 (4.4%). There were no significant differences in other neonatal outcomes and in maternal postpartum hemorrhage. CONCLUSIONS: Delayed cord clamping at birth increases neonatal mean venous hematocrit within a physiologic range. Neither significant differences nor harmful effects were observed among groups. Furthermore, this intervention seems to reduce the rate of neonatal anemia. This practice has been shown to be safe and should be implemented to increase neonatal iron storage at birth.