Spinal cord lipomas: lessons learned in the era of total resection.

PURPOSE: Recent years have seen a paradigm shift towards total/near-total resection in spinal cord lipoma surgery. As this procedure is technically challenging, surgical candidates need to be selected appropriately through accurate image assessment and classification. The purpose of this paper is to describe a surgical series of paediatric spinal cord lipomas, their diagnosis, results and complications. METHODS: We undertook a retrospective review of paediatric patients with spinal cord lipomas who underwent surgery between 2008 and 2022. The variables studied were age, gender, preoperative symptoms according to the Necker Functional Score (NFS), type of lipoma according to Morota's classification, functional and radiological surgical outcomes using the cord-sac ratio (CSR), need for re-operation, complications and follow-up. RESULTS: A total of 25 patients (average age 36 months) underwent surgery. According to Morota's classification, MRI showed 13 type 1 lipomas, two type 2, two type 3 and eight type 4. The preoperative NFS was 16.06, with urological abnormalities being the most frequent manifestation. Total/near-total resection was attempted since 2015. Five patients with type 1 lipoma required re-operation due to clinical deterioration with suspected retethering, all of them with a CSR > 0.3. The series average CSR was 0.417. CONCLUSIONS: This paper highlights the importance of proper classification for a correct surgical approach to obtain favourable results and minimise possible complications. Based on our experience, given our results regarding the percentage of fistulae and retethering rates, we limited radical resection to symptomatic type 1 lipomas. Our future aim is to obtain better CSR rates and to decrease the retethering percentage.

Feasibility of a New Model of Care for Allogeneic Stem Cell Transplantation Recipients Facilitated by eHealth: The MY-Medula Pilot Study.

The use of allogeneic stem cell transplantation (allo-SCT) for the treatment of hematologic diseases is steadily increasing; however, allo-SCT has the downside of causing considerable treatment-related morbidity and mortality. Mobile technology applied to healthcare (mHealth) has proven to be a cost-effective strategy to improve care and offer new services to people with multimorbidity, but there are little data on its usefulness in allo-SCT recipients. Here we describe a new integrated healthcare model facilitated by an mHealth platform, EMMASalud-MY-Medula, and to report the results of a feasibility and usability pilot study. The MY-Medula platform was developed in 4 phases. First, patient and healthcare professional needs were identified, and technological development and pretesting tests were conducted (phases 1 to 3, January 2016 to March 2021). Then a nonrandomized, prospective, observational, single-center pilot study was conducted (October 2021 to January 2022) at the adult SCT unit of a tertiary university hospital. Twenty-eight volunteer allo-SCT recipients were included in the pilot study, of whom one-half were outpatients in the first-year post-SCT and one-half were affected by steroid-dependent graft-versus-host disease (SR-GVHD). All patients used the MY-Medula app during the 2-month follow-up period, with a median number of visits to the app of 143 (range, 6 to 477). A total of 2067 self-monitoring records were created, and 205 text messages were received, most of them related to symptoms description (47%) and doubts about medication (21%). In 3.4% of the cases, drug dosage was adjusted by the pharmacist because of dosing errors or interactions. At the end of the study, a 6-question Likert-type questionnaire for patients and a 22-question test for healthcare professionals showed a high degree of satisfaction (95% and 100%, respectively) with the new healthcare pathway. Reengineering the follow-up of allo-SCT recipients into an integrated, multidisciplinary model of care facilitated by mHealth tools is feasible and has been associated with high usability and a high degree of satisfaction by patients and healthcare professionals. A randomized trial aiming to determine the cost-effectiveness of MY-Medula-based follow-up post-SCT is currently enrolling participants.

Long-term transplant outcomes after allogeneic hematopoietic transplant in pediatric patients with hematological malignancies are influenced by severe chronic graft vs. host disease and immune reconstitution.

Long-term follow-up studies are crucial to ensure surveillance and intervention for late complications after allogeneic stem cell transplantation, but they are scarce on the pediatric population. This study aims to analyze risk factors for long-term transplant outcomes. We report a landmark analysis of 162 pediatric patients who underwent allogeneic transplantation between 1991 and 2016, and survived for at least 12 months after the transplant. With a median follow-up time of 10 years for the survivors, the probability of disease-free survival (DFS) and overall survival (OS) is 81 ± 3 and 88 ± 2%, respectively. Variables that influenced DFS in the univariate analysis were: disease phase (early phase 87 ± 3% vs. advanced phase 74 ± 5%; p = 0.04), acute graft vs. host disease (aGvHD; yes 73 ± 5% vs. no 87 ± 3%; p = 0.038), severe chronic GvHD (cGvHD; yes 41 ± 13% vs. no 85 ± 3%; p = 0.0001), and CD4+ lymphocytes 2 years after the transplant (above the median of 837/µl 98 ± 2% vs. below the median 82 ± 6%, p = 0.026). However, in the multivariate analysis, the only variable that influenced DFS was presence of severe chronic GvHD (yes vs. no, HR 6.25; 95% CI, 1.35-34.48; p = 0.02). Transplant strategies should aim to reduce the risk of severe cGvHD. Immune reconstitution surveillance may help clinicians to better deal with late transplant complications.

Competitividad de los gobiernos subnacionales y su relación con la mortalidad por COVID-19 en Perú / Competitiveness of subnational governments and their relationship with COVID-19 mortality in Peru

Introducción: La pandemia por COVID-19 ha puesto de manifiesto las grandes desigualdades en la población mundial. Objetivo: Describir la correlación entre la competitividad y la mortalidad por COVID-19 en el Perú, teniendo como elemento de estudio a los gobiernos subnacionales. Material y Métodos: Estudio observacional basado en el análisis secundario de las muertes por COVID-19 en el 2020 y el índice de competitividad regional de los gobiernos subnacionales 2019. Se calcularon: tasas bruta y estandarizada, índice de efecto y de desigualdad de la pendiente, diferencia y razón de tasas brutas y estandarizadas, riesgo atribuible poblacional, gradiente social, así como brechas relativas y absolutas de mortalidad por COVID-19. Resultados: En el año 2020, la tasa estandarizada de mortalidad por COVID-19 (TEM-COVID-19) fue 267,61 muertes x 105 habitantes. El 21,53 por ciento de la varianza de la TEM-COVID-19 es explicada por el índice de competitividad regional del año 2019 (p= 0,019); el índice de desigualdad de la pendiente fue 29,68 y, por cada punto en el INCORE 2019, la TEM-COVID-19 aumentó 100,78 puntos (R2a= 0,181). En el quintil 1 de competitividad regional, esta fue 151,83, mientras que en el quintil 5 llegó a 449,15. La brecha de desigualdad absoluta entre ambos quintiles fue 297,32 y alcanzó 2,95 en la brecha de desigualdad relativa. La curva de concentración evidenció la desigualdad socio geográfica de las muertes por COVID-19 en el año 2020. Conclusiones: La mortalidad por COVID-19 se incrementó a medida que aumentaba la competitividad de los gobiernos subnacionales evidenciando la desigualdad socio-geográfica del impacto de la pandemia(AU)

Introduction: The COVID-19 pandemic has revealed high disparities in the world population. Objective: To describe the correlation between competitiveness and mortality from COVID-19 in Peru, with subnational governments as an element of study. Material and Methods: Observational study based on the secondary analysis of deaths from COVID-19 that occurred in 2020 and the regional competitiveness index of subnational governments in 2019. The crude and standardized rates, the effect index, the difference and ratio of crude and standardized rates, the population attributable risk, the inequality gradient, and the relative and absolute gaps in mortality from COVID-19 were calculated. Results: In 2020, the standardized mortality rate for COVID-19 (COVID-19-SMR) was 267,61 deaths per 105 inhabitants. Additionally, 21,53 percent of the variance from the COVID-19-SMR is explained by the regional competitiveness index 2019 (p= 0,019); the slope inequality index was 29,68 and, for each point in the INCORE 2019, the COVID-19-SMR increased 100,78 points (R2a= 0,181). In quintile 1 of regional competitiveness, it was 151,83, while in quintile 5 it reached 449,15. The absolute inequality gap between both quintiles was 297,32 and it reached 2,95 in the relative inequality gap. The concentration curve evidenced the socio-geographic inequality of deaths from COVID-19 in 2020. Conclusions: Mortality increased as subnational governments became more competitive, evidencing the socio-geographical inequality of the impact of the COVID-19 pandemic(AU)

T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαß+/CD19+ Depletion Platforms.

Background: T-cell depleted (TCD) haploidentical transplantation using CD3+/CD19+ and TCRαß+/CD19+ depletion techniques has been increasingly used in children with hematological malignancies. We present a retrospective study aimed to compare transplant outcomes in children with leukemia receiving a TCD haploidentical transplant using either CD3+/CD19+ or TCRαß+/CD19+ platforms. Methods: A total of 159 children with leukemia (ALL=80) (AML=79) that received a TCD haploidentical transplantation using either CD3+/CD19+ (n=79) or TCRαß+/CD19+ (n=80) platforms between 2005 and 2020 were included. Median age was 9 years in both groups. There were no differences in patient, donor, and transplant characteristics between groups except for donor KIR B genotype more frequent in the TCRαß+/CD19+ group (91%) than in the CD3+/CD19+ group (76%) (p=0.009) and a high number of NK+ cells and lower CD19+ cells infused in the TCRαß+/CD19+ group (35.32x106/kg and 0.06 x106/Kg) than in the CD3+/CD19 group (24.6x106/Kg and 0.25 x106/Kg) (p=0.04 and p=0.0001), respectively. Conditioning was based on TBF. Median follow-up for survivors was 11 years (range; 8-16 y) in CD3+/CD19+ group and 5 years (range; 2-9 y) in the TCRαß+/CD19+ group. Results: Engraftment kinetics were similar in both groups (13 days for neutrophils and 10 days for platelets). There was no difference in the incidence of acute GvHD II-IV (29 ± 5% in the CD3+/CD19+ group vs 38 ± 5% in the TCRαß+/CD19+ group) and chronic GvHD (32 ± 5% vs 23 ± 4%, respectively). NRM was 23 ± 5% in the CD3+/CD19+group vs 21 ± 4% in the TCRαß+/CD19+group. Relapse incidence was also similar, 32 ± 5% vs 34 ± 6%, respectively. DFS and OS were not different (45 ± 5% vs 45 ± 6% and 53 ± 6% vs 58 ± 6% respectively). As there were no differences on transplant outcomes between groups, we further analyzed all patients together for risk factors associated with transplant outcomes. On multivariate analysis, we identified that early disease status at transplant (HR: 0.16; 95%CI (0.07-0.35) (p=0.0001), presence of cGvHD (HR: 0.38; 95%CI (0.20-0.70) (p= 0.002), and donor KIR-B genotype (HR: 0.50; 95%CI (0.32-0.90) (p=0.04) were associated with better DFS. Conclusions: Our data suggest that there are no advantages in transplant outcomes between TCD platforms. Risk factors for survival are dependent on disease characteristic, donor KIR genotype, and chronic GvHD rather than the TCD platform used.

Re-ventriculostomía endoscópica de tercer ventrículo. Análisis retrospectivo de una serie de 13 casos / Re-Do endoscopic third ventriculostomy. Retrospective analysis of 13 patients

Objetivos: La indicación de ventriculostomía endoscópica de tercer ventrículo (VET) en el tratamiento de la hidrocefalia no comunicante está extensamente aceptada. Existe controversia respecto a la indicación de un segundo procedimiento (re-VET) cuando el primero ha fallado. El objetivo de este trabajo es recoger los fallos de VET en una serie propia en los que se realizó re-VET y describir los factores relacionados con su pronóstico.MétodoEstudio retrospectivo de pacientes pediátricos con fallo de VET tratados mediante una re-VET entre 2003 y 2018. Se registró género, edad en primera y segunda VET, tiempo hasta fallo de primera VET, etiología de hidrocefalia, presencia previa de DVP, ETV-SS en primera y segunda VET, hallazgos intraoperatorios, éxito del segundo procedimiento y seguimiento. El resultado de ETV-SS se agrupó en puntuación alta (≥80), moderada (50-70) o baja (≤40). Se consideró fallo de procedimiento endoscópico el deterioro clínico o la ausencia de criterios radiológicos de mejoría (reducción de tamaño ventricular o presencia de artefacto de flujo de VET en área premamilar).ResultadosDe 97 VET realizadas en este periodo, se registraron 47 fallos, llevándose a cabo 13 re-VET. De ellas, 8 fueron clasificadas como éxito (61,53%). La re-VET fue exitosa en 4/4 casos cuya etiología fue tumoración tectal o estenosis de acueducto. En el grupo de alta puntuación ETV-SS hubo mayor porcentaje de éxito (75%) que en el grupo de moderada puntuación (40%). Nueve pacientes presentaban DVP previa a la primera VET y en ellos, el éxito fue del 66,6% frente al 50% en el grupo sin DVP previa. Todas las re-VET se llevaron a cabo sin complicaciones. En 11 de los 13 procedimientos se encontró una membrana premamilar cerrada y en los 2 casos restantes una apertura puntiforme. El seguimiento medio tras re-VET fue de 61,23 meses.ConclusiónLa re-VET es un procedimiento seguro y con una tasa de éxito del 61,5% en nuestra serie...(AU)

Objetives: Indication for endoscopic third ventriculostomy (ETV) in the treatment for noncommunicating hydrocephalus is widely accepted. There is controversy regarding the indication of a second procedure (re-ETV) when the first has failed. The objective of this work is to revise ETV failures in a series in which re-ETV was performed and to describe the factors related to its prognosis.MethodRetrospective study of pediatric patients with ETV failure treated by re-ETV between 2003 and 2018. Gender, age in first and second ETV, time to failure of first ETV, etiology of hydrocephalus, previous presence of shunt, ETV-SS in the first and second ETV, intraoperative findings, success of the second procedure and follow-up were collected. The ETV-SS result was grouped into high (≥80), moderate (50-70) or low (≤40) scores. Endoscopic procedure failure was considered clinical worsening or the absence of radiological criteria for improvement (reduction in ventricular size or presence of ETV flow artifact in the floor of third ventricle).ResultsOf 97 ETV carried out in this period, 47 failures were registered, with 13 re-ETV performed. Of these, 8 were classified as successful (61.53%). Re-ETV was successful in 4/4 cases in which etiology was tectal tumor or aqueduct stenosis. In the group with a high ETV-SS score there was a higher rate of success (75%) than in the group with a moderate score (40%). 9 patients presented shunt prior to first ETV and in them, success was 66.6% compared to 50% in the group without prior shunt. All re-ETV were performed without complications. In 11 of the 13 procedures a closed stoma was found and the remaining 2 cases, we found a punctate opening. The mean follow-up after re-ETV was 61.23 months.ConclusionThe selection of patients for re-VET should be cautious. Factors such as age, etiology, and previous shunt (ETV-SS factors) have prognostic influence. However... (AU)

Re-Do endoscopic third ventriculostomy. Retrospective analysis of 13 patients.

OBJETIVES: Indication for endoscopic third ventriculostomy (ETV) in the treatment for noncommunicating hydrocephalus is widely accepted. There is controversy regarding the indication of a second procedure (re-ETV) when the first has failed. The objective of this work is to revise ETV failures in a series in which re-ETV was performed and to describe the factors related to its prognosis. METHOD: Retrospective study of pediatric patients with ETV failure treated by re-ETV between 2003 and 2018. Gender, age in first and second ETV, time to failure of first ETV, etiology of hydrocephalus, previous presence of shunt, ETV-SS in the first and second ETV, intraoperative findings, success of the second procedure and follow-up were collected. The ETV-SS result was grouped into high (≥ 80), moderate (50-70) or low (≤ 40) scores. Endoscopic procedure failure was considered clinical worsening or the absence of radiological criteria for improvement (reduction in ventricular size or presence of ETV flow artifact in the floor of third ventricle). RESULTS: Of 97 ETV carried out in this period, 47 failures were registered, with 13 re-ETV performed. Of these, 8 were classified as successful (61.53%). Re-ETV was successful in 4/4 cases in which etiology was tectal tumor or aqueduct stenosis. In the group with a high ETV-SS score there was a higher rate of success (75%) than in the group with a moderate score (40%). 9 patients presented shunt prior to first ETV and in them, success was 66.6% compared to 50% in the group without prior shunt. All re-ETV were performed without complications. In 11 of the 13 procedures a closed stoma was found and the remaining 2 cases, we found a punctate opening. The mean follow-up after re-ETV was 61.23 months. CONCLUSION: The selection of patients for re-VET should be cautious. Factors such as age, etiology, and previous shunt (ETV-SS factors) have prognostic influence. However, there are specific factors which indicate favorable prognostic for re-VET such as a longer time to failure of the first procedure, the finding of a closed/punctate stoma or the loss of flow artifact in the follow-up MRI.

Acquisition Time for Swept-Source Optical Biometry Plus Corneal Power Measurement During Cataract Evaluation.

Purpose: To compare the acquisition time necessary to obtain the optical biometry plus corneal power measurement using the IOLMaster 700 with central topography with that found using the standard IOLMaster 700 in combination with two corneal topographers, when acquiring biometry measurements during cataract evaluation. Methods: This prospective, observational, controlled study included 96 eyes of 96 cataract patients. Acquisition times were registered for different conditions: time required for one complete measurement with IOLMaster 700 with central topography, time required for one complete measurement with standard IOLMaster 700 (without central topography), time required for one complete measurement with standard IOLMaster 700 plus time required for one complete measurement with Cassini, and time required for one complete measurement with standard IOLMaster 700 plus time required for one complete measurement with Pentacam HR. In addition, the agreement between keratometry (K), total keratometry (TK) and equivalent K reading (EKR) parameters using the three devices was performed. Results: The post hoc Tukey's test revealed that there were statistically significant differences for all pairwise comparisons (p < 0.001) except for the acquisition times of the IOLMaster with central topography and the standard IOLMaster 700 (p = 0.501). The acquisition time by the IOLMaster 700 with central topography takes approximately three less times than the use of a corneal topographer combined with a biometer. The agreement of K1, K2, TK1, TK2, EKR1 and EKR2 measurements between the three devices revealed statistically significant differences for all possible comparisons (p < 0.001) except for the comparison between the IOLMaster 700 and the Cassini for all parameters (p > 0.05). Conclusion: We consider that this is an efficient procedure that improves clinical flow. We also conclude that K readings obtained with the three devices cannot be used interchangeably since there are clinically relevant differences that may affect cataract surgery outcomes.

Defective DNA polymerase beta invoke a cytosolic DNA mediated inflammatory response.

Base excision repair (BER) has evolved to maintain the genomic integrity of DNA following endogenous and exogenous agent induced DNA base damage. In contrast, aberrant BER induces genomic instability, promotes malignant transformation and can even trigger cancer development. Previously, we have shown that deoxyribo-5'-phosphate (dRP) lyase deficient DNA polymerase beta (POLB) causes replication associated genomic instability and sensitivity to both endogenous and exogenous DNA damaging agents. Specifically, it has been established that this loss of dRP lyase function promotes inflammation associated gastric cancer. However, the way that aberrant POLB impacts the immune signaling and inflammatory responses is still unknown. Here we show that a dRP lyase deficient variant of POLB (Leu22Pro, or L22P) increases mitotic dysfunction associated genomic instability, which eventually leads to a cytosolic DNA mediated inflammatory response. Furthermore, poly(ADP-ribose) polymerase 1 inhibition exacerbates chromosomal instability and enhances the cytosolic DNA mediated inflammatory response. Our results suggest that POLB plays a significant role in modulating inflammatory signaling, and they provide a mechanistic basis for future potential cancer immunotherapies.

Comparison of clinical outcomes between unrelated single umbilical cord blood and "ex-vivo" T-cell depleted haploidentical transplantation in children with hematological malignancies.

BACKGROUND: Over the last two decades, umbilical cord blood (UCB) and haploidentical transplantation (HaploHSCT) have emerged as alternative sources of hematopoietic stem cell for allogeneic transplantation. There are few retrospective studies and no prospective studies comparing both types of alternative transplantation in pediatric patients. RESULTS: We analyzed the data of 134 children with hematological malignancies who received a hematopoietic stem cell transplantation from a single umbilical cord blood (UCB) (n = 42) or an "ex-vivo" T-cell depleted transplant from a haploidentical-related donor (HaploHSCT) (n = 92) between 1996 and 2014. Hematological recovery was faster after HaploHSCT than the UCB transplant group (median times to neutrophil and platelet recovery: 13 vs. 16 days, 10 vs. 57 days, respectively) (P < 0.001). The HaploHSCT group had a significantly early immune reconstitution based on NK and CD8 + T cells compared with the UCB group. However, after the first year post-transplantation, HaploHSCT had a lower number of CD4 + T and B lymphocytes compared with the UCB transplant recipients. The cumulative incidence of TRM was 29±8% in the HaploHSCT group versus 40±5% in the UCB group. Relapse incidence was 21±7% in the HaploHSCT group and 19±8% in the UCB group. Probability of DFS was 58±8% in the HaploHSCT group versus 40±9% in the UCB group (P = 0.051). CONCLUSIONS: TCD haploidentical transplant is associated with advantages in terms of engraftment and early immune reconstitution kinetics. TCD haploidentical transplant was associated with lower incidence of infectious and non-infectious complications, especially in the early phases of the transplant compared with UCB transplant recipients. However, there are no advantages in transplant outcomes compared with UCB transplant.

Prevalencia e incidencia de la infección por Toxoplasma gondii en mujeres embarazadas en el Departamento de Salud de Dénia (Alicante) / Prevalence and incidence of Toxoplasma gondii infection in pregnant women in Dénia Health Department (Alicante)

Objetivo: Identificar la seroprevalencia y estimar la incidencia de infección por Toxoplasma gondii en mujeres gestantes en el Departamento de Salud de Dénia (Alicante). Metodología: Estudio de prevalencia e incidencia, en el que se incluyeron todas las determinaciones analíticas serológicas para T. gondii realizadas a mujeres embarazadas en el primer trimestre de gestación durante el año 2018 en la red asistencial del Departamento de Salud de Dénia, excluyéndose las mujeres que no se realizaron la determinación analítica serológica. Para conocer la prevalencia se revisaron las determinaciones de inmunoglobulina (Ig) G anti-T. gondii al inicio del embarazo. Para estimar la incidencia se realizó un estudio longitudinal retrospectivo, en el que se incluyeron todas las mujeres seronegativas al inicio del embarazo mediante la determinación de IgM en los distintos trimestres de gestación. Resultados: Se incluyó un total de 1.419 mujeres gestantes. De todas ellas, se identificaron 234 (16%) con títulos protectores de IgG; 1.185 (84%) mujeres eran seronegativas al inicio del embarazo, entre las que se identificaron determinaciones IgM positivas en 22, calculándose una incidencia de primoinfección por T. gondii en mujeres embarazadas del 1,5%. Conclusión: El alto porcentaje de mujeres embarazadas que no han estado expuestas y la baja incidencia de toxoplasmosis en nuestro medio respaldan las recomendaciones actuales de las sociedades médicas y autoridades sanitarias, que abogan por no realizar un cribado sistemático y potenciar la prevención primaria de la enfermedad. (AU)

Objective: Know the seroprevalence and estimate the incidence of Toxoplasma gondii in pregnant women at Dénia Health Department (Alicante). Methodology: Prevalence and incidence study in which all serological analytical determinations for T. gondii carried out on pregnant women in the first trimester of gestation during 2018 were included in the healthcare network of the Dénia Health Department, excluding those women who were not carried out the serological analytical determination. To know the prevalence, the IgG anti-T. gondii determinations were reviewed at the beginning of pregnancy. To estimate the incidence, a retrospective longitudinal study was carried out in which all seronegative women were included at the beginning of pregnancy by means of IgM determination in the different gestation trimesters. Results: A total of 1,419 pregnant women were included. Of all of them, 234 (16%) pregnant women with protective IgG titles were identified, being 1,185 (84%) seronegative pregnant women at the beginning of pregnancy. Of the total of 1,185 pregnant women who were seronegative at the beginning of pregnancy, positive IgM determinations were identified in 22 of the pregnant women, calculating an incidence of primary infection by T. gondii in pregnant women of 1.5%. Conclusion: The high percentage of pregnant women who have not been exposed and the low incidence of toxoplasmosis in our environment, supports the current recommendations of medical societies and health authorities which advocate not carrying out a systematic screening promoting the primary prevention of the disease. (AU)

Re-Do endoscopic third ventriculostomy. Retrospective analysis of 13 patients. / Re-ventriculostomía endoscópica de tercer ventrículo. Análisis retrospectivo de una serie de 13 casos.

OBJETIVES: Indication for endoscopic third ventriculostomy (ETV) in the treatment for noncommunicating hydrocephalus is widely accepted. There is controversy regarding the indication of a second procedure (re-ETV) when the first has failed. The objective of this work is to revise ETV failures in a series in which re-ETV was performed and to describe the factors related to its prognosis. METHOD: Retrospective study of pediatric patients with ETV failure treated by re-ETV between 2003 and 2018. Gender, age in first and second ETV, time to failure of first ETV, etiology of hydrocephalus, previous presence of shunt, ETV-SS in the first and second ETV, intraoperative findings, success of the second procedure and follow-up were collected. The ETV-SS result was grouped into high (≥80), moderate (50-70) or low (≤40) scores. Endoscopic procedure failure was considered clinical worsening or the absence of radiological criteria for improvement (reduction in ventricular size or presence of ETV flow artifact in the floor of third ventricle). RESULTS: Of 97 ETV carried out in this period, 47 failures were registered, with 13 re-ETV performed. Of these, 8 were classified as successful (61.53%). Re-ETV was successful in 4/4 cases in which etiology was tectal tumor or aqueduct stenosis. In the group with a high ETV-SS score there was a higher rate of success (75%) than in the group with a moderate score (40%). 9 patients presented shunt prior to first ETV and in them, success was 66.6% compared to 50% in the group without prior shunt. All re-ETV were performed without complications. In 11 of the 13 procedures a closed stoma was found and the remaining 2 cases, we found a punctate opening. The mean follow-up after re-ETV was 61.23 months. CONCLUSION: The selection of patients for re-VET should be cautious. Factors such as age, etiology, and previous shunt (ETV-SS factors) have prognostic influence. However, there are specific factors which indicate favorable prognostic for re-VET such as a longer time to failure of the first procedure, the finding of a closed/punctate stoma or the loss of flow artifact in the follow-up MRI.

Optical and visual quality assessment of an extended depth-of-focus intraocular lens based on spherical aberration of different sign.

PURPOSE: To assess the optical quality and the visual performance of patients implanted with an extended depth-of-focus (EDOF) intraocular lens (IOL). METHODS: Thirty-eight eyes underwent implantation of the Mini WELL Ready EDOF IOL and were evaluated at 3-months postsurgery. Higher-order aberrations (HOAs) and modular transfer function (MTF) were measured at 3- and 5-mm pupils. Binocular uncorrected-distance visual acuity (UDVA) and corrected-distance visual acuity (CDVA), uncorrected-distance intermediate visual acuity (UIVA) and corrected-distance intermediate visual acuity (CDIVA) at 80 cm, and uncorrected-distance near visual acuity (UNVA) and corrected-distance near visual acuity (CDNVA) at 40 cm were obtained. Postoperative refraction, binocular defocus curve, halometry and subjective ad hoc patients' questionnaire were also evaluated. RESULTS: HOAs were 0.171 ± 0.046 µm and 0.406 ± 0.137 µm at 3 and 5 mm, respectively. MTFs decreased as the spatial frequency increased being comparable for both pupils. 92.10% of eyes were within ± 1.00D, and the mean postoperative spherical equivalent was - 0.25 ± 0.65D. Mean UDVA, UIVA and UNVA were 0.06 ± 0.12, 0.05 ± 0.10 and 0.26 ± 0.28 logMAR, respectively. Mean CDVA, CDIVA and CDNVA were - 0.01 ± 0.08, 0.06 ± 0.11 and 0.24 ± 0.12 logMAR, respectively. Defocus curve showed a continuous range of vision, especially at intermediate distances. Mean discrimination index was 0.79 ± 0.04. Questionnaire revealed that about 79% of patients reported a high or moderately high satisfaction with the procedure, and about 95% of patients would undergo the same procedure again. CONCLUSIONS: The Mini WELL Ready EDOF IOL provided good optical and visual quality with high level of patient satisfaction and seems to be a valuable option to provide unaided vision at different distances minimizing visual disturbances.

Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αß+ T-Cell Receptor and CD19+ Cell Depleted Grafts: High CD56dim/CD56bright NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome.

We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αß+ T-cell receptor/CD19+ depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed. Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR. Four patients developed graft failure. Median time to neutrophil and platelet recovery was 14 (range 9-25) and 10 days (range 7-30), respectively. The probability of non-relapse mortality (NRM) by day +100 after transplantation was 10 ± 4%. With a median follow-up of 28 months, the probability of relapse was 32 ± 6% and disease-free survival was 52 ± 6%. Immune reconstitution was leaded by NK cells. As such, a high CD56dim/CD56bright NK cell ratio early after transplantation was associated with better disease-free survival (DFS) (≥3.5; 77 ± 8% vs. <3.5; 28 ± 5%; p = 0.001) due to lower relapse incidence (≥3.5; 15 ± 7% vs. <3.5; 37 ± 9%; p = 0.04). T-cell reconstitution was delayed and associated with severe infections after transplant. Viral reactivation/disease and presence of venooclusive disease of liver in the non-caucasian population had a significant impact on NRM. αß+ T-cell receptor/CD19+ cell-depleted haploidentical transplant is associated with good outcomes especially in patients in early phase of disease. A rapid expansion of "mature" natural killer cells early after transplantation resulted on lower probability of relapse, suggesting a graft vs. leukemia effect independent from graft-vs.-host reactions.

Muerte súbita por disección de aorta torácica en jóvenes: estudio multicéntrico forense / Sudden death due to thoracic aortic dissection in young people: a multicenter forensic study

Introducción y objetivos: La disección de la aorta torácica (DAT) es infrecuente en jóvenes y presenta características diferentes que en la población adulta. En este estudio se analizan las características clinicopatológicas de la muerte súbita por DAT de personas de 1-35 años. Métodos: Estudio poblacional multicéntrico basado en autopsias forenses realizadas en las provincias de Vizcaya (periodo 1991-2016), Valencia (2000-2016) y Sevilla (2004-2016). Resultados: Se recogieron 35 casos (el 80% varones), con una media de edad de 29+/-5 años. La incidencia fue de 0,09/100.000 habitantes/año; 18 sujetos tenían algún factor de riesgo y 29, 1 o más factores de riesgo o hallazgos post mortem asociados con DAT: cardiopatía congénita (n=16), sospecha de DAT familiar (n=11), consumo de cocaína (n=6) e hipertensión arterial (n=5). En 24 casos, 12 con algún factor de riesgo, ya habían presentado síntomas previamente; 16 acudieron al médico, pero nunca hubo sospecha de DAT. El dolor torácico (n=12) fue el síntoma más frecuente. Los hallazgos autópsicos principales fueron: degeneración quística de la media (n=27), dilatación de la aorta ascendente (n=21), cardiomegalia (n=20) y válvula aórtica bicúspide (n=14). Conclusiones: La incidencia de muerte súbita por DAT fue muy baja. Los factores de riesgo más frecuentes fueron las cardiopatías congénitas, seguidas de la sospecha de DAT familiar y el consumo de cocaína. Se debería incluir la DAT en el diagnóstico diferencial del dolor torácico en jóvenes, principalmente varones, con factores de riesgo asociados

Introduction and objectives: Thoracic aortic dissection (TAD) is infrequent in young people and its characteristics differ from those in the adult population. This study aimed to analyze the clinical and pathological characteristics of sudden death due to TAD in people aged 1 to 35 years. Methods: Multicenter population-based study based on forensic autopsies conducted in the provinces of Biscay (1991-2016), Valencia (2000-2016), and Seville (2004-2016). Results: We identified 35 individuals with sudden death due to TAD (80% males), with a mean age of 29+/-5 years. The incidence was 0.09/100 000 inhabitants/y. Eighteen persons had at least 1 risk factor for TAD, and this figure increased to 29 when postmortem findings were included: congenital heart disease (n=16), suspicion of familial TAD (n=11), cocaine use (n=6), and hypertension (n=5). Twenty-four individuals, 12 with at least 1 risk factor, had prodromal symptoms, and 16 of them visited their physician, but TAD was not suspected in any of them. The most frequent symptom was chest pain (n=12). The main autopsy findings were cystic degeneration of the media (n=27), dilatation of the ascending aorta (n=21), cardiac hypertrophy (n=20), and bicuspid aortic valve (n=14). Conclusions: The incidence of sudden death due to TAD in young people was very low. The most frequent risk factors were congenital heart disease followed by suspicion of familial TAD and cocaine use. TAD should be included in the differential diagnosis of chest pain in young people, mainly male patients with at least 1 risk factor

Kinetics and Risk Factors of Relapse after Allogeneic Stem Cell Transplantation in Children with Leukemia: A Long-Term Follow-Up Single-Center Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment for high-risk hematological malignancies in the pediatric population, but relapse remains the leading cause of death. We analyzed risk factors associated with relapse. Data from 353 allo-HSCTs from 1989 to 2015 in our center were studied retrospectively. We performed a multivariate analysis of pre- and postransplantation variables and developed a predictive risk score for relapse using the significant factors in this training cohort. The results were confirmed in a validation cohort of 90 allo-HSCTs done in our institution from 2016 to the present. A total of 104 patients relapsed after allo-HSCT, with a relapse cumulative incidence of 31 ± 2%. In multivariate analysis, only 2 variables influenced relapse: disease phase (advanced versus early, HR, 2.84; 95% CI, 1.76 to 4.57; P = .001) and presence of chronic graft-versus-host disease (GVHD) (acute GVHD versus chronic GVHD [HR, 4.27; 95% CI, 1.99 to 9.15; P = .0001] and no GVHD versus chronic GVHD [HR, 6.86; 95% CI, 3.63 to 12.97] P = .0001]. Applying the personalized risk score (0 to 3), the relapse cumulative incidence was 70 ± 5% in patients with a score of 3 (without GVHD and in the advanced phase) compared with 6 ± 4% in patients with a score of 0 (with chronic GVHD and in an early phase). This score has been verified in the validation set. With a median follow-up of 54 months, the disease-free survival (DFS) and overall survival rate were 37 ± 3% and 45 ± 4%, respectively. The association of GVHD with the graft-versus-leukemia effect is clearly established in our study, and the form of GVHD associated with less relapse and the best DFS is the classical form of chronic GVHD according to the National Institutes of Health classification. The proposed relapse risk score was validated in an independent cohort and allows personalization of the prognosis.

Sudden Death Due to Thoracic Aortic Dissection in Young People: A Multicenter Forensic Study.

INTRODUCTION AND OBJECTIVES: Thoracic aortic dissection (TAD) is infrequent in young people and its characteristics differ from those in the adult population. This study aimed to analyze the clinical and pathological characteristics of sudden death due to TAD in people aged 1 to 35 years. METHODS: Multicenter population-based study based on forensic autopsies conducted in the provinces of Biscay (1991-2016), Valencia (2000-2016), and Seville (2004-2016). RESULTS: We identified 35 individuals with sudden death due to TAD (80% males), with a mean age of 29±5 years. The incidence was 0.09/100 000 inhabitants/y. Eighteen persons had at least 1 risk factor for TAD, and this figure increased to 29 when postmortem findings were included: congenital heart disease (n=16), suspicion of familial TAD (n=11), cocaine use (n=6), and hypertension (n=5). Twenty-four individuals, 12 with at least 1 risk factor, had prodromal symptoms, and 16 of them visited their physician, but TAD was not suspected in any of them. The most frequent symptom was chest pain (n=12). The main autopsy findings were cystic degeneration of the media (n=27), dilatation of the ascending aorta (n=21), cardiac hypertrophy (n=20), and bicuspid aortic valve (n=14). CONCLUSIONS: The incidence of sudden death due to TAD in young people was very low. The most frequent risk factors were congenital heart disease followed by suspicion of familial TAD and cocaine use. TAD should be included in the differential diagnosis of chest pain in young people, mainly male patients with at least 1 risk factor.

Prostaglandins induce early growth response 1 transcription factor mediated microsomal prostaglandin E2 synthase up-regulation for colorectal cancer progression.

Cyclooxygenase2 (COX2) has been associated with cell growth, invasiveness, tumor progression and metastasis of colorectal carcinomas. However, the downstream prostaglandin (PG)-PG receptor pathway involved in these effects is poorly characterized.We studied the PG-pathway in gene expression databases and we found that PTGS2 (prostaglandin G/H synthase and cyclooxygenase) and PTGES (prostaglandin E synthase) are co-expressed in human colorectal tumors. Moreover, we detected that COX2 and microsomal Prostaglandin E2 synthase 1 (mPGES1) proteins are both up-regulated in colorectal human tumor biopsies.Using colon carcinoma cell cultures we found that COX2 overexpression significantly increased mPGES1 mRNA and protein. This up-regulation was due to an increase in early growth response 1 (EGR1) levels and its transcriptional activity. EGR1 was induced by COX2-generated PGF2α. A PGF2α receptor antagonist, or EGR1 silencing, inhibited the mPGES1 induction by COX2 overexpression. Moreover, using immunodeficient mice, we also demonstrated that both COX2- and mPGES1-overexpressing carcinoma cells were more efficient forming tumors.Our results describe for the first time the molecular pathway correlating PTGS2 and PTGES in colon cancer progression. We demonstrated that in this pathway mPGES1 is induced by COX2 overexpression, via autocrine PGs release, likely PGF2α, through an EGR1-dependent mechanism. This signaling provides a molecular explanation to PTGS2 and PTGES association and contribute to colon cancer advance, pointing out novel potential therapeutic targets in this oncological context.

Laparoscopic incisional hernia repair in an ambulatory surgery-extended recovery centre: a review of 259 consecutive cases.

PURPOSE: The high prevalence of incisional hernias and an average stay of 3-10 days for open procedures have made this pathology both a health problem and an economic issue. A protocol was developed for performing this procedure in an Ambulatory Surgery Center (ASC) with extended recovery. METHODS: From January 2000 to December 2011, data about all laparoscopic incisional hernia repairs were gathered prospectively. The patients' clinical features, hernia type, intraoperative and postoperative complications and reasons for hospital admission are studied. RESULTS: A total of 259 patients have been operated for incisional hernia (185) or recurrent hernioplasty (74) in our ASC. Laparoscopic repair was successful in 254 patients (98.07 %). Conversion to open surgery was necessary in five patients (1.93 %). A total of 50 patients (19.69 %) in whom surgery was completed laparoscopically were discharged the same day of surgery, 179 (70.47 %) at 24 h and 25 (9.84 %) required a stay of over 24 h. Postoperative pain was severe in 10 % of patients, moderate in 40 %, and mild in 50 %. Complications, mostly minor and self-limiting, were observed in 25 patients (9.84 %) during hospital stay. Five major complications that occured were: bile peritonitis, an acute peritonitis, due to an inadvertent intestinal perforation, and one intestinal obstruction by partial detachment of the mesh, an intra-abdominal hematoma and a colo-cutaneous fistula. There were no deaths in the series. The mean follow-up of patients was 29.35 months (range 12-129 months). The recurrence rate was 7.03 % (n = 18). Four trocar-site hernias were detected. CONCLUSIONS: It is essential to create a protocol with selection criteria that take into account the patient, his entourage, the anesthetic-surgical procedure, and a team dedicated to surgical laparoscopic surgery in an ASC with extended recovery to achieve good results in terms of morbidity and patient safety.