Long-Term Effects of Adipose-Derived Stem Cells for the Treatment of Bilateral Limbal Stem Cell Deficiency.

PURPOSE: To determine the safety and feasibility of human autologous adipose tissue-derived adult mesenchymal stem cells (ASCs) for ocular surface regeneration in patients with bilateral limbal stem-cell deficiency (LSCD). METHODS: A phase IIa clinical trial was designed (https://Clinicaltrials.gov, NCT01808378) with 8 patients, 3 of whom had aniridia, 2 meibomian glands diseases, 2 multiple surgeries and 1 chronic chemical injury. The therapeutic protocol was as follows: 6-mm of central corneal epithelium was removed, 400,000 ASCs were injected into each limboconjunctival quadrant, 400,000 ASCs were suspended over the cornea for 20 min, and finally the cornea was covered with an amniotic membrane patch. RESULTS: No adverse events were detected after a mean of 86,5 months of follow-up. One year after surgery, 6 of the 8 transplants were scored as successful, five patients had improved uncorrected visual acuity (mean of 12 letters), two patients presented epithelial defects (also present at baseline) and the mean percentage of corneal neovascularization was of 28.75% (36.98%, at baseline). Re-examination 24 months after treatment disclosed preserved efficacy in 4 patients. At the last visit (after a mean of 86,5 months of follow up) epithelial defects were absent in all patients although improvement in all of the variables was only maintained in patient 3 (meibomian glands agenesia). CONCLUSION: ASCs are a feasible and conservative therapy for treating bilateral LSCD. The therapeutic effect differs between etiologies and diminishes over time.

Mapping the complexity and diversity of tertiary lymphoid structures in primary and peritoneal metastatic gastric cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in GC with poor prognosis and limited treatment response. We, therefore, hypothesize that immune cell composition and function of TLS depends on tumor location and the tumor immune environment. METHODS: Spatial transcriptomics and immunohistochemistry were used to characterize the phenotype of CD45+ immune cells inside and outside of TLS using archival resection specimens from GC primary tumors and peritoneal metastases. RESULTS: We identified significant intrapatient and interpatient diversity of the cellular composition and maturation status of TLS in GC. Tumor location (primary vs metastatic site) accounted for the majority of differences in TLS maturity, as TLS in peritoneal metastases were predominantly immature. This was associated with higher levels of tumor-infiltrating macrophages and Tregs and less plasma cells compared with tumors with mature TLS. Furthermore, mature TLSs were characterized by overexpression of antitumor immune pathways such as B cell-related pathways, MHC class II antigen presentation while immature TLS were associated with protumor pathways, including T cell exhaustion and enhancement of DNA repair pathways in the corresponding cancer. CONCLUSION: The observation that GC-derived peritoneal metastases often contain immature TLS which are associated with immune suppressive regulatory tumor-infiltrating leucocytes, is in keeping with the lack of response to immune checkpoint blockade and the poor prognostic features of peritoneal metastatic GC, which needs to be taken into account when optimizing immunomodulatory strategies for metastatic GC.

Interobserver Reliability and Sensitivity to Change of a Composite Ocular Inflammatory Activity Index: UVEDAI©.

INTRODUCTION: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment. METHODS: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test. RESULTS: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit. CONCLUSIONS: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.

Peripheral ulcerative keratitis as presenting manifestation of systemic microscopic polyangiitis: a case report / Ceratite ulcerativa periférica como manifestação de poliangiíte microscópica sistêmica: relato de caso

ABSTRACT Microscopic polyangiitis is a rare autoimmune disease of unknown etiology, characterized by inflammation and necrosis of blood vessels. It forms a part of the antineutrophil cytoplasmic antibody-associated vasculitides-a heterogeneous group of disorders characterized by vasculitis. It is a systemic disease affecting multiple organs. The patients may present with a wide variety of symptoms. Ocular manifestations may present as its initial clinical symptoms, necessitating a multidisciplinary approach for reducing the morbidity and mortality. Early diagnosis aids in the formulation of appropriate treatment and prevention of further complications. Aggressive treatment, including surgery, is often necessary to limit structural damage and preserve visual function. We present the case of an 82-year-old woman who initially presented with peripheral ulcerative keratitis that led to the diagnosis of microscopic polyangiitis.

RESUMO A poliangeíte microscópica é uma doença autoimune rara de etiologia desconhecida, caracterizada por inflamação e necrose dos vasos sanguíneos. Faz parte das vasculites associadas a anticorpos citoplasmáticos antineutrófilos - um grupo heterogêneo de doenças caracterizadas por vasculite. É uma doença sistêmica que afeta vários órgãos. Os pacientes podem apresentar uma grande variedade de sintomas. As manifestações oculares podem apresentar-se como seus sintomas clínicos iniciais, necessitando de abordagem multidisciplinar para redução da morbimortalidade. O diagnóstico precoce ajuda na formulação do tratamento adequado e na prevenção de complicações futuras. O tratamento agressivo, incluindo cirurgia, muitas vezes é necessário para limitar o dano estrutural e preservar a função visual. Apresentamos o caso de uma mulher de 82 anos que inicialmente apresentou ceratite ulcerativa periférica que levou ao diagnóstico de poliangite microscópica.

An ethnobotanical survey of medicinal plants used by inhabitants of Holguín, Eastern Region, Cuba / Estudio etnobotánico de las plantas medicinales usadas por los habitantes de Holguín, Región Oriental, Cuba

The present study was aimed to archive the etnhnomedicinal knowledge of plants used by inhabitants of seven villages of Holguín, Eastern region, Cuba. The ethnomedicinal information was collected through interviews. The collected data were analyzed through use value (UV), informant consensus factor (Fic) and fidelity level (FL). A total of 195 species of plants distributed in 166 genera belonging to 70 families were identified for the treatment of 17 ailment categories. The most treated conditions were digestive and liver disorders. The most important species according to their use value were Lippia alba (Mill.) N.E. Br. ex Britton & P. Wilson (0.236) and Annona muricata L. (0.194). Cancer and tumors had the Fic value of 0.94. A total of 19 species has a highest FL of 100 percent. This was the first ethnobotanical survey conducted in Holguín region, which will contribute to preserve valuable information of medicinal plants that may otherwise be lost to future generations.

El presente estudio tuvo como objetivo registrar el conocimiento etnomedicinal de las plantas usadas por los pobladores en 7 comunidades de Holguín, Región Oriental, Cuba. La información fue recogida a través de entrevistas y analizada cuantitativamente mediante indicadores etnobotánicos: valor de uso (UV), factor del consenso de los informantes (Fic) e índice de fidelidad (FL). Fueron reportadas un total de 195 especies de plantas, distribuidas en 166 géneros y 70 familias, para el tratamiento de 17 categorías de usos. Las indicaciones más frecuentes fueron los problemas digestivos y del hígado. Las especies medicinales con mayor UV fueron Lippia alba (Mill.) N.E. Br. ex Britton & P. Wilson (0.236) y Annona muricata L. (0.194). Cáncer y tumores tuvieron el valor más alto de Fic (0.94). Solo 19 especies presentaron un valor de FL de 100 %. Este primer estudio contribuirá a preservar la información de las plantas medicinales y que esta no se pierda en las futuras generaciones.

Prevalencia de disfunción eréctil y factores asociados en pacientes con indicación de rehabilitación cardíaca / Erectile dysfunction in patients referred for cardiac rehabilitation: prevalence and associated factors

Introducción: La disfunción eréctil (DE) afecta a millones de personas en el mundo. Se caracteriza por daño endotelial vascular y actualmente es considerado un marcador de riesgo de enfermedad cardiovascular. Sin embargo, no es evaluada normalmente por el personal médico y los pacientes se rehúsan a discutirlo. El objetivo de este trabajo es determinar la prevalencia de DE y sus factores asociados en pacientes con indicación de rehabilitación cardíaca. Material y Método: Estudio descriptivo, transversal, incluyó 225 pacientes con indicación de rehabilitación cardíaca de 6 países de Latinoamérica: Chile (CH), Brasil (BR), Perú (PE), Colombia (CO), Argentina (AR) y Paraguay (PY) en el período de marzo-agosto 2014. Se obtuvo datos demográficos y se utilizó el cuestiona-rio Índice Internacional de Función Eréctil (CIIFE) auto administrado. Las variables fueron procedencia, edad, peso, talla, IMC, obesidad, hipertensión arterial (HTA), diabetes mellitus (DM), infarto agudo del miocardio (IAM), tabaquismo y uso de fármacos. Resultados: Se evaluó a 225 hombres. De acuerdo al CIIFE, 80,1% tuvo algun tipo de DE; 8,9% severa; 10,7% moderada; 26,2% media a moderada y 35,6% media. Los factores asociados significativamente fueron el país de procedencia, la DM, la edad y el tabaquismo. Conclusión: La prevalencia de Disfunción Eréctil en pacientes con indicación de rehabilitación cardíaca de Chile, Brasil, Perú, Colombia, Argentina y Paraguay fue 80,1% y sus factores asociados son edad, obesidad, IAM, DM, HTA y tabaquismo.

Background: Erectile dysfunction (ED) affects millions of males around the world. It is characterized by endothelial dysfunction and is currently considered to be a marker of cardiovascular disease. However, it is seldom evaluated by medical personnel and patients frequently refuse to discuss the subject. The aim of this investigation was to determine incidence and prevalence of ED and associated factors in patients referred for cardiac rehabilitation. Method: A descriptive, cross sectional study was performed in 225 patients referred for cardiac rehabilitation in 6 Latin American countries: Chile (CH), Brazil (BR), Perú (PE), Colombia (CO), Argentina (AR) and Paraguay (PY), from March to August 2014. Demographic data were collected and the self-administered International ED questionnaire was applied to evaluate ED. Variables included age, weight, height, BMI, obesity, hypertension (HT), diabetes mellitus (DM), acute myocardial infarction, smoking habit and use of different medications Results: 80.1% of subjects had some type of ED: it was severe in 8.9%, moderate in 10.7%. moderate to intermediate in 26.2% and intermediate in 35.6%. Factors associated to the presence of ED were country of origin, DM, age, and smoking habit Conclusion: ED was present in a mean of 80.1% of patients referred for cardiac rehabilitation in Chile, Brazil, Perú, Colombia, Argentina, and Paraguay. ED was associated to age, obesity, myocardial infarction, DM, HT, and smoking habit.

Síndrome de respuesta inflamatoria sistémica y disfunción orgánica en urgencias pediátricas / Association between systemic inflammatory response and organ dysfunction in paediatric emergencies

En las salas de Emergencias Pediátricas la gravedad o el riesgo de fallecer es un hecho de especial importancia. La gravedad de una enfermedad es difícil de definir, para esto, se han desarrollado escalas de riesgo de muerte. Para optimizar la preparación del departamento de emergencia en el manejo de niños con enfermedades graves necesitamos conocer las características del paciente y su enfermedad. Objetivo: Evaluar relación entre síndrome de respuesta inflamatoria sistémica y disfunción orgánica en niños Metodología: Cohorte prospectiva. Niños con enfermedad aguda grave, admitidos en forma consecutiva al departamento de urgencias, evaluación de variables clínicas y fisiológicas. Análisis del efecto de variables sobre el riesgo de disfunción orgánica múltiple o mortalidad Resultados: Riesgo de enfermedad aguda grave, 70/105 niños <12 años; edad mediana 0,9 (0,3-3,9) años; síndrome de disfunción orgánica múltiple, 14 (24,1%) de 58; tasa de mortalidad observada 6,9%. Riesgo de muerte en niños con disfunción multiorgánica 3/14 (21,4%) contra 1(2,3%) de 44 niños sin disfunción multiorgánica (RR 9,4; χ2 6,1; p 0,04) Conclusión: En niños con enfermedad aguda grave el riesgo de muerte esta positivamente asociado con el riesgo de disfunción orgánica múltiple.

In pediatric emergency rooms, the risk of dying is a fact of particular importance. The severity of a disease is difficult to define, for this reason, risk of death scales have been developed. To optimize the preparation of emergency departments in the management of children with serious diseases we need to know the characteristics of the patient and his illness. Goal: To assess the relationship between systemic inflammatory response syndrome and organ dysfunction in children Methodology: Prospective cohort. Children with serious acute illness, admitted consecutively to the Emergency Department, evaluation of clinical and physiological variables. Analysis of the effect of variables on the risk of mortality and multiple organ dysfunction Results: Serious risk of acute illness, 70/105 children < 12 years; age median 0.9 (0, 3-3, 9) years; multiple organ dysfunction syndrome, 14 (24.1%) 58; rate 6.9% observed mortality. Risk of death in children with dysfunction multi-organ 3/14 (21.4%) against 1(2,3%) of 44 children without multiple organ dysfunction (RR 9.4; ) χ2 ( 6.1; p 0.04) Conclusion: In children with acute and severe illnesses, the risk of death is positively associated with the risk of multiple organ dysfunction.

Validación de dos escalas de valor pronóstico en niños que ingresan a UCI / Validation of two prediction value scores in children admitted to the intensive care unit

Las escalas PIM (Índice de Mortalidad Pediátrica) y PELOD (Índice Pediátrico de Disfunción Orgánica) son sistemas de evaluación que permiten la estimación de la severidad de la enfermedad y el ajuste del riesgo de mortalidad en grupos heterogéneos de pacientes. El objetivo del presente trabajo fue el de validar las escalas PIM y PELOD en una Unidad de Cuidados Intensivos pediátrica (UCIP). Metodología. Fueron incluidos 97 niños con edad menor o igual a 12 años; las variables estudiadas fueron la mortalidad o sobrevida durante la estancia en UCI. PIM incluye 7 variables medidas durante la primera hora de admisión a UCI; PELOD incluye disfunción de seis sistemas orgánicos en 12 variables. Para estimar discriminación, se utilizó el área bajo la curva de rendimiento diagnóstico, y para evaluar calibración, la bondad de ajuste de Hosmer-Lemeshow. Resultados. Edad media 4,0 años (rango intercuartil 1,0-8,1); estancia 6,0 días; (rango 3,0 a 17,0); las principales causas de ingreso a UCIP fueron accidentes 30, sepsis 19, neurológicas 14. Desarrollaron disfunción orgánica múltiple 58 (59,8%) de 97. La mortalidad observada fue de 17,5%. La predicción de riesgo de mortalidad por PIM fue significativamente más alta en no sobrevivientes (0,48±0,35) que sobrevivientes (0,18±0,23; t test 3,40 p<0,003); calibración (p=0,025) y discriminación (área bajo la curva = 0,79 ± 0,057; p<0,001) de PIM fue buena. Conclusión: PIM es una medida válida de predicción de riesgo de mortalidad en UCIP en nuestro medio

The Pediatric Index of Mortality (PIM) and Pediatric Logistic Organ Dysfunction (PLOD) scale are scoring systems that allow assessment of the severity of illness and mortality risk adjustment in heterogeneous groups of patients. The aim of this study was to validate the accuracy and reliability of PIM and PELOD scoring in a pediatric Intensive Care Unit (ICU) Methods: 97 children under 12 years of age were included. Survival and mortality during the stay in the ICU were studied. PIM scale includes 7 parameters measured during the first hour of admission to the ICU; PELOD includes dysfunction of 6 organs and systems in 12 variables. The area under the curve was used to assess discrimination and calibration was assessed with the Hosmer-Lemeshow goodness of fit test. Results: The median patient age was 4,0 years (inter-quartile range 1,0-8,1), median length of stay was 6 days (range 3-17). Main causes for admission to the ICU were accidents 30, sepsis 19, neurological 14. Fifty eight patients (59,8%) developed multiple organic dysfunction. Observed mortality was 17,5%. Prediction of risk of mortality with PIM was significantly higher in non survivors (0,48 ± 0,35) than in survivors (0,18 ± 0,23); t test 3,40 p<0,003; calibration (p=0,025) and discrimination (area under the curve = 0,79±0,057; p<0,001) for PIM was good. Conclusions: PIM is a valid prediction index for mortality risk in pediatric ICU in our hospitals

Eficacia del transplante autologo intracoronario de células madre CD34+ en pacientes con infarto de miocardio antiguo / Efficacy of intracoronary autologous transplantation of CD34+ stem cells in patients with old myocardial infarction

Antecedentes: la recuperación o mejoramiento de la función cardiaca en pacientes con infarto de miocardio antiguo se limita al manejo farmacológico y de rehabilitación. La terapia de células madre podría incrementar la función cardiaca en estos pacientes. Objetivos: determinar el grado de efectividad para recuperar la función cardiaca mediante el transplante de células madre en pacientes con infarto de miocardio antiguo. Método: ensayo clínico sin grupo de control en pacientes con infarto de miocardio antiguo de la menos cinco meses, a quienes se realiza un transplante de células madres por vía transcoronaria. Resultados: todos los pacientes mejoraron su función cardiaca y otros parámetros cardíacos; la Fracción de Eyección (FE) se incremento en un 30 por ciento en promedio en los pacientes entre el valor basal y los 06 meses; también se observó mejora en la Pureba de esfuerxo graduada (PEG) del 10 por ciento y en el consumo de METS en 20 por ciento. Conclusiones: La terapia con células madre CD34+ mejora la función cardiaca y la capacidad funcional.

Background: recovery or improvement of cardiac function in patients with old myocardial infarction is limited to medication management and rehabilitation. The stem cell therapy could improve cardiac function in these patients. Objectives: To determinate the degree of effectiveness to restore heart function by transplanting stem cells in patients with old myocardial infarction. Method: A clinical trial without control group in patients with old myocardial infarction at least five months, who underwent a transplant of stem cells through transcoronaria. Results: All patients improved their cardiac function and other parameters Cardiac Ejection Fraction (EF) was increased by 30 per cent on average in patients between baseline and 06 months, there was also improvement in the stress test graduated (PEG) 10 per cent and METS consumption by 20 per cent. Conclusions: Therapy with CD34+ stem cells improves cardiac function and functional capacity.