A zebrafish model of Ifih1-driven Aicardi-Goutières syndrome reproduces the interferon signature and the exacerbated inflammation of patients.

Type I interferonopathies are a heterogenic group of rare diseases associated with an increase in type I interferon (IFN). The main challenge for the study of Type I interferonopathies is the lack of a well-founded animal model to better characterize the phenotype as well as to perform fast and large drug screenings to offer the best treatment options. In this study, we report the development of a transgenic zebrafish model of Type I interferonopathy overexpressing ifih1 carrying the mutation p.Arg742His (Tg(ifih1_mut)), corresponding to the human mutation p.Arg779His. RNA sequence analysis from Tg(ifih1_mut) larvae revealed a systemic inflammation and IFN signature upon a suboptimal poly I:C induction compared with wild-type larvae, confirming the phenotype observed in patients suffering from Type I interferonopathies. More interestingly, the phenotype was manifested in the zebrafish inflammation and Type I IFN reporters nfkb:eGFP and isg15:eGFP, respectively, making this zebrafish model suitable for future high-throughput chemical screening (HTS). Using the unique advantages of the zebrafish model for gene editing, we have generated Tg(ifih1_mut) knocked down for mavs and ikbke, which completely abrogated the Poly I:C induction and activation of the GFP of the reporters. Finally, we used an FDA-approved drug, Baricitinib (Jak1/Jak2 inhibitor), which was able to reduce the inflammation and the ISG expression. Our results demonstrate the potential of this model to further understand AGS pathological mechanisms and to identify novel therapeutic drugs by HTS.

Successful desensitisation to paclitaxel with omalizumab.

We present the case of a patient with failed desensitisation to paclitaxel that was ultimately successful with omalizumab treatment. Our patient, a female aged between 20-25 and diagnosed with a triple negative breast cancer, received first-line treatment with carboplatin and paclitaxel. During the second cycle of paclitaxel, she experienced heat, dyspnoea, facial angioedema and vomiting. Skin tests for allergic reactions returned negative results, and drug provocation tests showed a positive result (anaphylaxis). Rapid drug desensitisation (RDD) was carried out with two bags of dilutions but at the beginning of the infusion, the patient experienced symptoms again, so the infusion was stopped. Therefore, the use of omalizumab, already reported as a successful adjuvant in desensitisation to other drugs, was considered. The anti-immunoglobulin E (IgE) monoclonal antibody was administered off-label before the first programmed desensitisation with success: total dose of paclitaxel was infused without any reaction. The patient was able to receive the complete chemotherapy treatment.

ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome.

Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress-induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA-approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases.

[Marjolin's ulcer associated with verrucous carcinoma in an immunocompromised patient]. / Úlcera de Marjolin asociada a carcinoma verrugoso en paciente inmunocomprometido.

Background: Marjolin's ulcer is the malignant degeneration of any chronic wound, with a latency period from tissue injury to variable malignant transformation that may occur up to 30 years later. Among the associated neoplasms, squamous cell carcinoma (SCC) is the predominant lineage in up to 71% of cases. The verrucous carcinoma variant has been estimated to have a low presentation, being described in the literature as 2% of all SCC and reported anecdotally in immunosuppressed patients, which justifies the objective of this publication. Clinical case: 65-year-old female patient with a history of being a carrier of human immunodeficiency virus (HIV) infection, who presented a verrucous carcinoma associated to a Marjolin ulcer secondary to herpes zoster and infection of soft tissues in the right leg, with a latency period of 10 years from the initial infectious process to histopathological confirmation. Conclusions: The finding of a verrucous carcinoma on a Marjolin ulcer has been little described in literature, with a lower incidence in the context of a patient with a history of being a carrier of HIV infection, finding 7 case reports, the oldest from 1998. For this reason, it is important to have diagnostic suspicion, to carry out an adequate study protocol and always making clinical-pathological correlation, in order to establish timely and individualized treatment.

Introducción: la úlcera de Marjolin es la degeneración maligna de cualquier herida crónica, con un periodo de latencia desde la lesión tisular a la transformación maligna variable que puede presentarse hasta 30 años después. De las neoplasias asociadas, el carcinoma espinocelular es la estirpe predominante hasta en 71% de los casos. La variante de carcinoma verrugoso se ha estimado con una presentación baja, pues ha sido descrito en la literatura como el 2% de todos los carcinomas espinocelulares y reportado de manera anecdótica en pacientes inmunosuprimidos, lo que justifica el objetivo de esta publicación. Caso clínico: mujer de 65 años con el antecedente de ser portadora de infección por virus de inmunodeficiencia humana (VIH), que presentó un carcinoma verrugoso asociado a una úlcera de Marjolin secundaria a herpes zóster e infección de tejidos blandos en pierna derecha, con un periodo de latencia de 10 años desde el proceso infeccioso inicial hasta la confirmación histopatológica. Conclusiones: el hallazgo de un carcinoma verrugoso asentado sobre una úlcera de Marjolin ha sido poco descrito en la literatura, con una menor incidencia en el contexto de un paciente con antecedente de ser portador de infección por VIH, ante lo cual encontramos 7 reportes de caso, el más antiguo de 1998. Por este motivo es importante contar con la sospecha diagnóstica, para poder hacer un protocolo de estudio adecuado y siempre haciendo correlación clínico-patológica, con la finalidad de instaurar un tratamiento oportuno e individualizado.

Factors associated with hemoglobin levels in children under 6 months of age hospitalized in a pediatric center in Peru / Factores asociados a los niveles de hemoglobina en niños menores de 6 meses de edad hospitalizados en un centro pediátrico de Perú

Introduction: Anemia is a condition in which there is a low concentration of hemoglobin (Hb) levels. Although many causes of anemia have been identified, there are few studies in which they are related to epidemiological factors in the first months of life.  Objective: To determine the factors associated with hemoglobin levels in children under 6 months of age hospitalized in a specialized pediatric center in Peru. Methods: To determine the factors associated with hemoglobin levels in children under 6 months of age hospitalized in a specialized pediatric center in Peru. Results: 61.4% of the infants were women, and only 6.7% of the proportion of the studied population was less than 1 month old. 6.7% had a low birth weight, and 53.2% had a normal delivery. The level of anemia in hospitalized children under 6 months of age is 66.7%. Conclusions: The factors associated with hemoglobin levels were age, nutritional status, weight for length, and hospital causes. Likewise, an association was found between age and the median Hb in boys and girls aged 0 to 5 months.

Introducción: La anemia es una condición en la cual hay una baja concentración de los niveles de hemoglobina (Hb). Si bien se ha identificado muchas causas de la anemia, existen pocos estudios en los cuales se relacionan con factores epidemiológicos en los primeros meses de vida. Objetivo: Determinar los factores asociados a los niveles de hemoglobina en niños menores de 6 meses de edad hospitalizados en un centro pediátrico especializado de Perú. Métodos: Estudio analítico, transversal en niños menores de 6 meses de edad hospitalizados en los servicios de medicina de un centro pediátrico durante el año 2017, se revisaron 267 historias clínicas dándose énfasis en características clínicas y epidemiológicas. Resultados: El 61,4% de los lactantes eran mujeres, y solo un 6,7% de la proporción de la población estudiada presentaba menos de 1 mes. El 6,7% tuvieron baso peso al nacer, y el 53,2% tuvo un parto eutócico. El nivel de anemia en niños menores de 6 meses de edad hospitalizados es del 66,7%. Conclusion: Los factores asociados a los niveles de hemoglobina fueron  edad, estado nutricional de peso para la longitud y causas hospitalarias. Asimismo, se encontró asociación entre la edad con la mediana de Hb en los niños y niñas de 0 a 5 meses.

Prevalencia y factores de riesgo asociados a infección por virus SARS-CoV-2 en trabajadores del Instituto Nacional de Salud del Niño de Perú, abril 2020 a marzo 2021

Objetivo: Determinar la prevalencia y factores de riesgo asociados a la infección por virus SARS-CoV-2 en trabajadores del Instituto Nacional de Salud del Niño (INSN), en el periodo de abril 2020 a marzo 2021. Materiales y métodos: Estudio no experimental, descriptivo, transversal. La muestra corresponde a 608 trabajadores de salud que resultaron positivos a la prueba serológica rápida. Se revisaron las fichas de investigación clínica epidemiológica COVID-19 elaboradas por el Ministerio de Salud de Perú, que fueron autoadministradas por los trabajadores de salud, y el personal de Epidemiología del INSN verificó el llenado de la ficha. Los datos se introdujeron en una base de datos que sirvió para el análisis estadístico respectivo. El estudio fue aprobado por el Comité Institucional de Ética en Investigación del INSN (código de registro: PI-17/21). Resultados: La prevalencia fue de 7,24 % de COVID-19 en trabajadores del INSN entre abril del 2020 y marzo del 2021. El 71,4 % fueron mujeres, los participantes presentaron una media de edad de 44,71 años, mayoritariamente en el rango de los 30 a 59 años (83,4 %); el 65,6 % fueron asistenciales, de los cuales la mayoría fueron técnicos en enfermería. El 56,9 % de los trabajadores presentaron síntomas, principalmente fiebre/escalofríos (12,2 %), tos (8,9 %), malestar general (7,7 %), dolor de garganta (6,7 %), congestión nasal (2,5 %) y cefalea (1,3 %) . La mayoría de trabajadores residían en los distritos de Lima . Se encontró asociación significativa por sexo y grupos de edad, tipo de trabajador y perfil del trabajador. Conclusiones: La prevalencia de COVID-19 entre los trabajadores del INSN fue del 7,24 %; las características más frecuentes que mostraron diferencias significativas con el resto de los factores fueron el ser mujer, trabajador asistencial y técnica de enfermería. El 56,9 % de los trabajadores presentó síntomas, solo el 20,9 %, signos clínicos y el 10,9 % tuvo comorbilidades.

Objective: To determine the prevalence and risk factors associated with SARS-CoV-2 infection among workers of Instituto Nacional de Salud del Niño (INSN) from April 2020 to March 2021. Materials and methods: A non-experimental, descriptive, cross-sectional study. The sample consisted of 608 workers who tested positive for COVID-19 using a rapid antigen test. The COVID-19 clinical-epidemiological research sheets prepared by the Ministry of Health of Peru and self-administered by the workers were reviewed. The INSN Department of Epidemiology staff verified the completion of the sheets. The data was entered into a database, which was used for the respective statistical analysis. The study was approved by the INSN Institutional Research Ethics Committee (registration code: PI-17/21). Results: COVID-19 prevalence among INSN workers was 7.24 % from April 2020 to March 2021. Out of the workers with COVID-19, 71.4 % were women; 83.4 % were in the 30 to 59 age range with an average age of 44.71 years; 65.6 % were healthcare workers, most of whom were nursing technicians; and 56.9 % experienced symptoms, mainly fever/chills (12.2 %), cough (8.9 %), malaise (7.7 %), sore throat (6.7 %), stuffy nose (2.5 %) and headache (1.3 %). Most workers lived in Lima Centro districts (33.2 %). A significant association between sex, age groups, worker type and worker profile was found. Conclusions: COVID-19 prevalence among INSN workers was 7.24 %; the most frequent characteristics, which showed significant differences with the rest of the factors, were being a woman, healthcare worker and nursing technician. A total of 56.9 % of the workers experienced symptoms, only 20.9 % developed clinical signs and 10.9 % had comorbidities.

Dermatosis más frecuentes en pacientes con trasplante renal.

OBJECTIVE: To determine the most frequent dermatoses in patients with kidney transplant in the dermatology consultation, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, in Mexico City, in the period from March 2016 to March 2020. METHOD: Descriptive, cross-sectional study that included 153 patients with a complete medical history with prior informed consent and authorization from the hospital ethics committee. RESULTS: All patients presented one or more dermatoses. The most frequent were infectious (mycosis, viral) and, in decreasing order, other dermatoses (keratosis pilaris, melasma), tumorous (benign), inflammatory (seborrheic dermatitis, eczema), probably secondary to drugs and autoimmune (alopecia areata). CONCLUSIONS: All kidney transplant patients presented at least one dermatosis, predominantly those of infectious origin. We recommend dermatological evaluation prior to transplantation for timely diagnosis and treatment of dermatoses that could increase the morbi-mortality of patients.

OBJETIVO: Determinar las dermatosis más frecuentes en pacientes con trasplante renal en la consulta de dermatología del Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, en Ciudad de México, en el período de marzo de 2016 a marzo de 2020. MÉTODO: Estudio descriptivo, transversal que incluyó 153 pacientes con historia clínica completa, previo consentimiento informado y autorización del comité de ética del hospital. RESULTADOS: Todos los pacientes presentaron una o más dermatosis. Las más frecuentes fueron las infecciosas (micosis, virales) y, en orden decreciente, otras dermatosis (queratosis pilar, melasma), tumorales (benignas), inflamatorias (dermatitis seborreica, eccemas), probablemente secundarias a fármacos y autoinmunitarias (alopecia areata). CONCLUSIONES: Todos los pacientes receptores de trasplante renal presentaron al menos una dermatosis, predominando las de origen infeccioso. Recomendamos una valoración dermatológica previa al trasplante para el diagnóstico y el tratamiento oportuno de las dermatosis que podrían aumentar la morbimortalidad de los pacientes.

Maturation and Assembly of Iron-Sulfur Cluster-Containing Subunits in the Mitochondrial Complex I From Plants.

In plants, the mitochondrial complex I is the protein complex encompassing the largest number of iron-sulfur (Fe-S) clusters. The whole, membrane-embedded, holo-complex is assembled stepwise from assembly intermediates. The Q and N modules are combined to form a peripheral arm in the matrix, whereas the so-called membrane arm is formed after merging a carbonic anhydrase (CA) module with so-called Pp (proximal) and the Pd (distal) domains. A ferredoxin bridge connects both arms. The eight Fe-S clusters present in the peripheral arm for electron transfer reactions are synthesized via a dedicated protein machinery referred to as the iron-sulfur cluster (ISC) machinery. The de novo assembly occurs on ISCU scaffold proteins from iron, sulfur and electron delivery proteins. In a second step, the preformed Fe-S clusters are transferred, eventually converted and inserted in recipient apo-proteins. Diverse molecular actors, including a chaperone-cochaperone system, assembly factors among which proteins with LYR motifs, and Fe-S cluster carrier/transfer proteins, have been identified as contributors to the second step. This mini-review highlights the recent progresses in our understanding of how specificity is achieved during the delivery of preformed Fe-S clusters to complex I subunits.

NLRP3 Regulates IL-4 Expression in TOX+ CD4+ T Cells of Cutaneous T Cell Lymphoma to Potentially Promote Disease Progression.

In cutaneous T cell lymphoma (CTCL), a dominant Th2 profile associated with disease progression has been proposed. Moreover, although the production and regulation of IL-4 expression during the early stages of the disease may have important implications in later stages, these processes are poorly understood. Here, we demonstrate the presence of TOX+ CD4+ T cells that produce IL-4+ in early-stage skin lesions of CTCL patients and reveal a complex mechanism by which the NLRP3 receptor promotes a Th2 response by controlling IL-4 production. Unassembled NLRP3 is able to translocate to the nucleus of malignant CD4+ T cells, where it binds to the human il-4 promoter. Accordingly, IL-4 expression is decreased by knocking down and increased by promoting the nuclear localization of NLRP3. We describe a positive feedback loop in which IL-4 inhibits NLRP3 inflammasome assembly, thereby further increasing its production. IL-4 induced a potentially malignant phenotype measured based on TOX expression and proliferation. This mechanism of IL-4 regulation mediated by NLRP3 is amplified in late-stage CTCL associated with disease progression. These results indicate that NLRP3 might be a key regulator of IL-4 expression in TOX+ CD4+ T cells of CTCL patients and that this mechanism might have important implications in the progression of the disease.

Evaluación de alimentos procesados y ultraprocesados: Un análisis antes de la implementación del etiquetado frontal en Perú

RESUMEN Objetivo Evaluar los nutrientes críticos de alimentos industrializados y compararlos con los parámetros técnicos establecidos en la normatividad peruana, en sus dos etapas de implementación del etiquetado frontal en los empaques antes del inicio de su vigencia en junio de 2019. Métodos Estudio transversal en el que se analizaron los nutrientes críticos sodio, azúcar total, grasas saturadas y grasas trans de datos declarados en los etiquetados nutricionales de 511 alimentos procesados y ultraprocesados que formaron parte de los productos comprados para el consumo de 88 familias de estudiantes de una Universidad Privada de Lima. Los parámetros técnicos utilizados para evaluar los nutrientes críticos son los establecidos en el Reglamento de la Ley 30021. Todos los análisis se realizaron con Excel y SPSS versión 21, se utilizaron los estadísticos t de Student y Prueba de McNemar. Resultados Se analizaron 79 alimentos procesados y 432 alimentos ultraprocesados. Del total de los productos procesados y ultraprocesados evaluados, se encontró para el sodio que el 14.3% y 37.2% respectivamente superaran los parámetros en la primera y segunda etapa establecida en la normatividad; para el azúcar el 54.2% y el 62.6%; mientras que para las grasas saturadas el 52.8% y 59.5% respectivamente. Los alimentos tipo solidos son los que tendrán mayores cambios en el etiquetado frontal entre la primera y segunda etapa de implementación, a diferencia de los líquidos que sin cambiar la composición de sus productos su etiquetado frontal no variaría significativamente. Conclusiones La grasa saturada presente en los productos sólidos (procesados y ultraprocesados), sobrepasa los parámetros en ambas etapas de implementación en la mayoría de productos; del total de alimentos comparados independiente de su tipo y categoría, para la primera y segunda etapa de implementación, el nutriente crítico azúcar fue aquel que estuvo presente de manera elevada en la mayoría de los productos evaluados.

ABSTRACT Objective The objective of the current study was to evaluate critical nutrients of industrialized foods and compare them with the technical parameters established in the Peruvian regulations, in its two stages of implementation, referring to front-of-package labeling before the beginning of its validity in June 2019. Methods Cross-sectional study in which the critical nutrients of sodium, total sugar, saturated fat and transfat were analyzed from data declared in the nutritional labels of 511 processed and ultra-processed foods that were part of the products purchased for the consumption of 88 families of students from one private university in Lima. The technical parameters used to evaluate the critical nutrients are those established in the Regulation of Law 30021. All analyses were carried out with Excel and SPSS version 21, Student's t-statistics and McNemar's test were used. Results 79 processed foods and 432 ultra-processed foods were analyzed. Of the total processed and ultra-processed products evaluated, it was found that for sodium 14.3% and 37.2% respectively exceeded the parameters in the first and second stages established in the regulations; for sugar 54.2% and 62.6%; while for saturated fats 52.8% and 59.5%, respectively. Solid foods are those that will have the greatest changes in front labeling between the first and second stages of implementation, unlike liquids that without changing the composition of their products, their front labeling would not vary significantly. Conclusions The saturated fat present in solid products (processed and ultra-processed), exceeds the parameters in both stages of implementation in most products. Of the foods compared, regardless of type and category, the critical nutrient sugar was the one that was highly present in most of the products evaluated for the first and second stages of implementation.

Identification and Characterization of Novel Antioxidant Protein Hydrolysates from Kiwicha (Amaranthus caudatus L.).

Kiwicha (Amaranthus caudatus) is considered one of the few multipurpose pseudocereals for its potential use not only as a source of nutrients and fiber but also for its bioactive compounds. In recent years, antioxidant peptides are commonly used as functional ingredient of food. Herein, a kiwicha protein isolate (KPI), obtained from kiwicha defatted flour (KDF), was hydrolyzed by Bioprotease LA 660, a food-grade endoprotease, under specific conditions. The resulting kiwicha protein hydrolysates (KPHs) were chemically characterized and their digestibility and antioxidant capacity were evaluated by in vitro cell-free experiments owing to their measure of capacity to sequester DPPH free radical and reducing power. KPHs showed higher digestibility and antioxidant capacity than intact proteins into KPI. Therefore, the results shown in this study indicate that KPHs could serve as an adequate source of antioxidant peptides, representing an effective alternative to the generation of functional food.

Asociación entre percepción de consejos prácticos, mensajes educativos de las Guías Alimentarias y medios de difusión en universitarios peruanos / Association between perception of practical advice, educational messages of the Dietary Guidelines and the media in Peruvian university students

Determinar la asociación entre la percepción de los consejos prácticos y los mensajes educativos de las guías alimentarias en estudiantes de una universidad privada de Perú. Estudio transversal. La población correspondió a estudiantes que cursan el primero a décimo semestre de las carreras de una universidad privada de Lima-Perú. La muestra fue de 480 universitarios quienes aceptaron voluntariamente participar en el estudio. Los datos fueron recolectados en el periodo octubre a noviembre del año 2019. Se aplicó un cuestionario para recoger la percepción de estudiantes universitarios sobre los mensajes de las guías alimentarias y medios de difusión donde les gustaría conocer información sobre mensajes educativos. El 46,5% corresponde a estudiantes de las carreras de la Facultad de Ciencias de la Salud. Los mensajes 1, 3, 4, 6, 9 y 11 de las guías alimentarias peruanas mostraron asociación estadística evidente (p<0,05). Los medios de difusión con mayor proporción por los cuales les gustaría conocer mensajes educativos sobre alimentación saludable, fueron la Televisión (28,5%), Instagram (27,7%) y Facebook (19,0%). Se deberían diseñar e implementar publicidad diferenciada en televisión, Instagram y Facebook sobre alimentación saludable para contribuir a la mejora del estado de salud y nutrición de los universitarios peruanos(AU)

To determine the association between the perception of practical advice and the educational messages of the food guides in students of a private university in Peru. Cross-sectional study. The population corresponded to undergrads who are from the first to tenth semester of their degrees in a private university of Lima-Peru. The sample was 480 university students who voluntarily agreed to participate in the study. The data were collected in the period from october to november of the year 2019. A questionnaire was applied to collect the perception of university students about the messages of the dietary guidelines and the media where they would like to know information about educational messages. 46.5% correspond to undergrads of the Faculty of Health Sciences. Messages 1, 3, 4, 6, 9 and 11 of the Peruvian GABAS showed an evident statistical association (p <0.05). The media with the highest proportion by which they would like to know educational messages about healthy eating were Television (28.5%), Instagram (27.7%) and Facebook (19.0%). Differentiated advertising should be designed and implemented on television, Instagram and Facebook on healthy eating to contribute to the improvement of the health and nutrition status of Peruvian university students(AU)

Seeking an Initial-Weight-Independent Metric in a Mediterranean Cohort of Gastric Bypass Patients: the %AWL Revisited.

BACKGROUND: Most relative weight-loss metrics follow the formula "Weight loss(%) = 100 · (Initial BMI - Final BMI) / (Initial BMI-a)," where a is the reference point that defines the metric. The percentage of total weight loss (%TWL, a = 0) and percentage of excess weight loss (%EWL, a = 25) are influenced by a patient's initial weight. Recently, the percentage of alterable weight loss metric (%AWL, a = 13) has been reported to produce initial-weight-independent outcomes. OBJECTIVES: This study aimed to replicate the methodology used for %AWL determination in a Mediterranean cohort of bariatric patients. SETTINGS: Multicenter study in 10 large hospitals in Spain. METHODS: Two large prospective databases were retrospectively searched for all primary laparoscopic gastric bypass patients with 2 years of follow-up. Outcomes at nadir were expressed and analyzed with 26 different metrics (a from 0 to 25), looking for the metric whose outcomes produced (1) the lowest coefficient of variation, (2) no differences between initially lighter and heavier patients, and (3) no correlation with patients' initial BMI. RESULTS: A cohort of 1793 patients was stratified into 4 gender-age groups: younger women (YW, n = 733), older women (OW, n = 674), younger men (YM, n = 197), and older men (OM, n = 189). The calculations suggested an optimal reference point of 18 kg/m2, defining a new metric (percentage of Mediterranean alterable weight loss, %MAWL). When %TWL, %EWL, %AWL, and %MAWL were tested on the whole sample, only %MAWL produced initial-weight-independent results. CONCLUSIONS: In our Mediterranean cohort of patients, a reference point of 18 (and not 13) yielded initial-weight-independent outcomes.

Haploidentical transplantation in pediatric non-malignant diseases: A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation (GETH).

OBJECTIVE: Describe the GETH haploidentical stem cell transplantation (haplo-HSCT) activity in non-malignant disease (NMDs). METHODS: We retrospectively analyzed data from children with NMDs who underwent haplo-HSCT. RESULTS: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo-HSCT through ex vivo T cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) at 7 Spanish centers. Five cases employed unmanipulated PT-Cy haplo-HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+ CD19+ depletion, TCRαß+ CD19+ selection or naive CD45RA+ T-cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1-year cumulative incidence of graft failure was 27.4%. The 1-year III-IV acute graft-versus-host disease (GvHD) and 1-year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2-year overall survival was 44.9% for PIDs, and the 2-year graft-versus-host disease-free and relapse-free survival rate was 37.6% for the other NMDs. The transplantation-related mortality at day 100 was 30.8%. CONCLUSION: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.

Association of Pathogenic Th17 Cells with the Disease Severity and Its Potential Implication for Biological Treatment Selection in Psoriasis Patients.

Psoriasis is an inflammatory autoimmune disease characterized by cutaneous lesions in plaques. It has been proposed that the immune response has a key role in the disease progression. Particularly, the Th17 cells through IL-17 can contribute to maintain the inflammatory process. The pathogenic Th17 phenotype has been described in human diseases and associated with high severity in inflammatory experimental models. However, it is not clear if the pathogenic phenotype could be present in the skin and peripheral blood as well as its possible association to severity in psoriasis. In the lesional skin, we found high infiltration of Th17 cells and the pathogenic phenotype, finding a correlation between the frequency of Th17 cells and the Psoriasis Area and Severity Index (PASI) score. In peripheral blood, we observed a pool of Th17 lymphocytes with potential to acquire pathogenic features. Interestingly, the percentage of pathogenic Th17 cells (CD4+ RORγt+ IFN-γ +) correlates with disease severity. Moreover, we distinguished three groups of patients based on their IL-17/IFN-γ production by Th17 lymphocytes, which seems to be related with a dynamic or stable potential to express these cytokines. Remarkably, we evaluated the cytokine production by Th17 cells as an immunological marker for the adequate selection of biologic therapy. We found that patients analyzed by this immunological approach and treated with antibodies against IL-17 and TNFα showed great improvement depicted by reduction in PASI and Dermatology Life Quality Index (DLQI) score as well as the percentage of Body Surface Area (BSA). Altogether, our results highlight the importance of the assessment of the pathogenic phenotype in Th17 cells as an immune personalized analysis with the potential to support the therapy choice in the clinical practice.

Seasonal Variations in Macrophages/Microglia Underlie Changes in the Mouse Model of Multiple Sclerosis Severity.

Both immune and neurodegenerative mechanisms underlie multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). MS/EAE are triggered by encephalitogenic immune cells, including Th1 and Th17 cells, whereas T regulatory (Treg) cells are involved in inflammation resolution. Pro-inflammatory macrophages/microglia also play a deleterious role in the disease. Seasonal variations in MS relapses, active lesions, and pro- and anti-inflammatory cytokine levels have been described in MS patients and have been related with both perinatal and adult exposure to sunlight and other environmental factors. However, some data in EAE mice suggest that these variations might be, at least partially, endogenously determined. Thus, our objective was to study the effect of the season of birth and disease induction on the course of EAE, and immune cell infiltration in the central nervous system (CNS) in myelin oligodendrocyte glycoprotein (MOG35-55)-induced EAE in 8 weeks old, female C57BL/6N mice maintained under constant, controlled conditions. EAE severity as well as pathogenic (Th1, Th17, macrophages/microglia) and protective (Treg) subsets was found to vary according to the season of birth or of EAE induction. Summer-born or summer-immunized animals developed a milder disease, which coincided with variations in numbers of T effector/regulatory subsets, and significantly low numbers of macrophages/microglia. These results suggest that endogenous rhythms in immune responses might cause seasonal variations in EAE severity, and, maybe, in the course of MS, and that they might be related to macrophages/microglia.

Cintura hipertrigliceridémica en adultos pertenecientes al Policlínico Héroes del Moncada, en La Habana / Hypertriglyceridemic waist in adult patients belonging to Héroes del Moncada Polyclinic in Havana

Introducción: La hipertrigliceridemia es una forma de dislipidemia frecuentemente asociada con enfermedad ateroesclerótica. La obesidad se encuentra entre los factores de riesgo implicados en la aceleración del proceso ateroesclerótico. El desorden fisiopatológico provocado por el tejido adiposo disfuncionante es causa de afectaciones cardiovasculares, endocrinometabólicas y neoplásicas. Objetivo: Identificar la relación entre la presencia de hipertrigliceridemia con la circunferencia de la cintura en adultos mayores, a partir de la evaluación del índice de masa corporal, cintura-cadera y la presencia de hipertrigliceridemia, según la edad y el sexo. Métodos: Estudio descriptivo transversal realizado entre 2015-2017, con una muestra de 386 adultos de ambos sexos. La recogida de datos se realizó según el modelo de recolección del dato primario del Centro de Investigación y Referencias de Aterosclerosis de La Habana. El análisis de los datos se realizó con el programa SPSS v16- y las técnicas de Chi-Square. Resultados: La edad media de la muestra fue de 55,5 años y el 70,6 por ciento eran mujeres. El 57 por ciento presentaba hipertrigliceridemia y el 63,4 por ciento un índice de masa corporal aumentado, un 37,8 por ciento de personas con sobrepeso y un 26,5 por ciento con obesidad. El índice de masa corporal fue superior en mujeres perimenopáusicas, en las que tuvieron el predominio de cintura hipertrigliceridémica. Se observó un incremento de obesidad abdominal con la edad. Conclusiones: Los factores de riesgo cardiovascular, así como, la asociación existente entre los triglicéridos y la medida de la circunferencia de cintura, requiere una valoración sistemática por sexo y edad. La consulta de enfermería de la Atención Primaria es un lugar ideal para promover estrategias de intervención para monitorizar el riesgo clínico cardiovascular a través de los diferentes parámetros antropométricos(AU)

Introduction: Hypertriglyceridemia is a form of dyslipidemia frequently associated with the atherosclerotic disease. Obesity is among the risk factors involved in the acceleration of the atherosclerotic process. The pathophysiologic disorder caused by the dysfuncional adipose tissue is the cause of cardiovascular, endocrinometabolic and neoplastic diseases. Objective: To identify the relationship between the presence of hypertriglyceridemia and waist circumference in older adults from the assessment of the body mass index, waist-hip ratio and the presence of hypertriglyceridemia, according to age and gender. Methods: Descriptive, cross-sectional study conducted from 2015 to 2017, with a sample of 386 adults of both sexes. Data collection was performed according to the model of primary data collection of the Center for Research and of Atherosclerosis References of Havana. The data analysis was performed with the SPSS v16- software and the Chi-Square techniques. Results: The average age of the sample was 55.5 years and 70.6percent were women. The 57 percent had hypertriglyceridemia and 63.4 percent an increased body mass index; 37.8percent of the people had overweight and 26.5percent had obesity. Body mass index was higher in perimenopausal women, who had a predominance of hypertriglyceridemic waist. It was noticed an increase of the abdominal obesity with aging. Conclusions: The cardiovascular risk factors as well as the association between triglycerides and the measure of waist circumference require a systematic assessment by sex and age. The nursing consultation in Primary Care is an ideal place to promote intervention strategies to monitor the cardiovascular clinical risk through the different anthropometric parameters(AU)

Cintura hipertrigliceridémica en adultos pertenecientes al Policlínico Héroes del Moncada, en La Habana / Hypertriglyceridemic waist in adult patients belonging to Héroes del Moncada Polyclinic in Havana

Introducción: La hipertrigliceridemia es una forma de dislipidemia frecuentemente asociada con enfermedad ateroesclerótica. La obesidad se encuentra entre los factores de riesgo implicados en la aceleración del proceso ateroesclerótico. El desorden fisiopatológico provocado por el tejido adiposo disfuncionante es causa de afectaciones cardiovasculares, endocrinometabólicas y neoplásicas. Objetivo: Identificar la relación entre la presencia de hipertrigliceridemia con la circunferencia de la cintura en adultos mayores, a partir de la evaluación del índice de masa corporal, cintura-cadera y la presencia de hipertrigliceridemia, según la edad y el sexo. Métodos: Estudio descriptivo transversal realizado entre 2015-2017, con una muestra de 386 adultos de ambos sexos. La recogida de datos se realizó según el modelo de recolección del dato primario del Centro de Investigación y Referencias de Aterosclerosis de La Habana. El análisis de los datos se realizó con el programa SPSS v16- y las técnicas de Chi-Square. Resultados: La edad media de la muestra fue de 55,5 años y el 70,6 por ciento eran mujeres. El 57 por ciento presentaba hipertrigliceridemia y el 63,4 por ciento un índice de masa corporal aumentado, un 37,8 por ciento de personas con sobrepeso y un 26,5 por ciento con obesidad. El índice de masa corporal fue superior en mujeres perimenopáusicas, en las que tuvieron el predominio de cintura hipertrigliceridémica. Se observó un incremento de obesidad abdominal con la edad. Conclusiones: Los factores de riesgo cardiovascular, así como, la asociación existente entre los triglicéridos y la medida de la circunferencia de cintura, requiere una valoración sistemática por sexo y edad. La consulta de enfermería de la Atención Primaria es un lugar ideal para promover estrategias de intervención para monitorizar el riesgo clínico cardiovascular a través de los diferentes parámetros antropométricos(AU)

Introduction: Hypertriglyceridemia is a form of dyslipidemia frequently associated with the atherosclerotic disease. Obesity is among the risk factors involved in the acceleration of the atherosclerotic process. The pathophysiologic disorder caused by the dysfuncional adipose tissue is the cause of cardiovascular, endocrinometabolic and neoplastic diseases. Objective: To identify the relationship between the presence of hypertriglyceridemia and waist circumference in older adults from the assessment of the body mass index, waist-hip ratio and the presence of hypertriglyceridemia, according to age and gender. Methods: Descriptive, cross-sectional study conducted from 2015 to 2017, with a sample of 386 adults of both sexes. Data collection was performed according to the model of primary data collection of the Center for Research and of Atherosclerosis References of Havana. The data analysis was performed with the SPSS v16- software and the Chi-Square techniques. Results: The average age of the sample was 55.5 years and 70.6 percent were women. The 57 percent had hypertriglyceridemia and 63.4 percent an increased body mass index; 37.8 percent of the people had overweight and 26.5 percent had obesity. Body mass index was higher in perimenopausal women, who had a predominance of hypertriglyceridemic waist. It was noticed an increase of the abdominal obesity with aging. Conclusions: The cardiovascular risk factors as well as the association between triglycerides and the measure of waist circumference require a systematic assessment by sex and age. The nursing consultation in Primary Care is an ideal place to promote intervention strategies to monitor the cardiovascular clinical risk through the different anthropometric parameters(AU)

Haploidentical transplantation in high-risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH).

A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+ CD19+ depletion, TCRαß+ CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo-HSCT; bone marrow was the source in 9 of 41 patients following PT-CY haplo-HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer-cell immunoglobulin-like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease-free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo-HSCT were effective and could be utilized depending on the comfort level of the center.

Analysis of mid-term weight loss after Roux-en-Y gastric bypass and sleeve gastrectomy: Proposed percentile charts for total weight loss percentages to be used in daily clinical practice. / Análisis de la pérdida ponderal a medio plazo después del bypass gastroyeyunal en Y de Roux y de la gastrectomía vertical: propuesta de gráficos de percentiles del porcentaje de peso total perdido para su uso en la práctica clínica diaria.

INTRODUCTION: The aim of this study is to analyze weight evolution after the main bariatric surgical techniques (Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]) performed at a representative sample of Spanish hospitals in order to develop percentile charts for the percentage of total weight loss during the first 3 years after surgery. METHODS: A retrospective longitudinal cohort study was conducted based on the data provided by 9 Spanish hospitals. Weight data were analyzed both in % total weight loss and % excess weight lost corresponding to the RYGB (n=1,887) and SG (n=1,210). RESULTS: RYGB continues to be the most frequently performed technique in our sample. In both surgical techniques, maximum weight loss occurred 18 months after surgery. Both techniques followed the same weight evolution, although the % total weight loss values were lower in the case of the SG after 36 months (29.3±10 vs. 33.6±10). Age and gender are decisive in the weight results (better in younger patients for both techniques and better in women for RYGB). CONCLUSIONS: Percentile charts of % total weight loss after bariatric surgery represent a very useful tool and an important advance in the quality of patient management.