Incidence of intra-abdominal injuries in hemodynamically stable blunt trauma patients with a normal computed tomography scan admitted to the emergency department.

OBJECTIVES: Blunt abdominal trauma is a common cause of emergency department admission. Computed tomography (CT) scanning is the gold standard method for identifying intra-abdominal injuries in patients experiencing blunt trauma, especially those with high-energy trauma. Although the diagnostic accuracy of this imaging technique is very high, patient admission and prolonged observation protocols are still common practices worldwide. We aimed to evaluate the incidence of intra-abdominal injury in hemodynamically stable patients with high-energy blunt trauma and a normal abdominal CT scan at a Level-1 Trauma Center in Colombia, South America, to assess the relevance of a prolonged observation period. METHODS: We performed a retrospective study of patients admitted to the emergency department for blunt trauma between 2021 and 2022. All consecutive patients with high-energy mechanisms of trauma and a normal CT scan at admission were included. Our primary outcomes were the incidence of intra-abdominal injury identified during a 24-hour observation period or hospital stay, ICU admission, and death. RESULTS: We included 480 patients who met the inclusion criteria. The median age was 33 (IQR 25.5, 47), and 74.2% were male. The most common mechanisms of injury were motor vehicle accidents (64.2%), falls from height (26%), and falls from bikes (3.1%). A total of 99.2% of patients had a Revised Trauma Score of 8. Only 1 patient (0.2%) (95% CI: 0.01-1.16) presented with an abdominal injury during the observation period. No ICU admissions or deaths were reported. CONCLUSION: The incidence of intra-abdominal injury in patients with hemodynamically stable blunt trauma and a negative abdominal CT scan is extremely low, and prolonged observation may not be justified in these patients.

Dacriocistocele bilateral congénito: reporte de un caso / Congenital bilateral dacryocystocele: case report

Introducción: el dacriocistocele es una malformación congénita rara, secundaria a la obstrucción del conducto nasolagrimal; tiene una incidencia de 0,1 % de pacientes con obstrucción congénita del conducto nasolagrimal y se encuentra bilateralmente hasta en 25 % de casos. Caso clínico: lactante femenina de dos meses con celulitis periorbitaria derecha preseptal no asociada con lesión de entrada y diagnóstico inicial de dacriocistitis derecha. Al examen físico de ingreso, en el ojo derecho se evidencia gran masa abscedada en saco lagrimal; en el ojo izquierdo, un área indurada y leve reflujo a la presión del saco lagrimal. Se realiza tomografía computarizada de órbitas con hallazgos compatibles con dacriocistocele bilateral. Discusión y conclusiones: conocer la presentación y posibles complicaciones asociadas con esta patología previene una morbilidad importante al paciente. La mayoría de los casos de dacriocistocele se pueden manejar médicamente, sin embargo, aquellos asociados con complicaciones requieren de manejo quirúrgico oportuno.

Introduction: Dacryocystocele is a rare congenital malformation secondary to na-solacrimal duct obstruction. It has an incidence of 0.1% of patients with congenital nasolacrimal duct obstruction, being found bilaterally in up to 25% of cases. Case Report: Two-month-old female infant with preseptal right periorbital cellulitis not associated with an entrance lesion, with an initial diagnosis of right dacryocystitis. On physical examination, a large abscessed mass in the lacrimal sac was eviden-ced in the right eye; in the left eye, there was an indurated area and slight reflux to the lacrimal sac pressure. Computed tomography of the orbits was performed with findings compatible with bilateral dacryocystocele. Discussion and conclusions: Knowing the presentation and possible complications associated with this pathology prevents significant patient morbidity. Most cases of dacryocystocele can be mana-ged medically, however, cases associated with complications require timely surgical management.

Breast Cancer in Pregnant Young Women: Clinicopathological Profile, Survival, and Pregnancy Outcomes.

Background Breast cancer is one of the most common cancer types diagnosed during pregnancy; the presence of any neoplasm in pregnant women faces clinical dilemmas and challenges in cancer and pregnancy management. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within one year after delivery. The aim of this study was to describe tumor clinicopathological characteristics and pregnancy outcomes in PABC patients. Materials and methods This is a retrospective cohort assessing PABC patients. Qualitative variables were compared using Fisher's exact test. Kaplan-Meier method was used to calculate survival. Cox regression and logistic regression methods were used to estimate the hazard ratio (HR) and odds ratio (OR), respectively. Results We assessed 16 PABC patients. Women ≤ 35 years of age were mainly diagnosed at advanced stage (88.8%) with ER-negative disease (77.8%). Patients with >4 pathological lymph nodes (25%; p = 0.001) and ER-negative disease (50%; p = 0.646) showed poor five-year overall survival (OS). In the multivariate analysis, nodal involvement was the main predictor associated with poorer OS (HR = 1.4, 90% confidence interval [CI]: 1.14 to 1.8). The following risk factors might influence the risk of preterm delivery: maternal older age, gestational age at diagnosis, and intrauterine exposure to chemotherapy, but an adjusted OR of 0.61 (90% CI: 0.34 to 1), 0.80 (90% CI: 0.66 to 0.9), and 0.013 (90% CI: 0.00 to 0.9), respectively, did not statistically support such an effect. Conclusions Younger women with PABC had a more aggressive pathological profile that might partly explain the poor OS. Obstetrical adverse events related to preterm delivery should be avoided with better planning of specialized strategies.

No seroconversion among healthcare workers exposed to SARS-CoV-2 during the early phase of the pandemic.

BACKGROUND: The SARS-CoV-2 pandemic is associated with morbidity, hospitalizations, absenteeism, and mortality among healthcare workers (HCW). AIM: To evaluate the seroconversion rate in HCW exposed to SARS-CoV-2 in the early pandemic phase in 2020 at a regional reference hospital. MATERIAL AND METHODS: One hundred seventy-nine HCW working at a regional hospital were invited to a longitudinal study performed between April-July 2020. A serological analysis by ELISA IgG for viral nucleoprotein and protein S with a secondary analysis by ELISA IgG protein S1/S2 for samples with positive or doubtful result was carried out together with a complementary online survey to inquire about occupational or community exposures to SARS-CoV-2. RESULTS: Two cases with baseline infection were detected (1.1%, one symptomatic and one asymptomatic) and no cases of seroconversion were detected. During the study period, there were 136 patients hospitalized with COVID-19, and regional weekly COVID-19 incidence ranged from 2.7 to 24.4 per 100,000 inhabitants. No SARS-CoV-2 cases were detected by PCR among 27 HCW who consulted for respiratory symptoms in the period. Online surveys confirmed direct care of COVID-19 patients and also detected a high degree of unprotected social interaction at work. CONCLUSIONS: There was no evidence of seroconversion in this group of HCW exposed to the risk of infection by SARS-CoV-2 during the onset of the COVID-19 pandemic. Personal protective equipment and other measures used by the HCW were extremely useful for their protection in the initial phase of the pandemic.

Registro de síndromes coronarios agudos en centros de alta complejidad de Argentina. ReSCAR 2022 / Acute Coronary Syndromes in High Complexity Centers of Argentina. The ReSCAR Registry

RESUMEN Introducción : Realizamos un registro multicéntrico para analizar el abordaje diagnóstico y terapéutico de todos los tipos de síndromes coronarios agudos; este registro es el primero en abordar en detalle aquellos cuadros que cursan sin enfermedad coronaria epicárdica significativa. Es importante conocer la realidad del actual accionar médico con el objeto de hallar oportunidades de mejora. Material y métodos : Se registraron en forma prospectiva pacientes hospitalizados por síndrome coronario agudo en 15 centros de Argentina, con diagnóstico con troponina ultrasensible, servicio de unidad coronaria y hemodinamia disponible las 24 horas, entre enero y agosto de 2022. Resultados : Se incluyeron 984 pacientes consecutivos, un 22,2% con angina inestable, 39,1% con infarto agudo de miocardio sin elevación del segmento ST (IAMSEST) y 24,1% con infarto agudo de miocardio con elevación del segmento ST (IAMCEST). Por otro lado, el 4,1% se presentó como IAM tipo 2, 1,2% como miocarditis, 0,7% como síndrome de Takotsubo y 8,6% como infarto de miocardio con enfermedad coronaria no obstructiva (MINOCA). La mediana (rango intercuartílico, RIC) de edad fue de 66 años (56,5-74), con un 75,3% de pacientes de sexo masculino. El manejo inicial de los pacientes sin elevación del segmento ST fue invasivo en el 84%, con una tasa de enfermedad coronaria significativa del 76,5%. En cuanto a la evolución intrahospitalaria, las complicaciones isquémicas más relevantes fueron el reinfarto (2,84%), angina recurrente (2,4%), angina post infarto (2%) y trombosis intra stent (0,5%). El porcentaje de eventos hemorrágicos totales fue de 4,4% y la mortalidad intrahospitalaria total fue de 3,76%. Conclusiones : El registro tiene una buena representación del espectro de pacientes con sospecha inicial de síndrome coronario agudo, manejados en centros con una estrategia inicial principalmente invasiva, con una baja tasa de complicaciones hospitalarias y una mortalidad global aceptable.

ABSTRACT Background : We conducted a multicenter registry to analyze the diagnostic and therapeutic approach to all types of acute coronary syndromes; this registry is the first to provide detailed information on conditions without significant epicardial coronary artery disease. Knowing the reality of current medical practice is important to find opportunities for improvement. Methods : Patients hospitalized for acute coronary syndrome between January and August 2022 in 15 centers of Argentina, with high-sensitivity cardiac troponin, coronary care unit, and catheterization laboratory available 24 hours, were prospectively recorded. Results : A total of 984 consecutive patients were included, 22.2% with unstable angina, 39.1% with non-ST-segment elevation myocardial infarction (NSTEMI) and 24.1% with ST-segment elevation myocardial infarction (STEMI). Additionally, 4.1% presented as type 2 AMI, 1.2% as myocarditis, 0.7% as Takotsubo syndrome and 8.6% as myocardial infarction with non-obstructive coronary arteries (MINOCA). Median age was 66 years [interquartile range (IQR) 56.5-74] and 75.3% were men. An early invasive management was used in 84% of patients without ST segment elevation, and 76.5% of them had significant coronary artery disease. During hospitalization, 2.84% of the patients presented reinfarction, 2.43% recurrent angina, 2% postinfarction angina and 0.5% stent thrombosis. Bleeding events occurred in 4.4% of the patients, and overall in-hospital mortality was 3.76%. Conclusions : The registry has a good representation of the spectrum of patients with initial suspicion of "acute coronary syndrome", managed in centers with an invasive initial strategy and with low rate of in-hospital complications and acceptable overall mortality.

A single-step, rapid, and versatile method for simultaneous detection of cell surface glycan profiles using fluorochrome-conjugated lectins.

Cell surface glycans play essential roles in diverse physiological and pathological processes and their assessment has important implications in biomedicine and biotechnology. Here we present a rapid, versatile, and single-step multicolor flow cytometry method for evaluation of cell surface glycan signatures using a panel of selected fluorochrome-conjugated lectins. This procedure allows simultaneous detection of cell surface glycans with a 10-fold reduction in the number of cells required compared with traditional multistep lectin staining methods. Interestingly, we used this one-step lectin array coupled with dimension reduction algorithms in a proof-of-concept application for discrimination among different tumor and immune cell populations. Moreover, this procedure was also able to unveil T-, B-, and myeloid cell subclusters exhibiting differential glycophenotypes. Thus, we report a rapid and versatile lectin cytometry method to simultaneously detect a particular repertoire of surface glycans on living cells that can be easily implemented in different laboratories and core facilities.

Why do patients with antiphospholipid syndrome bleed? A clinical paradox.

Although worldwide-known criteria of antiphospholipid syndrome include thrombotic and obstetric events, a moderate number of patients manifest with bleeding episodes during course of the disease, which is typically attributed to the long-term anticoagulation. However, these haemorrhagic manifestations sometimes are part of pathophysiological changes that might occur secondary to the disease that involves endothelial activation, platelets dysfunction and blood clot factors misfunction. Recognizing these mechanisms of bleeding is crucial not only due to the need of treatment change or adding, but also because of changes in the disease' prognosis. In this review, we attempted to explain those complications, from its mechanism to a treatment approach, in order for physicians to be able to recognize patients with antiphospholipid syndrome and haemorrhagic manifestations, and to understand that, beyond over-anticoagulation, there are some other mechanisms that can trigger this complication and thus carry out a better diagnostic and therapeutic approach.

High-throughput screening method for discovering CatSper inhibitors using membrane depolarization caused by external calcium chelation and fluorescent cell barcoding.

The exclusive expression of CatSper in sperm and its critical role in sperm function makes this channel an attractive target for contraception. The strategy of blocking CatSper as a male, non-hormonal contraceptive has not been fully explored due to the lack of robust screening methods to discover novel and specific inhibitors. The reason for this lack of appropriate methodology is the structural and functional complexity of this channel. We have developed a high-throughput method to screen drugs with the capacity to block CatSper in mammalian sperm. The assay is based on removing external free divalent cations by chelation, inducing CatSper to efficiently conduct monovalent cations. Since Na+ is highly concentrated in the extracellular milieu, a sudden influx depolarizes the cell. Using CatSper1 KO sperm we demonstrated that this depolarization depends on CatSper function. A membrane potential (Em) assay was combined with fluorescent cell barcoding (FCB), enabling higher throughput flow cytometry based on unique fluorescent signatures of different sperm samples. These differentially labeled samples incubated in distinct experimental conditions can be combined into one tube for simultaneous acquisition. In this way, acquisition times are highly reduced, which is essential to perform larger screening experiments for drug discovery using live cells. Altogether, a simple strategy for assessing CatSper was validated, and this assay was used to develop a high-throughput drug screening for new CatSper blockers.

No seroconversion among healthcare workers exposed to SARS-CoV-2 during the early phase of the pandemic / Ausencia de seroconversión en trabajadores de la salud expuestos a SARS-CoV-2 durante la primera fase de la pandemia

BACKGROUND: The SARS-CoV-2 pandemic is associated with morbidity, hospitalizations, absenteeism, and mortality among healthcare workers (HCW). AIM: To evaluate the seroconversion rate in HCW exposed to SARS-CoV-2 in the early pandemic phase in 2020 at a regional reference hospital. MATERIAL AND METHODS: One hundred seventy-nine HCW working at a regional hospital were invited to a longitudinal study performed between April-July 2020. A serological analysis by ELISA IgG for viral nucleoprotein and protein S with a secondary analysis by ELISA IgG protein S1/S2 for samples with positive or doubtful result was carried out together with a complementary online survey to inquire about occupational or community exposures to SARS-CoV-2. RESULTS: Two cases with baseline infection were detected (1.1%, one symptomatic and one asymptomatic) and no cases of seroconversion were detected. During the study period, there were 136 patients hospitalized with COVID-19, and regional weekly COVID-19 incidence ranged from 2.7 to 24.4 per 100,000 inhabitants. No SARS-CoV-2 cases were detected by PCR among 27 HCW who consulted for respiratory symptoms in the period. Online surveys confirmed direct care of COVID-19 patients and also detected a high degree of unprotected social interaction at work. CONCLUSIONS: There was no evidence of seroconversion in this group of HCW exposed to the risk of infection by SARS-CoV-2 during the onset of the COVID-19 pandemic. Personal protective equipment and other measures used by the HCW were extremely useful for their protection in the initial phase of the pandemic.

ANTECEDENTES: La pandemia de SARS-CoV-2 está asociada a morbilidad, hospitalizaciones, ausentismo y mortalidad entre el personal de salud (PS). OBJETIVO: Evaluar la tasa de seroconversión en el PS expuesto al SARS-CoV-2 en la fase pandémica inicial el 2020 en un hospital regional de referencia. MATERIAL Y MÉTODOS: Ciento setenta y nueve trabajadores de la salud fueron invitados a un estudio longitudinal realizado entre abril-julio de 2020. Se efectuó un análisis serológico por ELISA IgG para nucleoproteína viral y proteína S con un análisis secundario por ELISA IgG proteína S1 / S2 para muestras con resultado positivo o dudoso junto a encuestas complementarias en línea para preguntar sobre exposiciones ocupacionales o comunitarias al SARS-CoV-2. RESULTADOS: Se detectaron dos casos con infección basal (1,1%, uno sintomático y uno asintomático) sin casos de seroconversión. Durante el período de estudio, hubo 136 pacientes hospitalizados con COVID-19, y la incidencia semanal regional de COVID-19 osciló entre 2,7 y 24,4 por 100.000 habitantes. No se detectaron casos de SARS-CoV-2 por PCR entre los 27 funcionarios que consultaron por síntomas respiratorios en este período. Las encuestas en línea confirmaron la atención directa de los pacientes con COVID-19 y también detectaron un alto grado de interacción social desprotegida en el trabajo. CONCLUSIONES: No hubo evidencia de seroconversión en un grupo de funcionarios expuestos al riesgo de infección por SARS-CoV-2 durante el inicio de la pandemia de COVID-19. Los equipos de protección personal y otras medidas utilizadas por el PS fueron de suma utilidad para su protección en la fase inicial de la pandemia.

Galectin-7 reprograms skin carcinogenesis by fostering innate immune evasive programs.

Non-melanoma skin cancer (NMSC) has risen dramatically as a result of chronic exposure to sunlight ultraviolet (UV) radiation, climatic changes and clinical conditions associated with immunosuppression. In spite of considerable progress, our understanding of the mechanisms that control NMSC development and their associated molecular and immunological landscapes is still limited. Here we demonstrated a critical role for galectin-7 (Gal-7), a ß-galactoside-binding protein preferentially expressed in skin tissue, during NMSC development. Transgenic mice (Tg46) overexpressing Gal-7 in keratinocytes showed higher number of papillomas compared to WT mice or mice lacking Gal-7 (Lgals7-/-) when subjected to a skin carcinogenesis protocol, in which tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were sequentially administered. RNAseq analysis of Tg46 tumor lesions revealed a unique profile compatible with cells of the myelomonocytic lineage infiltrating these tumors, an effect that was substantiated by a higher number of CD11b+Gr1+ cells in tumor-draining lymph nodes. Heightened c-Met activation and Cxcl-1 expression in Tg46 lesions suggested a contribution of this pathway to the recruitment of these cells. Remarkably, Gal-7 bound to the surface of CD11b+Ly6ChiLy6Glo monocytic myeloid cells and enhanced their immunosuppressive activity, as evidenced by increased IL-10 and TGF-ß1 secretion, and higher T-cell inhibitory activity. In vivo, carcinogen-treated Lgals7-/- animals adoptively transferred with Gal-7-conditioned monocytic myeloid cells developed higher number of papillomas, whereas depletion of these cells in Tg46-treated mice led to reduction in the number of tumors. Finally, human NMSC biopsies showed increased LGALS7 mRNA and Gal-7 protein expression and displayed transcriptional profiles associated with myeloid programs, accompanied by elevated CXCL1 expression and c-Met activation. Thus, Gal-7 emerges as a critical mediator of skin carcinogenesis and a potential therapeutic target in human NMSC.

[Associating prognostic factors with clinical results in locally advanced breast cancer]. / Asociando factores pronósticos con resultados clínicos en cáncer de mama localmente avanzado.

Background: Breast cancer is the most frequent malignant tumor in women. Objective: To identify clinico-pathological and molecular markers as predictors of survival in patients with locally advanced breast cancer (LABC). Methods: Retrospective and observational study. The clinical factors of clinico-pathological and molecular predictors in relation with overall survival (OS) were assessed by the survival function, baseline hazard with smoothing and Cox regression. Results: 126 patients were assessed. OS at five years was significantly superior in patients with clinical stage IIIA (87%; p < 0.001), grade 2 tumor (81%; p < 0.001), pathological node stage (ypN0: 90%; p < .001), low-risk Nottingham prognostic index (86%; p < 0.001) and luminal A subtype (88%; p = 0.022). Baseline hazard with smoothing exhibited an increase in the mortality rate at 50 months for the luminal B/ HER2+ subtype compared with other subtypes. The multivariate analysis ascertained that the stage ypN2-3 (hazard ratio [HR] = 7.3; 95% confidence interval [95% CI]: 2.2 to 23.9) and the HER2+ nonluminal (HR = 7.8; 95% CI: 2 to 29.6) and triple negative (HR = 5.4; 95% CI: 1.7 to 17.2) subtypes were associated with a poor OS. Conclusions: The comprehensive evaluation of the molecular marker and clinico-pathological factors provides more accurate predictive and prognostic information. The nodal stage and molecular subtype are suitable clinical parameters on survival for LABC patients.

Introducción: el cáncer de mama es el tumor maligno más frecuente en las mujeres. Objetivo: identificar marcadores clínico-patológicos y moleculares como predictores de la supervivencia en pacientes con cáncer de mama localmente avanzado (CMLA). Material y métodos: estudio retrospectivo y observacional. Los factores clínico-patológicos y moleculares fueron evaluados en relación con la supervivencia global (SG) mediante la función de supervivencia, riesgo basal con suavizamiento y regresión de Cox. Resultados: 126 pacientes fueron evaluadas. La SG a cinco años fue significativamente superior en pacientes con estadio clínico IIIA (87%; p < 0.001), tumor de grado 2 (81%; p < 0.001), ausencia de ganglios patológicos (ypN0: 90%; p < 0.001) y en el subtipo luminal A (88%; p = 0.022). El riesgo basal con suavizamiento exhibió un incremento en la tasa de mortalidad a los 50 meses para el subtipo luminal B/ HER2+ comparado con los otros subtipos. En el análisis multivariado, el estadio ypN2-3 (razón de riesgo [RR] = 7.3; intervalo de confianza del 95% [IC 95%]: 2.2 a 23.9) y los subtipos HER2+ (RR = 7.8; IC 95%: 2 a 29.6) y triple negativo (RR= 5.4; IC 95%: 1.7 a 17.2) se asociaron con una pobre SG. Conclusiones: la evaluación integral del marcador molecular y de los factores clínico-patológicos proporciona información predictiva y pronóstica más precisa. El estadio ganglionar y subtipo molecular son parámetros adecuados con un impacto pronóstico en la SG para las pacientes con CMLA.

[A functional platform to monitor SARS-CoV-2-specific T cell responses in vaccinated individuals and COVID-19 recovered patients]. / COVID-T: Una plataforma funcional para monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 en individuos vacunados y recuperados de COVID-19.

The rapid spread of the SARS-CoV-2, the causative agent of the emergent pandemic disease COVID-19, requires the urgent commitment of the immunology community to understand the adaptive immune response developed by COVID-19 convalescent patients and individuals vaccinated with different strategies and schemes, with the ultimate goal of implementing and optimizing health care and prevention policies. Currently, assessment of SARS-CoV-2-specific immunity is mainly focused on the measurement of the antibody titers and analysis of their neutralizing capacity. However, a considerable proportion of individuals lack humoral responses or show a progressive decline of SARS-CoV-2-specific neutralizing antibodies. In order to study the cellular response of convalescent patients and vaccinated individuals, we have developed the "COVID-T Platform", an optimized strategy to study SARS-CoV-2-specific T cell responses. This platform allows assessment of the nature, magnitude and persistence of antigen-specific T-cell immunity in COVID-19-convalescent patients and vaccinated individuals. Moreover, it gives the opportunity to study cellular responses against emerging coronavirus variants and to identify individuals with cross-reactive immunity against seasonal coronaviruses.

La rápida propagación del coronavirus SARS-CoV-2, agente causal de la enfermedad pandémica emergente COVID-19 y sus nuevas variantes, requiere del compromiso de la comunidad inmunológica para comprender la magnitud y naturaleza de la respuesta inmunológica adaptativa desarrollada por pacientes recuperados de COVID-19 e individuos vacunados con diferentes estrategias y protocolos, a los fines de implementar nuevas políticas sanitarias. En la actualidad, la determinación de la inmunidad contra SARS-CoV-2 se basa principalmente en la detección de anticuerpos específicos y la determinación de su actividad neutralizante. Sin embargo, a pesar de la alta sensibilidad de estos ensayos, un número considerable de pacientes e individuos vacunados carecen de respuesta humoral detectable, o evidencian una disminución rápida de la misma en el tiempo. Con el objetivo de estudiar la respuesta inmune celular desencadenada frente a SARS-CoV-2, en nuestro laboratorio desarrollamos la "Plataforma COVID-T" estrategia integral optimizada dirigida a caracterizar y monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 a partir de muestras de sangre de individuos vacunados y/o recuperados de COVID-19. Esta plataforma permite evaluar la naturaleza, magnitud y persistencia de la inmunidad celular T generada tanto por la infección con SARS-CoV-2, como por distintos esquemas y protocolos de vacunación en diferentes poblaciones de individuos. Asimismo, permite evaluar la respuesta inmunológica T generada frente a nuevas variantes del virus e identificar individuos sanos resistentes a SARS-CoV-2 con inmunidad pre-existente hacia coronavirus estacionales.

Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation.

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.

COVID-T: una plataforma funcional para monitorear la respuesta de linfocitos t específicos de SARS-COV-2 en individuos vacunados y recuperados de COVID-19 / COVID-T: A functional platform to monitor SARS-CoV-2-specific T cell responses in vaccinated individuals and COVID-19 recovered patients

Resumen La rápida propagación del coronavirus SARS-CoV-2, agente causal de la enfermedad pandémica emergente COVID-19 y sus nuevas variantes, requiere del compromiso de la comunidad inmunológica para comprender la magnitud y naturaleza de la respuesta inmunológica adaptativa desarrollada por pacientes recuperados de COVID-19 e individuos vacunados con diferentes estrategias y protocolos, a los fines de imple mentar nuevas políticas sanitarias. En la actualidad, la determinación de la inmunidad contra SARS-CoV-2 se basa principalmente en la detección de anticuerpos específicos y la determinación de su actividad neutralizante. Sin embargo, a pesar de la alta sensibilidad de estos ensayos, un número considerable de pacientes e indivi duos vacunados carecen de respuesta humoral detectable, o evidencian una disminución rápida de la misma en el tiempo. Con el objetivo de estudiar la respuesta inmune celular desencadenada frente a SARS-CoV-2, en nuestro laboratorio desarrollamos la "Plataforma COVID-T" estrategia integral optimizada dirigida a caracte rizar y monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 a partir de muestras de sangre de individuos vacunados y/o recuperados de COVID-19. Esta plataforma permite evaluar la naturaleza, magnitud y persistencia de la inmunidad celular T generada tanto por la infección con SARS-CoV-2, como por distintos esquemas y protocolos de vacunación en diferentes poblaciones de individuos. Asimismo, permite evaluar la respuesta inmunológica T generada frente a nuevas variantes del virus e identificar individuos sanos resistentes a SARS-CoV-2 con inmunidad pre-existente hacia coronavirus estacionales.

Abstract The rapid spread of the SARS-CoV-2, the caus ative agent of the emergent pandemic disease COVID-19, requires the urgent commitment of the immunology community to understand the adaptive immune response developed by COVID-19 convalescent patients and individuals vaccinated with different strategies and schemes, with the ultimate goal of implementing and optimizing health care and prevention policies. Currently, assessment of SARS-CoV-2-specific immunity is mainly focused on the measurement of the antibody titers and analysis of their neutralizing capacity. However, a considerable proportion of individuals lack humoral responses or show a progressive decline of SARS-CoV-2-specific neutral izing antibodies. In order to study the cellular response of convalescent patients and vaccinated individuals, we have developed the 'COVID-T Platform', an optimized strategy to study SARS-CoV-2-specific T cell responses. This platform allows assessment of the nature, magnitude and persistence of antigen-specific T-cell immunity in COVID-19-convalescent patients and vaccinated individuals. Moreover, it gives the opportunity to study cellular responses against emerging coronavirus variants and to identify individuals with cross-reactive immunity against seasonal coronaviruses.

Explicit and implicit markers of fairness preeminence in criminal judges.

Achieving justice could be considered a complex social decision-making scenario. Despite the relevance of social decisions for legal contexts, these processes have still not been explored for individuals who work as criminal judges dispensing justice. To bridge the gap, we used a complex social decision-making task (Ultimatum game) and tracked a heart rate variability measurement: the square root of the mean squared differences of successive NN intervals (RMSSD) at their baseline (as an implicit measurement that tracks emotion regulation behavior) for criminal judges (n = 24) and a control group (n = 27). Our results revealed that, compared to controls, judges were slower and rejected a bigger proportion of unfair offers. Moreover, the rate of rejections and the reaction times were predicted by higher RMSSD scores for the judges. This study provides evidence about the impact of legal background and expertise in complex social decision-making. Our results contribute to understanding how expertise can shape criminal judges' social behaviors and pave the way for promising new research into the cognitive and physiological factors associated with social decision-making.

Fibrilación auricular de novo en pacientes con síndrome coronario agudo sin elevación del segmento ST. Datos del Registro Buenos Aires I / De Novo Atrial Fibrillation in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome. Data from the Buenos Aires I Registry

RESUMEN Introducción: La fibrilación auricular (FA) es la arritmia con mayor incidencia a nivel mundial y tiene una clara asociación con los síndromes coronarios agudos. El propósito de nuestro trabajo es describir la incidencia, los factores predisponentes y el pronóstico de pacientes con FA de novo luego de un síndrome coronario agudo, en una población representativa de nuestro medio. Material y métodos: Se realizó un subanálisis del registro BUENOS AIRES I, el cual incluyó 1110 pacientes con síndrome coronario agudo sin elevación del ST (SCASEST), con un seguimiento a 6 meses. Resultados: Se evidenció una incidencia del 7,7% de FA de novo y se identificaron como factores predictores independientes de su desarrollo la edad (OR 1,04; IC95% 1,02-1,08; p = 0,001), la presentación inicial con infarto agudo de miocardio (OR 2,35; IC95% 1,20-4,57; p = 0,012) y la necesidad de revascularización quirúrgica (OR 6,86; IC95% 3,95-11,89; p <0,001). Los pacientes que desarrollaron FA presentaron mayor mortalidad por todas las causas, mayor mortalidad cardiovascular y eventos de sangrado BARC ≥2. Se identificó a la FA de novo post-SCASEST como un factor predictor independiente de mortalidad cardiovascular (OR 3,67; IC95% 1,25-10,76; p = 0,018) y sangrado a 6 meses BARC ≥2 (OR 3,024; IC95% 1,49-6,11; p = 0,002). Conclusiones: Este subanálisis preespecificado del registro BUENOS AIRES I demostró una incidencia significativa de FA de novo en el contexto de un SCASEST, vinculada a una mayor edad, mayor daño estructural cardíaco agudo y requerimiento de cirugía de revascularización, y con una peor evolución en términos de eventos clínicos adversos en el seguimiento a mediano plazo.

ABSTRACT Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and has a close correlation with acute coronary syndromes. The aim of our study is to describe the incidence, predisposing factors and outcome of patients with de novo AF after an acute coronary syndrome in a population representative of our environment. Methods: We conducted a sub-analysis of the BUENOS AIRES I registry, which included 1110 patients with non- ST-segment elevation acute coronary syndrome (NSTE-ACS) followed-up at 6 months. Results: The incidence of de novo AF was 7.7%. The independent predictors of de novo AF were age (OR, 1.04; 95% CI, 1.021.08; p = 0.001), initial presentation as MI (OR, 2.35; 95% CI, 1.20-4.57; p = 0.012) and requirement of myocardial revascularization surgery (OR 6.86; 95% CI 3.95-11.89; p < 0.001). Patients who developed AF had greater all-cause mortality, cardiovascular mortality and bleeding events ≥BARC type 2. The development of de novo AF after NSTE-ACS was identified as an independent predictor of cardiovascular mortality (OR, 3.67; 95% CI 1.25-10.76; p = 0.018) and of bleeding events ≥ BARC type 2 (OR, 3.024; 95% CI, 1.49-6.11; p = 0.002). Conclusions: This prespecified sub-analysis of the BUENOS AIRES I registry demonstrated a significant incidence of de novo AF in the setting of a NSTE-ACS, associated with elderly patients, greater acute myocardial structural damage and need for myocardial revascularization surgery, with worse outcome in terms of adverse clinical events at mid-term follow-up.

Circulating and Tumor-Infiltrating NK Cells From Clear Cell Renal Cell Carcinoma Patients Exhibit a Predominantly Inhibitory Phenotype Characterized by Overexpression of CD85j, CD45, CD48 and PD-1.

Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.

Equipos de trauma: realidad mundial e implementación en un país en desarrollo. Descripción narrativa / Trauma teams: global reality and implementation in a developing country. Narrative description

Introducción. El trauma es una de las entidades con mayor morbimortalidad en el mundo. Los equipos especializados en la atención del paciente traumatizado son llamados «equipos de trauma¼. Dichos equipos surgieron de la necesidad de brindar tratamiento oportuno multidisciplinario a individuos con heridas que condicionan gran severidad en la guerra; sin embargo, con el paso del tiempo se trasladaron al ámbito civil, generando un impacto positivo en términos de tiempos de atención, mortalidad y morbilidad. El objetivo de este estudio fue describir el proceso de desarrollo de los equipos de trauma a nivel mundial y la experiencia en nuestra institución en el suroccidente colombiano. Métodos. Se realizó una búsqueda en la base de datos PUBMED, que incluyó revisiones sistemáticas, metaanálisis, revisiones de Cochrane, ensayos clínicos y series de casos. Resultados. Se incluyeron 41 estudios para esta revisión narrativa, y se observó que el tiempo de permanencia en Emergencias, el tiempo de traslado a cirugía, la mortalidad y las complicaciones asociadas al trauma fueron menores cuando se implementan equipos de trauma. Discusión. El diseño de un sistema de atención y valoración horizontal de un paciente con traumatismos severos produce un impacto positivo en términos de tiempos de atención, mortalidad y morbilidad. Se hace necesario establecer los parámetros operativos necesarios en las instituciones de salud de alta y mediana complejidad en nuestro país para implementar dichos equipos de trabajo

Introduction. Trauma is one of the entities with the highest morbidity and mortality in the world. Teams specialized in trauma patient care are called «trauma teams¼. These teams arose from the need to provide timely multidisciplinary treatment to individuals with severe injuries in war; however, with time they moved to the civilian arena, generating a positive impact in terms of care times, mortality and morbidity. The objective of this study was to describe the process of development of trauma teams worldwide and the experience in our institution in southwestern Colombia. Methods. A search of the PUBMED database was carried out, which included systematic reviews, metaanalyses, Cochrane reviews, clinical trials, and case series.Results. Forty-one studies were included for this narrative review, and it was observed that the length of stay in the ER, the time of transfer to surgery, mortality and complications associated with trauma were lower when trauma teams are implemented. Discussion. The design of a horizontal care and assessment system for a patient with severe trauma produces a positive impact in terms of care times, mortality and morbidity. It is necessary to establish operational parameters in high and medium complexity health institutions in our country to implement such work teams