Influence of lymphopenia on long-term mortality in septic shock, a retrospective observational study.

BACKGROUND AND OBJECTIVE: The diagnosis of infection, to diagnose septic shock, has been qualified by leukocyte counts and protein biomarkers. Septic shock mortality is persistently high (20%-50%), and rising in the long term. The definition of sepsis does not include leukocyte count, and lymphopenia has been associated with its mortality in the short term. Immunosuppression and increased mortality in the long term due to sepsis have not been demonstrated. The aim is to relate the occurrence of lymphopenia and its lack of recovery during septic shock with mortality at 2 years. PATIENTS AND METHODS: Cohort of 332 elderly patients diagnosed with septic shock. Mortality at 28 days and 2 years was analysed according to leukocyte, neutrophil, and lymphocyte counts, and the ability to recover from lymphopenia (LRec). RESULTS: A total of 74.1% of patients showed lymphopenia, and 73.5% did not improve during ICU stay. Mortality was 31.0% and 50.3% at 28 days and 2 years, respectively. Lymphopenia was a predictor of early mortality (OR 2.96) and LRec of late mortality (OR 3.98). Long-term mortality was associated with LRec (HR 1.69). CONCLUSIONS: In elderly patients with septic shock, 28-day mortality is associated with lymphopenia and neutrophilia, and LRec with 2-year mortality; this may represent 2 distinct phenotypes of behaviour after septic shock.

SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis. / Infección por SARS-CoV-2 y seroprevalencia en pacientes con esclerosis múltiple.

INTRODUCTION: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease. METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined. RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed. CONCLUSIONS: The incidence of COVID-19 was slightly lower in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.

SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis.

INTRODUCTION: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease. METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined. RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed. CONCLUSIONS: The incidence of COVID-19 was slightly higher in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.

Linfocitopenia como biomarcador de gravedad en pacientes pediátricos con la COVID-19

Introducción: La COVID-19 en edades pediátricas presenta características singulares; un pequeño número de pacientes pediátricos desarrollan un estado clínico grave. Objetivos: Evaluar si la linfocitopenia es un predictor de gravedad en pacientes pediátricos con la COVID-19. Métodos: Se estudiaron en 706 pacientes, las variables edad, sexo, antecedentes patológicos personales de enfermedades crónicas de la infancia (asma bronquial, diabetes mellitus), comorbilidades, estado clínico, valores de linfocitos, conteo absoluto de linfocitos (≤ 1 x 109/L = linfocitopenia). De acuerdo con el estado clínico los pacientes se agruparon en 5 grupos, de asintomáticos a críticos. Se determinó la correlación entre el estado clínico y el conteo absoluto de linfocitos; de este se determinó su capacidad discriminativa para estimar el pronóstico. Resultados: La media de la edad fue 8,6 años; el 6,2 % de los pacientes evolucionó al estado grave o crítico; 74,6 % tuvo valores normales de linfocitos, el 16,14 % altos y el 9,2 % bajos. Linfocitopenia presentó el 4,2 %; se correlacionó significativamente con estado grave, área bajo la curva de 0,711 (IC 95 %: 0,595-0,827); 46 % de sensibilidad y 98 % de especificidad. Conclusiones: La linfocitopenia es un biomarcador que puede estimar el pronóstico en pacientes pediátricos con la COVID-19 que desarrollan un estado clínico grave.

Introduction: COVID-19 in pediatric ages presents unique features; a small number of pediatric patients develop severe clinical status. Objectives: To evaluate whether lymphocytopenia is a predictor of severity in pediatric patients with COVID-19. Methods: In 706 patients were studied the variables age, sex, personal pathological history of childhood chronic diseases (bronchial asthma, diabetes mellitus), comorbidities, clinical status, lymphocyte values, absolute lymphocyte count (≤ 1 x 109/L = lymphocytopenia). According to clinical status patients were grouped into 5 groups, from asymptomatic to critical. The correlation between clinical status and absolute lymphocyte count was determined; its discriminative capacity to estimate prognosis was determined. Results: The mean age was 8.6 years; 6.2% of patients progressed to severe or critical condition; 74.6% had normal lymphocyte values, 16.14% high and 9.2% low. Lymphocytopenia presented 4.2%; it was significantly correlated with severe condition, area under the curve of 0.711 (95% CI: 0.595-0.827); 46% sensitivity and 98% specificity. Conclusions: Lymphocytopenia is a biomarker that can estimate prognosis in pediatric patients with COVID-19 who develop severe clinical status.

Síndrome inflamatorio multisistémico en pediatría: importancia de la evaluación inicial de los parámetros de laboratorio / Multisystem Inflammatory Syndrome in children: the importance of evaluation of early laboratory parameters

RESUMEN Introducción : El síndrome inflamatorio multisistémico en pediatría (SIM-C) es una infrecuente entidad asociada a COVID-19 con un amplio espectro de presentación: desde un cuadro similar a la enfermedad de Kawasaki a una afectación multisistémica con shock. Se han descripto asociaciones entre valores de laboratorio y mala evolución, pero no existen puntos de corte que predigan la misma. Objetivo : El objetivo de este estudio fue describir y analizar las características de los pacientes con SIM-C y las relaciones de estas con los hallazgos de laboratorio. Material y métodos : Se realizó un estudio analítico y retrospectivo de niños internados con diagnóstico de SIM-C entre mayo 2020 y junio 2021 en el HNRG. Se estudiaron 32 pacientes, 17 femeninas (53,13%) y 15 masculinos (46,87%), edad promedio de 7,67 años (rango 0,5-14,91). Diez de los pacientes (31,25%) presentaron shock. Se obtuvieron datos clínicos, ecocardiográficos y valores de troponina I ultrasensible, NT-proBNP, plaquetas y linfocitos al momento del diagnóstico; y se analizaron comparativamente entre quienes presentaron shock durante la evolución (Grupo 1) y quienes no (Grupo 2). Resultados : La diferencia en un valor inicial de NT-proBNP elevado fue estadísticamente significativa entre ambos grupos (p=0,008), en tanto que la troponina y el recuento de linfocitos y plaquetas, no. De los 13 pacientes que requirieron inotrópicos, el 58% presentó linfopenia inicialmente (p=0,006 vs aquellos que no los necesitaron). Conclusiones : Si bien la mortalidad debido al SIM-C es baja, la afectación cardiovascular y el compromiso hemodinámico en los paci entes que presentaron este síndrome puede ser frecuente. Poder contar con una herramienta de laboratorio ampliamente difundida para la categorización de pacientes podría ayudar a mitigar riesgos y obtener una derivación temprana a centros especializados.

ABSTRACT Background : Multisystem inflammatory syndrome in children (MIS-C) is an uncommon condition associated with COVID-19 with a wide spectrum of presentations, ranging from Kawasaki-like disease to multisystem involvement with shock. The as sociation between the laboratory characteristics and unfavorable outcome has been described, but the cut-off points associated with higher risk have not yet been defined. Objective : The aim of this study was to describe and analyze the characteristics of patients with MIS-C and their associations with the laboratory findings. Methods : We conducted an analytical and retrospective study of pediatric patients hospitalized between May 2020 and June 2021 with diagnosis of MIS-C in Hospital General de Niños Dr. Ricardo Gutiérrez (HNRG). The cohort was made up of 23 patients, 17 female (53.13%) and 15 male (46.87%); mean age was 7.67 years (range 0.5-14.91). Ten patients (31.25%) presented shock. Clinical and echocardiographic data and values of high-sensitive troponin I, N-terminal pro-B-type natriuretic peptide (NT-proBNP), platelets and lymphocytes at the time of diagnosis were obtained and compared between those with shock during evolution (group 1) and those without shock (group 2). Results : There was a significant difference in baseline elevated NT-proBNP values between both groups (p = 0.008), but not in troponin levels and lymphocyte and platelet counts. Of the 13 patients who required inotropic agents, 58% had baseline lymphopenia (p = 0.006 vs those who did not require inotropic drugs). Conclusions : Although mortality due to MIS-C is low, cardiac involvement and hemodynamic impairment may be common. The availability of a commonly used laboratory tool for patient categorization could help to mitigate risks and obtain early referral to specialized centers.

Asociación entre la variación de glóbulos blancos y las manifestaciones clínicas, anticuerpos e infecciones en adultos con lupus eritematoso sistémico / White blood cells count variation in systemic lupus erythematosus: its association to disease manifestations, antibodies and risk of infections

Introducción: la asociación de leucopenia, linfopenia y neutropenia con la presencia de autoanticuerpos, manifestaciones clínicas e infecciones en pacientes con lupus eritematoso sistémico (LES) no está bien establecida. Los objetivos de este estudio fueron analizar los cambios en los recuentos de leucocitos y linfocitos en pacientes con LES y su asociación con manifestaciones clínicas, autoanticuerpos y riesgo de infecciones. Materiales y métodos: se recolectaron retrospectivamente los valores de leucocitos, linfocitos y neutrófilos. Se agruparon a los pacientes en cinco categorías: recuento de glóbulos blancos normales, leucopenia (persistente o intermitente) y linfopenia (persistente o intermitente). Se registraron las manifestaciones clínicas, los autoanticuerpos acumulados, el daño, la mortalidad, las infecciones y los tratamientos inmunosupresores recibidos de cada paciente. Resultados: se incluyeron 89 pacientes. La linfopenia (89%) fue la anormalidad más frecuente. La leucopenia intermitente y la persistente se detectaron en el 44% y en el 11% de los pacientes, respectivamente. La linfopenia intermitente y la persistente se hallaron en el 44% y en el 45% de los casos. En el análisis univariado, la presencia de rash discoide se asoció a leucopenia (20,4 vs. 5,1; p=0,059) y el tratamiento con mofetil micofenolato a un recuento normal de leucocitos (p=0,046). El compromiso neurológico se asoció a recuento normal de linfocitos (22,2% vs. 0% y 7,5%; p=0,027); los pacientes con anti-RNP (anti ribonucleoproteína nuclear) presentaron más frecuentemente linfopenia persistente (47% vs. 15,4% y 20%; p=0,007). Ninguno de los grupos se asoció a una mayor prevalencia de infecciones. En el análisis multivariado, el mofetil micofenolato se asoció negativamente a leucopenia (OR 0.33 IC 95% 0,1-0,9; p=0,042) y el compromiso neurológico se asoció negativamente a linfopenia (OR 0.08; p=0,022). Conclusiones: en el análisis univariado, el rash discoide se asoció a leucopenia y el anti-RNP a linfopenia. Al ajustar por otras variables significativas, el tratamiento con mofetil micofenolato se asoció a un recuento normal de leucocitos, mientras que las manifestaciones neurológicas se relacionaron a linfocitos normales. No se demostró asociación de las infecciones con ninguno de los grupos.

Introduction: leukopenia, lymphopenia and neutropenia association to clinical manifestations and infections in systemic lupus erythematosus (SLE) is not well defined. The objectives were to analize leucocytes and lymphocytes variations in SLE patients and their association to clinical manifestations, autoantibodies and infections risk. Materials and methods: total white blood cell (WBC) count, lymphocyte, and neutrophils counts were collected retrospectively. Data were grouped into normal WBC cell count, persistent or intermittent leucopenia and lymphopenia. Disease manifestations, accumulated autoantibodies, damage, mortality, infections and immunosuppressants ever received were registered. Results: study sample included 89 patients. Lymphopenia (89%) was the most common abnormality. Intermittent and persistent leukopenia were detected in 44% and 11% cases. Intermittent and persistent lymphopenia were found in 44% and 45% cases. In univariate analysis, discoid rash was associated to leukopenia (20.4 vs 5.1 p=0.059) and mycophenolate treatment to normal leukocyte count (p=0.046). Patients with neurological disorder tended to have normal lymphocyte counts rather than intermittent or persistent lymphopenia (22.2% vs 0% and 7.5% p=0.027); patients with anti-RNP tended to belong to the persistent lymphopenia group (47% vs 15.4% and 20% p=0.007). Infections were not associated to any of the categories. In multivariate analysis mycophenolate was negatively associated to leukopenia (OR 0.33 95% CI 0.1-0.9 p=0.042) while neurological disorder was negatively associated to lymphopenia (OR 0.08 p=0.022). Conclusions: in univariate analysis, discoid rash was associated to leukopenia and anti-RNP to lymphopenia. When adjusted to other significant variables, mycophenolate was related to normal leukocyte while neurological manifestations were to normal lymphocyte counts. Infections were not associated to any of the categories.

Síndrome inflamatorio multisistémico pediátrico (SIMS) asociado con el SARS-CoV-2: Un estudio de cohorte retrospectivo / SARS-CoV-2-associated pediatric multisystemic inflammatory syndrome: A retrospective cohort study

Introduccion: El Síndrome inflamatorio multisistémico pediátrico (SIMS) asociado con el SARS-CoV-2 es una enfermedad aguda acompañada de un síndrome hiperinflamatorio, con falla multiorgánica y shock, asociada a la infección por SARS CoV2, que produce alta morbilidad en la población pediátrica, que hasta el momento es la afectada por este síndrome. Objetivo: Evaluar las características diferenciales del síndrome multisistémico inflamatorio asociado al SARS-COV-2 (SIMS) en niños. Métodos: se realizó un estudio de cohorte retrospectivo. La definición de SIMS se basó en los criterios de la OMS. Los pacientes con COVID-19 relacionados temporalmente se incluyeron como controles. Resultados: se incluyeron 25 pacientes con SIMS y 75 controles. El modelo de regresión logística múltiple de las variables que mostraron ser significativas en el análisis univariado reveló que la edad ≥ 2 años (OR 24,7; IC del 95%: 1,03 -592,4; P = 0,048), la linfopenia (OR 9,03; IC del 95%: 2,05-39,7; P = 0,004), y el recuento de plaquetas <150x109 / L (OR 11,7; IC del 95%: 1,88-75,22; P = 0,009) se asociaron significativamente con SIMS. La presencia de una enfermedad subyacente pareció reducir el riesgo de SIMS (OR 0,06; IC del 95%: 0,01-0,3). Conclusión: El SIMS fue más común en pacientes mayores de 2 años y en aquellos con linfopenia o trombocitopenia. La enfermedad subyacente parece reducir el riesgo del mismo. (AU)

Introduction: SARS-CoV-2-associated pediatric multisystemic inflammatory syndrome (PMIS) is an acute disease accompanied by a hyperinflammatory syndrome, with multiorgan failure and shock associated with SARS CoV2 infection, producing high morbidity in the pediatric population, which so far is affected by this syndrome. Objective: To evaluate the differential characteristics of SARS-COV-2-associated PMIS in children. Methods: A retrospective cohort study was conducted. The definition of PMIS was based on WHO criteria. Patients with temporally related COVID-19 were included as controls. Results: 25 patients with PMIS and 75 controls were included. A multiple logistic regression model of the variables shown to be significant in univariate analysis revealed that age ≥ 2 years (OR 24.7; 95% CI: 1.03 -592.4; P = 0.048), lymphopenia (OR 9.03; 95% CI 2.05-39.7; P = 0.004), and platelet count < 150x109/L (OR 11.7; 95% CI: 1.88-75.22; P = 0.009) were significantly associated with PMIS. The presence of an underlying disease appeared to reduce the risk of PMIS (OR 0.06; 95% CI: 0.01-0.3). Conclusion: PMIS was more common in patients older than 2 years and in those with lymphopenia or thrombocytopenia. Underlying disease appears to reduce the risk of SMIS.(AU)

Anormalidades hematológicas en pacientes con el SARS-CoV-2 (COVID-19) y sus implicaciones pronósticas / Hematological abnormalities in patients with the SARS-CoV-2 (COVID-19) and its prognostic implications

Resumen La infección por coronavirus 2 del síndrome respiratorio agudo grave condiciona un gran número de anormalidades pulmonares y sistémicas que basan su fisiopatogenia en la inmunotrombosis. Específicamente para el área de la hematología desde los primeros estudios de caracterización clínica y paraclínica se identificaron anormalidades hematológicas y de la hemostasia que se han documentado de forma consistente en diferentes publicaciones y cuyo conocimiento es trascendente desde el punto de vista de pronóstico. Durante el curso de la enfermedad, la evaluación longitudinal de algunos parámetros hematológicos es primordial para la identificación temprana de pacientes potencialmente complicables. El conteo absoluto de leucocitos, la depleción linfoide y la trombocitopenia son los marcadores hematológicos principalmente alterados. La linfopenia severa es un hallazgo cardinal en la fase temprana de la infección y su persistencia durante la progresión de la enfermedad tiene mayor impacto pronóstico adverso. La determinación de los índices hemáticos neutrófilo:linfocito y linfocito:plaqueta también ha demostrado su utilidad como predictores de complicaciones respiratorias y mortalidad. Un estado de hipercoagulabilidad demostrado por niveles altos de dímero D y/o productos de degradación de fibrinógeno y diversas alteraciones hemostásicas en el perfil de coagulación se asocian a una mayor tasa de morbimortalidad. Otros biomarcadores inflamatorios, incluidos proteína C reactiva, procalcitonina y ferritina, podrían identificar tempranamente aquellos casos que requieren de soporte ventilatorio y/o hemodinámico avanzado. En esta revisión se abordan los antecedentes históricos de la patología y las principales alteraciones hematológicas y de la hemostasia y sus implicaciones pronósticas.

Abstract Severe acute respiratory syndrome coronavirus 2 infection conditions a large number of pulmonary and systemic abnormalities that base its physiopathogenesis on immunothrombosis. Specifically, for the area of hematology, from the first clinical and paraclinical characterization studies, hematological and hemostasis abnormalities have been identified that have been consistently documented through different publications and whose knowledge is transcendent from the prognostic point of view. During the course of the disease, longitudinal evaluation of some hematological parameters is essential for the early identification of potentially complicated patients. Absolute leukocyte count, lymphoid depletion, and thrombocytopenia are the principally altered hematologic markers. Severe lymphopenia is a cardinal finding in the early phase of infection, and its persistence during disease progression has a greater adverse prognostic impact. The determination of the neutrophil/ lymphocyte and lymphocyte/ platelet hematic indices have also shown their usefulness as predictors of respiratory complications and mortality. A state of hypercoagulability demonstrated by high levels of D-dimer and or fibrinogen degradation products and various hemostatic alterations in the coagulation profile are associated with a higher rate of morbidity and mortality. Other inflammatory biomarkers including C-Reactive Protein, procalcitonin and ferritin can early identify those cases that require advanced ventilatory and/or hemodynamic support. In this review, the historical antecedents of the pathology and the main hematological and hemostasis alterations and their prognostic implications are addressed.

¿Cómo sospechar en el primer nivel de atención pacientes con errores innatos de la inmunidad? / How to suspect patients with innate immunity errors at the first level of care?

Actualmente existen 430 inmunodeficiencias primarias (IDP) también denominadas errores innatos de la inmunidad, resultado de más de 320 mutaciones identificadas, que en conjunto afectan al menos a 1 de cada 500 recién nacidos vivos, por lo que ya no son consideradas como enfermedades raras. Muchos médicos no sospechan estas patologías, lo cual genera retraso en el diagnóstico y tratamiento, generando un mal pronóstico de calidad de vida y muerte; por lo cual el objetivo de este artículo es transmitir los puntos clave para su sospecha y referencia a un centro de atención especializado. (AU)

Currently there are 430 primary immunodeficiencies (PIDs) also called innate immunity errors, resulting from more than 320 identified mutations, which together affect at least 1 in 500 live newborns and are therefore no longer considered rare diseases. Many doctors do not suspect these pathologies, which generates delay in diagnosis and treatment, generating a poor prognosis for life quality and death, for which reason the objective of this article is to transmit the key points for their suspicion and reference to a specialized center.

Clinical, hematological and risk factors associated with borreliosis in horses from Sao Paulo, Brazil / Fatores clínicos, hematológicos e de risco associados à borreliose em cavalos de São Paulo, Brasil

Lyme borreliosis is caused by Borrelia burgdorferi sensu lato and affects humans and many other mammals, including horses. This disease is poorly studied and reported in horses, and epidemiological surveys are required to provide more precise information about the course of the disease. The aims of the present study were to determine the prevalence of seropositive horses for Borrelia burgdorferi sensu lato in São Paulo State, Brazil and to collect data on possible risk factors associated with the disease along with clinical and hematological changes in seropositive horses. There was verified that there was a high correlation between the occurrence of seropositive horses infested with Amblyomma sculptum ticks and the presence of capybaras on the property as well as the occurrence of abortion and retained placenta in mares. In terms of hematological alterations, the occurrence of lymphopenia was observed in seropositive animals. Borreliosis in horses from São Paulo, Brazil can be associated with presence of Amblyomma scupltum ticks, proximity with capybaras and can be manifested as alterations in reproduction of mares and lymphopenia.(AU)

A borreliose de Lyme é causada por Borrelia burgdorferi sensu lato e afeta humanos e muitos outros mamíferos, incluindo cavalos. Esta doença é pouco estudada e relatada em equinos, sendo necessários levantamentos epidemiológicos para fornecer informações mais precisas sobre o curso da doença. Os objetivos do presente estudo foram determinar a prevalência de cavalos soropositivos para Borrelia burgdorferi sensu lato no Estado de São Paulo, Brasil e coletar dados sobre possíveis fatores de risco associados à doença, juntamente com alterações clínicas e hematológicas em cavalos soropositivos. Verificou-se que houve alta correlação entre a ocorrência de equinos soropositivos infestados por carrapatos Amblyomma sculptum e a presença de capivaras nas propriedades, bem como a ocorrência de abortamento e retenção de placenta em éguas. Em termos de alterações hematológicas, observou-se a ocorrência de linfopenia em animais soropositivos. A borreliose em cavalos de São Paulo, Brasil, pode estar associada à presença de carrapatos Amblyomma scupltum, proximidade com capivaras e se manifestar clinicamente como alterações reprodutivas em éguas e linfopenia.(AU)

Clinical, hematological and risk factors associated with borreliosis in horses from Sao Paulo, Brazil / Fatores clínicos, hematológicos e de risco associados à borreliose em cavalos de São Paulo, Brasil

Lyme borreliosis is caused by Borrelia burgdorferi sensu lato and affects humans and many other mammals, including horses. This disease is poorly studied and reported in horses, and epidemiological surveys are required to provide more precise information about the course of the disease. The aims of the present study were to determine the prevalence of seropositive horses for Borrelia burgdorferi sensu lato in São Paulo State, Brazil and to collect data on possible risk factors associated with the disease along with clinical and hematological changes in seropositive horses. There was verified that there was a high correlation between the occurrence of seropositive horses infested with Amblyomma sculptum ticks and the presence of capybaras on the property as well as the occurrence of abortion and retained placenta in mares. In terms of hematological alterations, the occurrence of lymphopenia was observed in seropositive animals. Borreliosis in horses from São Paulo, Brazil can be associated with presence of Amblyomma scupltum ticks, proximity with capybaras and can be manifested as alterations in reproduction of mares and lymphopenia.

A borreliose de Lyme é causada por Borrelia burgdorferi sensu lato e afeta humanos e muitos outros mamíferos, incluindo cavalos. Esta doença é pouco estudada e relatada em equinos, sendo necessários levantamentos epidemiológicos para fornecer informações mais precisas sobre o curso da doença. Os objetivos do presente estudo foram determinar a prevalência de cavalos soropositivos para Borrelia burgdorferi sensu lato no Estado de São Paulo, Brasil e coletar dados sobre possíveis fatores de risco associados à doença, juntamente com alterações clínicas e hematológicas em cavalos soropositivos. Verificou-se que houve alta correlação entre a ocorrência de equinos soropositivos infestados por carrapatos Amblyomma sculptum e a presença de capivaras nas propriedades, bem como a ocorrência de abortamento e retenção de placenta em éguas. Em termos de alterações hematológicas, observou-se a ocorrência de linfopenia em animais soropositivos. A borreliose em cavalos de São Paulo, Brasil, pode estar associada à presença de carrapatos Amblyomma scupltum, proximidade com capivaras e se manifestar clinicamente como alterações reprodutivas em éguas e linfopenia.

Seguridad y persistencia del dimetilfumarato como tratamiento para la esclerosis múltiple remitente-recurrente / Safety and persistence of dimethyl fumarate as a treatment for relapsing-remitting multiple-sclerosis

Objetivo: Dimetilfumarato es un fármaco autorizado en el tratamientode la esclerosis múltiple recurrente-remitente. El objetivo es evaluar laseguridad y persistencia del dimetilfumarato en la práctica clínica, y analizar la evolución de las linfopenias en pacientes en tratamiento con dimetilfumarato un mínimo de 6 meses.Método: Estudio observacional, longitudinal, retrospectivo entre agostode 2015 y marzo de 2019. Se incluyeron todos los pacientes en tratamiento durante un periodo mínimo de 6 meses. Se recogieron los datosde recuento linfocitario a diferentes tiempos: pretratamiento, a los 3, 6,12 meses y al final del periodo de estudio. Como modelo estadístico seutilizó la regresión logística para analizar la evolución de las linfopenias.Se estudió la relación entre el descenso del recuento linfocitario los primeros 6 meses de tratamiento y el desarrollo a tiempo final del estudio delinfopenias grado II/III que podrían ser motivo de suspensión. Además, seevaluaron otros indicadores de seguridad: reacciones adversas, suspensiones y abandonos de tratamiento. Para el análisis de la persistencia secontabilizaron los meses transcurridos desde el inicio hasta la suspensióndel tratamiento.Resultados: Se incluyeron 55 pacientes. El 80% fueron mujeres. Lasreacciones adversas más frecuentes fueron: linfopenia (27), rubefacción(16), molestias digestivas (11), fatiga (9), cefalea (3) y alteraciones delsueño (2). Durante el periodo considerado hubo 11 abandonos/suspensiones de tratamiento, las razones fueron: embarazo (2), decisión propia(2), infección por virus John Cunningham (1), alergia al fármaco (2) ylinfopenia (4). La mediana de duración de tratamiento fue de 23 meses(4-43 meses). (AU)

Objective: Dimethyl fumarate is a medication approved for the treatmentof relapsing-remitting multiple sclerosis. The purpose of the study was toevaluate the safety and persistence of dimethyl fumarate in clinical practice and analyze the occurrence of lymphopenia is patients treated withdimethyl fumarate over a period of at least 6 months.Method: This is a retrospective longitudinal observational study carriedout between August 2015 and March 2019. The study cohort was madeup of patients who had been treated with dimethyl fumarate for at least6 months. Lymphocyte counts were recorded at different points of time(pre-treatment, at 3, 6, 12 months, and at the end of the study period). Theevolution of lymphopenia was evaluated by means of a logistic regressionstatistical model. An analysis was performed of the relationship betweena decreased lymphocyte count over the first 6 months of treatment andthe development, by the end of the study, of grade II-III lymphopenianecessitating discontinuation of dimethyl fumarate. Other safety indicatorswere also evaluated including adverse events and interruptions or discontinuations of treatment. Persistence was determined by measuring the timeto discontinuation of treatment.Results: The study included a total of 55 patients, of whom 80% werefemale. The most common adverse events were lymphopenia (27), rubefaction (16), digestive symptoms (11), fatigue (9), headache (3) and sleepdisturbances (2). Eleven subjects interrupted/discontinued their treatment during the study period; reasons were as follows: pregnancy (2), personal decision (2), John Cunningham virus infection (1), allergy to the drug(2), and lymphopenia (4). Median duration of treatment was 23 months(4-43 months). A statistically significant association was found betweena lower lymphocyte count over the first 6 months of treatment and thedevelopment of severe lymphopenia by the end of the study [OR = 1.34(1.27-11.41); 95% CI (p = 0.001)]. )(AU)

Infección por SARS-CoV-2 y seroprevalencia en pacientes con esclerosis múltiple / SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis

Introducción: El efecto de la infección por SARS-CoV-2 en los pacientes con esclerosis múltiple (EM) y la influencia de los tratamientos modificadores de la enfermedad (TME) es desconocida. Hasta el momento no se ha observado que los pacientes con EM tengan mayor riesgo de infección por COVID-19, ni peor curso evolutivo de la misma.MétodosEstudio descriptivo de pacientes con EM e infección por SARS-CoV-2 diagnosticada mediante PCR. Hemos analizado variables demográficas, clínicas, de laboratorio y de tratamiento en nuestra muestra. Se ha determinado la presencia de anticuerpos frente a SARS-CoV-2 en estos pacientes.ResultadosLa forma de esclerosis múltiple remitente recurrente (EMRR) fue la más frecuente en lo pacientes con EM e infección por COVID-19. El 10,2% presentó una evolución desfavorable, relacionada con una mayor edad y una Expanded Disability Status Scale (EDSS) más elevada. La seroprevalencia de anticuerpos frente a SARS-CoV-2 en nuestro estudio ha sido del 83,3%. El desarrollo de anticuerpos no está relacionado con el TME, la presencia de linfopenia u otros factores analizados.ConclusionesLa incidencia de COVID-19 ha sido ligeramente inferior a la de la población general de nuestra provincia. La evolución desfavorable se ha relacionado con una mayor edad y una puntuación elevada en la EDSS. El TME y la linfopenia no se han relacionado con el curso de la infección por COVID-19. La seroprevalencia es similar a la encontrada en población general con PCR positiva, sin poder determinar la influencia de los distintos TME. (AU)

Introduction: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease.MethodsWe performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined.ResultsRelapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed.ConclusionsThe incidence of COVID-19 was slightly lower in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined. (AU)

COVID-19: fisiopatología e inmunopatología / Physiopathology and immunopathology of COVID-19: narrative review

La fisiopatología y la inmunopatología del COVID-19 están íntimamente relacionadas entre sí y son dependientes la una de la otra. La complejidad de ambos procesos puede desencadenar daños multiorgánicos, producto de la toxicidad viral directa (la cual es dependiente de la expresión del receptor de enzima convertidora de angiotensina 2 o ACE2), del daño de las células endoteliales y tromboinflamación (induciendo endotelitis en múltiples lechos vasculares), y de la desregulación de la respuesta inmune y del sistema reninaangiotensina-aldosterona (SRAA), lo que se traduce en efectos citopáticos virales con daños en órganos diana. La enfermedad se caracteriza por presentar reacciones hiperinflamatorias que pueden desencadenar una liberación exacerbada de citoquinas proinflamatorias, proceso denominado "tormenta de citoquinas". La desregulación de la respuesta inmune produce linfopenia (de los linfocitos T CD4,+ CD8+, y B) así como un aumento de la relación neutrófilos-linfocitos. También se evidencia un claro incremento de marcadores inflamatorios, como los reactantes de fase aguda(AU)

The physiopathology and immunopathology of COVID-19 are both related and dependent on each other, The complexity of both processes has the potential to unfold multi-organ failure, product of the endothelium inflammation in multiple vascular beds, also viral toxicity (which depends, as well, on the expression of the angiotensin-converting enzyme 2 or ACE2), the damage on endothelial cells and thrombo-inflammation (inducing a dysregulation of the immune response and the renin-angiotensin-aldosterone system (RAAS), with cytopathic viral effects and damage on target organs. This disease also presents hyperinflammatory reactions that can lead to the exacerbated release of proinflammatory cytokines, a process known as "cytokine storm". The dysregulation of the immune response also generates lymphopenia, and a higher ratio of the neutrophils-lymphocytes ratio. There is a clear increase of the inflammatory markers, including the acute phase reactants. The understanding of the physiopathology and immunopathology is crucial in order to comprehend the bases of COVID-19, its treatment and prevention(AU)

Criptococosis meníngea en un paciente con linfopenia T-CD4+ idiopática / Cryptococcal meningitis in a patient with idiopathic CD4+ T lymphopenia

RESUMEN La infección por el virus de la inmunodeficiencia humana es el factor de riesgo principal para desarrollar criptococosis meníngea; sin embargo, existe una entidad poco conocida, la linfopenia T-CD4+ idiopática, que genera un inexplicable déficit de células T-CD4+ circulantes predisponiendo a variadas complicaciones, entre ellas la infección por gérmenes oportunistas. Presentamos el caso de un paciente con criptococosis meníngea secundaria a una linfopenia T-CD4+ idiopática, que a nuestro conocimiento es el primer caso reportado en el Perú. Esta enfermedad debería considerarse en pacientes negativos para el virus de inmunodeficiencia humana, que cursen con infecciones infrecuentes del sistema nervioso central, ya que la evolución, manejo y pronóstico podrían ser distintos en pacientes con esta condición.

ABSTRACT Infection with the human immunodeficiency virus (HIV) is the main risk factor for developing cryptococcal meningitis. However, there is a poorly known entity, idiopathic CD4+ T-cell lymphopenia, which leads to an unexplainable CD4+ circulating T-cell deficit, predisposing patients to many complications, including infections caused by opportunistic microorganisms. We present the case of a patient with cryptococcal meningitis secondary to idiopathic T-CD4+ lymphopenia, which, as far as we know, is the very first case of its kind reported in Peru. This entity should be considered in patients negative for HIV infection developing non-common infections of the central nervous system, since outcome, management, and prognosis may be different in patients with this condition.

Linfopenia y riesgo de infecciones nosocomiales en ancianos en una institución de salud de Bogotá, Colombia. Estudio de casos y controles / Lymphopenia and risk of nosocomial infections in elderly in a health institution of Bogotá, Colombia. Cases and controls study

Resumen Objetivo: La linfopenia se ha propuesto como un potencial factor asociado al riesgo de infecciones bacterianas nosocomiales (infección urinaria y neumonía), pero la magnitud y relevancia de este factor no ha sido evaluada formalmente. El objetivo de este estudio es determinar si existe asociación entre linfopenia e infecciones nosocomiales en ancianos hospitalizados en una institución de salud en Bogotá, Colombia. Métodos: Estudio de casos y controles, incluyendo personas mayores de 65 años hospitalizadas en el Hospital Universitario San Ignacio entre junio de 2016 y diciembre de 2017. Se consideraron casos aquellos con diagnóstico de infección nosocomial (neumonía, infección de vías urinarias, bacteriemia, infección de tejidos blandos) y se compararon con controles sin infección emparejados por edad y sexo. Se evaluó la asociación entre linfopenia e infección nosocomial mediante análisis bivariado y multivariado controlando por las variables de confusión. Resultados: Se incluyeron un total de 198 pacientes (99 casos y 99 controles). La prevalencia de linfopenia fue de 34.8%, sin encontrarse diferencia entre los dos grupos (p=0.88). La infección nosocomial se asoció a mayor incidencia de mortalidad (29.3 vs 10.1%, p>0.001) y mayor duración de estancia hospitalaria (Mediana 18 vs 9 días, p<0.01). Se encontró asociación entre infección nosocomial con enfermedad cardiovascular (OR = 2.87; IC 95% 1.37-6.00) y antecedente de cáncer (OR = 6.00; IC 95% 1.28-29.78), sin embargo, no hubo asociación con linfopenia (OR = 1.27; IC 95% 0.61-2.65). Conclusiones: Este estudio sugiere que no existe asociación entre linfopenia y el desarrollo de infecciones nosocomiales en pacientes ancianos.

Abstract Objective: Lymphopenia has been proposed as a potential factor associated with the risk of nosocomial bacterial infections (urinary tract infection and pneumonia), but the magnitude and relevance of this factor has not been formally evaluated. Objective is to determine the association between lymphopenia and nosocomial infections in elderly hospitalized in a health institution in Bogotá, Colombia. Methods: Case-control study, including people over 65 hospitalized in the University Hospital San Ignacio - Bogotá, during the period between June 2016 and December 2017. Cases with a diagnosis of nosocomial infection (pneumonia, urinary tract infection, bacteraemia, soft tissue infection) were considered and compared with controls without infection matched by age and sex. The association between lymphopenia and nosocomial infection was evaluated by bivariate and multivariate analysis, controlling for confounding variables. Results: A total of 198 patients (99 cases and 99 controls) were included. The prevalence of lymphopenia was 34.8%, with no difference between the two groups (p = 0.88). Nosocomial infection was associated with a higher incidence of mortality (29.3 vs. 10.1%, p> 0.001) and a longer duration of hospital stay (Median 18 vs. 9 days, p< 0.001). An association was found between nosocomial infection with cardiovascular disease (OR = 2.87; 95% CI 1.37-6.00) and a history of cancer (OR = 6.19; 95% CI 1.28-29.78), however, there was no association with lymphopenia (OR = 1.27 ; 95% CI 0.61-2.65). Conclusions: This study suggests that there is no association between lymphopenia and the development of nosocomial infections in elderly patients.

Alteraciones hematológicas en COVID-19 / Hematological Findings in COVID-19

Resumen El SARS (síndrome respiratorio agudo grave) es el estadio grave de la COVID-19 ocasionado por el SARS-CoV-2, que causa infecciones respiratorias en humanos y cuya transmisión se da principalmente por contacto. El virus ingresa a la célula huésped por la interacción de la proteína S con la enzima convertidora de angiotensina II (ACE2), presente en el tracto respiratorio, así como en monocitos, macrófagos, células endoteliales, corazón y tracto gastrointestinal. El aumento de IFN frena la replicación viral y activa la respuesta inmune adaptativa. Así, las manifestaciones clínicas de la infección se presentan frecuentemente a nivel del tracto respiratorio; sin embargo, también pueden involucrar otros sistemas como el hematopoyético. En el hemograma se observan recuentos celulares alterados, principalmente leucocitos y plaquetas. La linfopenia y neutrofilia se asocian con enfermedad severa y la trombocitopenia se presenta de manera heterogénea en la infección. Entre las complicaciones se encuentra la coagulación intravascular diseminada, producida cuando los monocitos y las células endoteliales son activadas por la liberación de citoquinas; esto genera daño endotelial, con la síntesis del factor tisular, secreción de factor tisular, activación plaquetaria y liberación del factor Von Willebrand, así como una condición hiperfibrinolítica especialmente en estadios tardíos de la infección. Las pruebas de laboratorio como el dímero D, los productos de degradación de la fibrina (PDF), tiempo de protrombina (TP), tiempo de tromboplastina parcial activado (TTPA), entre otras, son fundamentales para el diagnóstico, seguimiento y pronóstico de la enfermedad.

Abstract Severe Acute Respiratory Syndrome (SARS) is the serious condition of coronavirus (COVID-19) caused by SARS-COV-2 which causes respiratory infections in humans, and whose transmission is given mainly through the contact. this virus enters into the host cell due to the spike protein (S) interaction with the angiotensin-converting enzyme 2 (ACE2), which is not only present in the respiratory tract but also monocytes, macrophages, endothelial cells, the heart, and gastrointestinal tract. The increase in INF stops viral replication and activates the adaptive immune response. The infection's clinic manifestations often occur in the respiratory tract; however, other systems like the hematopoietic may be affected. Altered cell counts, mainly leukocytes and platelets, are seen on the blood count. Lymphopenia and neutrophilia are associated with severe disease; thrombocytopenia is present in a heterogeneous way in the infection. Among the disease's complications are the Disseminated Intravascular Coagulation (DIC) that results when monocytes and endothelial cells are activated because of the release of cytokines, causing endothelial damage, with the synthesis of the tissue factor, tissue factor discharge, platelet activation, and the von Willebrand factor release, generating a hyperfibrinolytic condition especially in the infection's late-stage. Laboratory tests such as D-dimer (D-D), Fibrinogen Degradation Products (FDP), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) among others, are essential to the diagnosis, monitoring, and prognosis of the disease.

El papel de la paradoja de la obesidad y el conteo linfocitario en sepsis / The role of the obesity paradox and lymphocytic count on sepsis / O papel do paradoxo da obesidade e contagem de linfócitos na sepse

Resumen: Introducción: La obesidad es un factor protector para mortalidad en la sepsis, a este fenómeno se le conoce como «paradoja de la obesidad¼. La obesidad es un estado inflamatorio crónico, que incluye mediadores de la inmunidad innata y adaptativa. Un marcador de inmunidad adaptativa es la linfopenia, ésta es relacionada con peor evolución y mayor mortalidad. Objetivo: Determinar la relación del índice de masa corporal (IMC) con conteo linfocitario y su relación con supervivencia en pacientes sépticos. Material y métodos: Estudio de cohortes, retrospectivo, en pacientes con sepsis y/o choque séptico mayores de 18 años, sin enfermedades autoinmunes, ni tratamiento inmunosupresor, determinando IMC y linfopenia. Resultados: Se incluyeron 206 pacientes, 8.7% con peso bajo, 46.6% peso normal, 24.8% con sobrepeso, 19.9% con obesidad. El grupo de mayor mortalidad con linfopenia tuvo los menores valores de IMC 21.37 kg/m2. El análisis de supervivencia reveló que un IMC < 22.5 kg/m2 y linfopenia son factores de riesgo independientes para mortalidad. Conclusiones: La obesidad se relaciona con mayor conteo linfocitario y mayor supervivencia en sepsis y choque séptico, por lo que el IMC y el conteo linfocitario son factores independientes para mortalidad estadísticamente significativos, proponemos la escala APACHE II ajustada con estas variables.

Abstract: Introduction: Obesity is a mortality protector factor in sepsis; this phenomenon is known as «obesity paradox¼. Furthermore, obesity is a chronic inflammatory state in which adaptive and innate immunity mediators play key roles. Lymphopenia is an adaptive immunity marker and it has been related to poor outcomes and greater mortality. Objective: To determine the relationship between body mass index and lymphocyte count and its association with the survival of septic patients. Methods and materials: A cohort retrospective study of patients older than 18 years old with sepsis, septic shock and no history of autoimmune diseases nor immunosuppressor treatments. Outcomes included determining BMI and lymphopenia. Results: 206 patients were included, 8.7% with low weight, 46.6% with normal weight, 24.8% with normal weight, 19.9% with obesity. The group with the lowest BMI (median of 21.37) and lymphopenia was associated with the greatest mortality. The survival analysis revealed that a BMI lower than 22.5 and lymphopenia are independent risk factors for mortality. Conclusions: Obesity is associated to a higher lymphocyte count and a greater survival in sepsis and septic shock. Since BMI and lymphocyte count are statistically significant independent risk factors for mortality, we propose an APACHE II score adjusted to these variables.

Resumo: Introdução: Na sepse, a obesidade é um fator de proteção para mortalidade, denominando esse fenômeno de «paradoxo da obesidade¼. A obesidade é um estado inflamatório crônico, incluindo mediadores da imunidade inata e adaptativa. Um marcador de imunidade adaptativa é a linfopenia, que está relacionada a uma evolução desfavorável e maior mortalidade. Objetivo: Determinar a relação do índice de massa corporal (IMC) com a contagem de linfócitos e sua relação com a sobrevida em pacientes sépticos. Material e métodos: Estudo de coorte, retrospectivo em pacientes com sepse e / ou choque séptico com mais de 18 anos, sem doenças autoimunes ou tratamento imunossupressor, determinando o IMC e a linfopenia. Resultados: Foram incluídos 206 pacientes, sendo 8.7% com baixo peso, 46.6% com peso normal, 24.8% com sobrepeso, 19.9% com obesidade. O grupo com maior mortalidade com linfopenia apresentou os menores valores de IMC de 21.37 kg/m2. A análise de sobrevivência revelou que um IMC < 22.5 kg/m2 e a linfopenia são fatores de risco independentes para a mortalidade. Conclusão: A obesidade está relacionada à maior contagem de linfócitos e maior sobrevida em sepse e choque séptico. Como o IMC e a contagem de linfócitos são fatores independentes para mortalidade estatisticamente significante, propomos a escala APACHE II ajustada com essas variáveis.

Indicadores clínico epidemiológicos asociados a úlceras por presión en un hospital de Lima / Clinical epidemiological indicators associated with pressure ulcers in a hospital of Lima

Objetivo: Determinar los indicadores clínico-epidemiológicos asociados a úlceras por presión (UPP) en pacientes del servicio de Medicina del Hospital Nacional Hipólito Unanue durante los años 2016-2017. Métodos: Estudio observacional, analítico y retrospectivo, basándose en la revisión de historias clínicas. Se obtuvo una muestra no probabilística por conveniencia, calculándose el odds ratio (OR), aplicando intervalo de confianza al 95% y se utilizó la prueba del chi cuadrado, con un valor de p<0.05 como estadísticamente significativo. Resultados: Para la muestra se obtuvo 93 pacientes que cumplieron con los criterios del estudio; el 50,5% fueron varones, con una media de edad de 68 años (+21 años), siendo el 74.19% de la población total adultos mayores. Las localizaciones más frecuentes de UPP fueron a nivel sacro (77%) y talón (12.9%); asimismo, los estadios más frecuentes fueron: II (32.3%), IV (31.2%) y III (26.9%). La presencia de UPP grave estuvo asociada a: ser adulto mayor (OR: 3.12; IC95%: 1.2-8.2), hipoalbuminemia (OR: 6.23, IC95%: 1.8-21.1), anemia (OR: 4.31, IC95%: 1.2-14.9) y linfopenia (OR: 3.68; IC95%: 1.5-9). Conclusión: Los pacientes adultos mayores que presenten hipoalbuminemia, anemia o linfopenia tienen mayor riesgo para presentar úlceras por presión graves, las cuales interfieren de manera significativa en su calidad de vida.

Objective: To determine the clinical-epidemiological indicators associated with pressure ulcers (UPP) in patients of the Medicine Service of the Hipólito Unanue National Hospital during the years 2016-2017.Methods: Observational, analytical and retrospective study, based on the review of medical records. A non-probabilistic sample was obtained for convenience, calculating the odds ratio (OR), applying the 95% confidence interval and using the chi square test, with a value of p <0.05 as statistically significant. Results: For the sample, 93 patients were obtained who fulfilled the study criteria; 50.5% were male, with an average age of 68 years (+21 years), with 74.19% of the total population being older adults. The most frequent locations of UPP were at the sacral level (77%) and heel (12.9%); likewise, the most frequent stages were: II (32.3%), IV (31.2%) and III (26.9%). The presence of severe UPP was associated to: being older (OR: 3.12, 95% CI: 1.2-8.2), hypoalbuminemia (OR: 6.23, 95% CI: 1.8-21.1), anemia (OR: 4.31, 95% CI: 1.2- 14.9) and lymphopenia (OR: 3.68, 95% CI: 1.5-9). Conclusion: Elderly patients with hypoalbuminemia, anemia or lymphopenia are at greater risk of developing severe pressure ulcers, which significantly interfere with their quality of life.

[A first pilot study on the neonatal screening of primary immunodeficiencies in Spain: TRECS and KRECS identify severe T- and B-cell lymphopenia]. / Primer estudio piloto en España sobre el cribado neonatal de las inmunodeficiencias primarias: TRECS y KRECS identifican linfopenias T y B graves.

INTRODUCTION: Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) improves outcome of affected infants/children. The measurement of T-cell receptor excision circles (TRECS) and kappa-deleting recombination excision circles (KRECS) can identify neonates with severe T or B-cell lymphopenia. OBJECTIVES: To determine TRECS and KRECS levels from prospectively collected dried blood spot samples (DBS) and to correctly identify severe T and B-cell lymphopenia. MATERIAL AND METHODS: Determination of TRECS and KRECS by multiplex PCR from neonates born in two tertiary hospitals in Seville between February 2014 and May 2014. PCR cut-off levels: TRECS<15 copies/µl, KRECS<10 copies/µl, ACTB (ß-actin)>1000 copies/µl. Internal (XLA, ataxia telangiectasia) and external (SCID) controls were included. RESULTS: A total of 1068 out of 1088 neonates (mean GA 39 weeks (38-40) and BW 3238g (2930-3520) were enrolled in the study. Mean (median, min/max) copies/µl, were as follows: TRECS 145 (132, 8/503), KRECS 82 (71, 7/381), and ACTB 2838 (2763, 284/7710). Twenty samples (1.87%) were insufficient. Resampling was needed in one neonate (0.09%), subsequently giving a normal result. When using lower cut-offs (TRECS<8 and KRECS<4 copies/µl), all the samples tested were normal and the internal and external controls were correctly identified. CONCLUSION: This is the first prospective pilot study in Spain using TRECS/KRECS/ACTB-assay, describing the experience and applicability of this method to identify severe lymphopenias. The ideal cut-off remains to be established in our population. Quality of sampling, storage and preparation need to be further improved.