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.

Pattern of comorbidities and clinical profile of young adults who died due to severe coronavirus disease: A descriptive study

Introduction: Mortality due to coronavirus disease (COVID-19) is a significant problem among the non-elderly population. Aims: The primary objective was to estimate the prevalence of comorbidities among the deceased in the age group of 18–64 years and the secondary objective, was to describe their clinical profile. Settings and Design: The study setting was a tertiary care center catering to COVID-19 patients. This was a record-based descriptive study. Materials and Methods: Sampling strategy and Sample size: The formula used for sample size calculation is Z2 * P(1 – P) / d2. The sample size required was 97. The study period was from July 1 to November 30, 2021. Data collection: Demographic data including comorbidities, and clinical and laboratory features were studied. The laboratory investigations were done on the day of admission, and either on the last day or one day before death were taken for analysis. Statistical analysis used: Statistical analysis was carried out in IBM SPSS Version 26. Chi-square and Fisher’s exact tests, Mann–Whitney U and Kruskal–Wallis tests, Wilcoxon signed rank test, and Correlation tests were used for analysis. Results: The majority of the patients had more than one comorbid condition. The parameters which showed significant variation as the illness progressed were lymphocyte count, total protein, and albumin. Conclusion: Special vigilance should be kept while managing young patients with comorbidities. Lymphocyte count and serum albumin can be helpful in prognostication.

A Retrospective Study To Evaluate The Role Of Laboratory Biomarkers In Determining The Disease Severity And Early Detection Of Progression To Advanced Stage In Covid 19 Patients

Novel corona virus epidemic started in Dec 19 in Wuhan, China and soon it spread globally and became an international emergency Our objective was to study the role of hematological and biochemistry markers in assessing the disease severity and prognosis of laboratory confirmed, hospitalized Covid 19 patients. 130 patients were included in this cross- sectional retrospective study and divided into mild/moderate and severe/critical group. Correlation analysis was done for laboratory biomarkers.We found that mean age, lactate dehydrogenase (LDH), S. ferritin, urea, uric acid, D-dimer and S.creatinine of severely ill patients were significantly higher than those of patients with non-severe illness. Leucopenia and neutropenia were also associated with disease severity. Males were affected more than females with both mild and severe illness. Following parameters like S. Ferritin, LDH, TLC, neutrophil % can help in identifying the progression of disease from mild to severe and help in adopting appropriate measures in the management so that progression can possibly be prevented. Rising levels of some parameters like D.dimer, urea, uric acid and creatinine also help in explaining the prognosis of patient.

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.

Advances in prevention and treatment of radiation-induced lymphopenia / 中华放射肿瘤学杂志

Currently, radiotherapy has been found to induce lymphopenia in multiple solid tumors, which has been proven to be associated with poor prognosis. Radiation-induced lymphopenia (RIL) is associated with age, baseline lymphocyte count, tumor size and location and radiotherapy regimens (radiation fractionation, field size and technique), etc. In addition, several drugs and cytokines may help restore lymphocytes. Exploration of effective strategies to prevent or treat RIL may be an important future direction to improve prognosis of cancer patients.

Early changes within the lymphocyte population are associated with the long term prognosis in severely injured patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between early lymphocyte responses and the prognosis in severely injured patients.@*METHODS@#Consecutive patients with severe trauma who were treated in Peking University People's Hospital Trauma Medical Center between June 2017 and June 2020 were enrolled in this restropective chart-review study. According to the responses of lymphocyte after severe injury, the patients were divided into three groups, group 1: lymphopenia-returned to normal; group 2: persistent lymphopenia; group 3: never lymphopenic, and the outcome of 28 d were recorded. Clinical data such as gender, age, base excess, mechanism of injury, Glasgow coma scale (GCS), injury severity score (ISS) and massive blood transfusion were collected. Perform statistical analysis on the collected clinical data to understand the trend of lymphocyte changes in early trauma and the relationship with prognosis. In order to eliminate the interference of age, stratification was carried out according to whether the age was ≥ 65 years old, in different age groups, they were grouped according to whether the length of stay was ≥ 28 d, and the relationship between lymphocyte trend and length of stay was discussed.@*RESULTS@#A total of 83 patients were included, 66 males and 17 females. The main injury mechanisms were traffic accident injuries and high-altitude fall injuries. The average ISS was (30±11) points. 65 patients had lymphopenia on the day of injury, 32 of them returned to normal on the 5th day, and the rest did not recover; the other 18 patients had normal lymphocyte levels after injury. Patients which are failure to normalize lymphopenia within the first 5 days following admission was related with the long hospitalization time and higher 28 d mortality rate. After further stratification by age, failure to normalize lymphopenia within the first 5 days following admission in the elderly group (age ≥65 years) was a risk factor for prolonged hospital stay (≥28 d), P=0.04. While in younger group, a high level of neutrophils within the first 5 d following admission was a risk factor for bad outcome.@*CONCLUSION@#A failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality and longer hospital stay. This study reveals lymphocytes can be used as a reliable indicator for the prognostic evaluation.

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)

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.

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)

Research progress on the influencing factors and prognosis of radiation-induced lymphopenia / 中华放射肿瘤学杂志

Lymphocyte-led immunity plays an important role in the occurrence and development of tumors. It has been found that radiotherapy can induce lymphopenia in patients with solid tumors, and radiotherapy-induced lymphopenia (RIL) might be caused by the irradiation of circulating blood. The sensitivity to irradiation differs among different subtypes of lymphocytes. RIL can be affected by radiation fractionation, technique and volume. Meanwhile, it has been proven that RIL can significantly reduce the survival of patients with multiple solid tumors. In this article, relevant researches were reviewed, aiming to advance clinical treatment decisions and optimize radiotherapy protocols.

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.

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.

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.

Tratamiento exitoso de síndrome hemofagocítico secundario a infección por virus de Epstein Barr: Reporte de caso / Successful treatment of hemophagocytic syndrome secondary to Epstein-Barr virus infection: Report of a case

Se presenta el caso de un paciente varón de seis años de edad, con síndrome hemofagocítico secundario a infección por virus de Epstein-Barr. El paciente inició el cuadro con fiebre, hepatoesplenomegalia, falla hepática, trastornos de la coagulación, ferritina, triglicéridos y disminución de todas las líneas celulares hematológicas. El aspirado de médula ósea evidenció la presencia de citofagocitosis, por lo que inició tratamiento específico según protocolo HLH 2004, respondiendo favorablemente luego de cuatro semanas. Actualmente, el paciente continúa sus controles por la especialidad sin recaída de enfermedad, con adecuado desarrollo y crecimiento. En nuestro país, son escasos los reportes de síndrome hemofagocítico; sin embargo, puede resultar una patología más frecuente de la que estimamos por lo que, es importante reportar estos casos y más aún el éxito del tratamiento a fin de continuar mejorando su manejo y reporte.

We present the case of a six-year old male patient who presented with hemophagocytic syndrome secondary to Epstein Barr virus infection. The patient had fever, hepatosplenomegaly, liver failure, coagulation, ferritin, and triglyceride disorders, as well as a significant reduction of all blood cell populations. Bone marrow aspirate revealed the presence of autophagocytosis, so specific therapy according to the HLH 2004 protocol was started, and the patient satisfactorily responded after four weeks. Nowadays the patient still attends his control appointments, no relapse has been detected, and both his development and growth are adequate. Few reports on hemophagocytic syndrome have been published in Peru; however, this condition may be more frequent than previously thought. Therefore, it is important to report such cases, particularly successful experiences, aiming to improve management of this condition.

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.

Risk factors for secondary infection in the treatment with anti-neutrophil cytoplasmic antibody-associated vasculitis / 中华肾脏病杂志

Objective To investigate the clinical characteristics and risk factors of secondary infection in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods One hundred and eighteen patients newly diagnosed with AAV at the institute of nephrology,Tongji hospital affiliated to Huazhong university of science and technology,from 2012 to 2017,were analyzed retrospectively.Induction therapy included single corticosteroids,combination of corticosteroids with cyclophosphamide and combination of corticosteroids with other immunosuppressive agents.End point was defined as moderate to severe infection which was diagnosed by the clinical and radiological manifestation as well as microbiological evidences.The infection-related survival curve was drawn to reflect the time when the infection occurred.The clinical baseline variables in patients with and without infection were compared.Multivariate Logistic regression model was used to determine the independent predictors of infection.Receiver-operating characteristic curve (ROC) was plotted for evaluating the predictive value of lymphocyte on moderate to severe infection.Results During followup of median 3 months (1-30 months),88 infection episodes were found in 63 (53.4％) patients,of which 54 times (61.4％) occurred within 6 months after treatment,46 times (52.3％) happened within 3 months after treatment.The most common organ of infection was lung (62.5％),and the most common pathogen was bacteria (51.1％).Multivariate Logistic regression model showed that lung involvement (OR=4.44,95％ CI 1.59-12.41),moderate reduction of lymphocyte in follow-up (OR=5.69,95％ CI 2.05-15.85) and severe lymphocyte reduction (OR=36.28,95％CI 3.45-381.17) were independent risk factors of secondary infection in AAV patients (all P ＜ 0.05).ROC curve showed that the area under the curve of lymphocyte as a predictor of severe infection was 0.767 (95％ CI 0.64-0.89,P ＜ 0.05).Based on lymphocyte less than 0.49× 109/L which was the cut-off value for predicting severe infection,the sensitivity and the specificity were 83.9％ and 71.9％,respectively.Conclusions Lung involvement and moderate-severe lymphopenia during follow-up are independent risk factors of secondary infection in AAV patients.Hence,physician should pay more attention to those patients,and adjust treatment in time to avoid the occurrence of infection.

Correlation between treatment-related lymphopenia and pathologic response in esophageal squamous cell carcinoma patients undergoing neoadjuvant chemoradiotherapy / 中华放射肿瘤学杂志

Objective To investigate the relationship between treatment-related lymphopenia and pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).Methods Clinical data of 220 ESCC patients treated with neoadjuvant CRT followed by surgery between 2002 and 2016 were retrospectively analyzed.Absolute lymphocyte count was determined before and at 1 month after neoadjuvant CRT.Treatment-related lymphopenia was graded using Common Terminology Criteria for Adverse Events (CTCAE,4.0 version).The relationship between lymphopenia,pCR and recurrence was evaluated by chi-square test and Cox's regression model.Results Ninety-five patients (43.2％) achieved a pCR after neoadjuvant CRT and 71 cases (32.3％) recurred postoperatively.During neoadjuvant CRT,the incidence rates of grade 0,1,2,3,and 4 lymphopenia were 1.8％,6.8％,31.4％,38.2％,and 21.8％,respectively.Patients with grade 4 lymphopenia had a significantly lower pCR rate than those with grade 0-3 lymphopenia (22.9％ vs.48.8％,P=0.001).Moreover,grade 4 lymphopenia was significantly associated with a higher risk of recurrence (45.8％ vs.28.5％,P=0.023).Multivariate analysis identified that primary tumor length,tumor location and radiation dose were the independent predictors for grade 4 lymphopenia during neoadjuvant CRT (P=0.013,0.001,0.002).Conclusions The incidence of grade 4 lymphopenia in ESCC patients undergoing neoadjuvant CRT is correlated with a low pCR rate and a high risk of recurrence.Lymphopenia can be used as an economic and effective predictor for pCR.

Fatal Cryptococcus gattii meningitis with negative cryptococcal antigen test in a HIV-non-infected patient

Cryptococcus gattii predominantly causes central nervous system and pulmonary infection in both immunocompromised and immunocompetent patients with substantial morbidity. We report a case of rapidly fatal meningitis by C. gattii in an HIV–non-infected man with CD4 lymphopenia who tested negative for cryptococcal antigen. This case may serve as an alert to its wider occurrence and less explored risk factors.

An Infant with Respiratory Distress and Loose Stools

We present the case of a 3-month-old girl who was admitted with complaints of loose stools and respiratory distress. She also had ahistory of rash and alopecia. Laboratory investigations revealed lymphopenia with reduced immunoglobulin G and immunoglobulin A.Lymphocyte subset analysis by flow cytometry revealed T-B+NK+ severe combined immunodeficiency (SCID). She died due to severepneumonia, shock and pulmonary hemorrhage. Autopsy findings revealed disseminated cytomegalovirus infection in the lung, liver,adrenals and heart. Thymus was found to be dysplastic and showed characteristic histopathologic features of SCID.