Características clínicas de pacientes hospitalizados con infección por Covid-19 en la Clínica SOMA de Medellín, Colombia / Clinical characteristics of hospitalized patients with Covid-19 infection at the SOMA Clinic in Medellín, Colombia / Características clínicas de pacientes hospitalizados com infecção por Covid-19 na Clínica SOMA em Medellín, Colômbia

Objetivo: el virus SARS-COV-2 llegó a Medellín el 9 de marzo del 2020, afectando hasta el 8 de octubre 2021 a 397.395 personas en esta ciudad. Este estudio busca describir el comportamiento clínico de los pacientes hospitalizados en la Clínica SOMA en el periodo entre julio 1 de 2020 y enero 31 de 2021, así como identificar variables clínicas y paraclínicas asociadas a su ingreso a UCI y la mortalidad. Metodología: cohorte retrospectiva con datos de historias clínicas de adultos admitidos en la Clínica SOMA por Covid-19 entre julio 1 de 2020 y enero 31 de 2021. Resultados: se identificaron 849 individuos adultos con Covid-19, de los cuales 326 fueron hospitalizados (38.4%), la mortalidad fue del 13%. Los factores más asociados a severidad fueron la disnea, hipertensión arterial, enfermedad cardiovascular, dímero D elevado, deshidrogenasa láctica, linfopenia y una mayor edad. Conclusiones: nuestro estudio evidenció un comportamiento similar al descrito en otros estudios en el mundo frente a variables al ingreso por Covid-19, que se asocian con peores desenlaces clínicos.

Objective: SARS COV-2 virus arrived in Medellin on March 9, 2020, affecting 397 395 people in Medellin by Oct 8, 2021. This study aims to describe the clinical behavior of patients hospitalized in SOMA Clinic between July 1st, 2020, and January 31st, 2021, and to identify clinical and paraclinical variables associated with ICU entry and mortality. Methodology: retrospective cohort with data from medical records of all patients over 18 years of age admitted to the SOMA Clinic for Covid-19 between July 1st, 2020, and January 31st, 2021. Results: 849 patients with Covid-19 consulted the emergency room of the SOMA Clinic, out of which 326 were hospitalized (38.4%) with a mortality of 13%. Dyspnea, hypertension, cardiovascular disease, elevated D-dimer values, lactic dehydrogenase, and lymphopenia and older age were associated with severity. Conclusions: like other studies worldwide, we evidenced clinical and paraclinical parameters at entry that are associated with worst clinical outcomes in a SARS-COV-2 infection.

Objetivo: o vírus SARS-COV-2 chegou a Medellín em 9 de março de 2020, afetando 397.395 pessoas nesta cidade até 8 de outubro de 2021. Este estudo busca descrever o comportamento clínico dos pacientes internados na Clínica SOMA no período entre 1º de julho de 2020 e 31 de janeiro de 2021, bem como identificar variáveis clínicas e paraclínicas associadas à sua admissão na UTI e mortalidade. Metodologia: coorte retrospectiva com dados de prontuários de adultos internados na Clínica SOMA por Covid-19 entre 1º de julho de 2020 e 31 de janeiro de 2021.Resultados: foram identificados 849 indivíduos adultos com Covid-19, dos quais 326 foram hospitalizados (38,4%), a mortalidade foi de 13%. Os fatores mais associados à gravidade foram dispneia, hipertensão arterial, doença cardiovascular, D-dímero elevado, desidrogenase lática, linfopenia e idade avançada. Conclusões: nosso estudo mostrou um comportamento semelhante ao descrito em outros estudos no mundo frente às variáveis na admissão por Covid-19, que estão associadas a piores desfechos clínicos.

The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Hematological changes in SARS-COV-2 positive patients

Abstract Introduction The novel SARS-CoV-2 infection has been spreading around the world since January 2020 causing the Corona Virus Disease 2019. Leukopenia, lymphopenia and hypercoagulability with elevated D- Dimers have been described in COVID-19 patients to date. This study aimed to clarify if some blood parameters can be used as biomarkers to facilitate diagnosis and establish prognosis. Methods: We selected patients who had tested positive for SARS-CoV-2 and had had a hemogram performed between the March 15 and April 15, 2020. Socio-demographic and analytical data were obtained from 274 patients at admission in two Portuguese public hospitals. We then analyzed the hemogram parameters at admission in the intensive care and collected data on patient survival during the SARS-CoV-2 disease follow-up. The data were analyzed using appropriate statistical tests. Results: Patients requiring the intensive care unit (ICU) present an increase in leukocytes and neutrophils (+3.1 × 109/L and +6.4 × 109/L, respectively), a lymphocyte decrease and a platelet rise (-1.6 × 109/L and +60.8 × 109/L, respectively). The erythrocytes, hemoglobin and median globular volume tend to decrease (-0.5 × 1012, - 1.2 g/dL; -3 fL, respectively). The lactic acid dehydrogenase (LDH) at admission was significantly higher (+58.1 U/L). The age, sex, platelets, lymphocyte count neutrophil counts, neutrophil/lymphocyte ratio, erythrocytes and cell hemoglobin concentration mean (CHCM) are independently associated with mortality (odds ratio (OR) = 0.046, p < 0.001; OR = 0.2364, p= 0.045; OR = 9.106, p= 0.001; OR = 0.194, p= 0.033; OR = 0.062, p= 0.003; OR = 0.098, p= 0.002; OR = 9.021, p < 0.001; OR = 7.016, p= 0.007, respectively). Conclusion The hematological data at admission in the health care system can predict the mortality of the SARS-CoV-2 infection and we recommend its use in the clinical decisions and patient prognosis evaluation.

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.

Moringa supplementation improves immunological indices and hematological abnormalities in seropositive patients receiving HAARTs

Background: Moringa oleifera Lam. is known to be of high nutritional and medicinal importance and has been demonstrated to possess a variety of biological activities. Objective: This study investigated the beneficial role of M. oleifera (moringa) supplementation in HIV positive subjects receiving antiretroviral drugs. Methods: Adult HIV positive individuals (104) attending the medical outpatient clinic in a tertiary health institution in Nigeria receiving highly active anti-retroviral therapies (HAARTs) were recruited in a randomized fashion for the study. Half of the subjects received moringa supplement (20 mg daily) additionally, while the others received only HAART and represented the control group. All subjects were monitored for 3 months during which their immunological status (CD4 counts and TNF-α), and hematological abnormalities at pre (baseline) and post study periods were determined. Results: Baseline levels of CD4 increased while TNF-α decreased significantly in control and moringa supplemented groups (p < 0.01). However, the post study CD4 values in the moringa group were higher and TNF-α values were lower compared to the control group (p < 0.01). In addition, baseline hematological abnormalities (anemia, thrombocytopenia, leucopenia, lymphopenia, and neutropenia) were improved but most significantly in the moringa supplemented subjects. Conclusion: The results suggest that moringa has immune-beneficial properties and improved hematological abnormalities in HIV positive individuals receiving antiretroviral therapy.

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)

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Criptococosis y linfocitopenia T CD4 idiopática: Reporte de un caso / Cryptococcosis and idiopathic CD4 T lymphocytopenia: A case report

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Clinical features of children with / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with @*METHODS@#A total of 310 MPP children who were hospitalized and underwent bronchoalveolar lavage from June 2018 to June 2019 were enrolled and divided into two groups: simple MPP group with 241 children (without peripheral lymphocytopenia) and MPP + peripheral lymphocytopenia group with 69 children. The two groups were compared in terms of clinical data and treatment outcome.@*RESULTS@#Compared with the simple MPP group, the MPP + peripheral lymphocytopenia group had significantly longer duration of fever and length of hospital stay and significant increases in C-reactive protein, lactate dehydrogenase, and @*CONCLUSIONS@#Children with MPP and peripheral lymphocytopenia tend to have more severe immunologic injury. Peripheral blood lymphocyte count may be used to evaluate the severity of MPP.

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.

Clinical characteristics of 34 COVID-19 patients admitted to intensive care unit in Hangzhou, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020.@*METHODS@#A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared.@*RESULTS@#The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization.@*CONCLUSIONS@#Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.

COVID-19: presentación clínica en adultos / COVID-19: clinical features in adult patients

Este artículo resume las diferentes formas de presentación clínica de la enfermedad COVID-19 causada por el virus SARS-Co-2 documentadas fundamentalmente en las tres principales revisiones sistemáticas disponibles. Entre las manifestaciones clínicas de frecuente aparición se destacan la fiebre (83 %), la tos (60 %) y la fatiga (38 %), seguidas por las mialgias (29 %), el aumento de la producción del esputo (27 %) y la disnea (25 %). Entre los hallazgos de laboratorio,predominan el aumento de los valores de proteína C reactiva (69 %), la linfopenia (57 %) y el aumento de los niveles de lactato-deshidrogenasa (52 %). Respecto de las manifestaciones radiológicas, tienen especial importancia las opacificaciones en vidrio esmerilado (80 %), la neumonía bilateral (73 %) y la afectación de tres lóbulos pulmonares o más (57 %).Si bien la evidencia sintetizada tiene limitaciones, permite una aproximación actualizada a los conocimientos disponibles sobre la clínica de esta nueva enfermedad en la población adulta. (AU)

This article summarizes the different forms of clinical presentation of COVID-19, caused by the SARS-Co-2 virus, synthesizing the information collected mainly by three published systematic reviews. Frequent clinical manifestations include fever(83 %), cough (60 %), and fatigue (38 %), followed by myalgia (29 %), increased sputum production (27 %) and dyspnea(25 %). Among the laboratory findings, the most common are the increase in C-reactive protein values (69 %), lymphopenia (57 %) and the increase in lactate dehydrogenase levels (52 %).. Most remarkable radiological features include ground glass opacifications (80 %), bilateral pneumonia (73 %) and the involvement of three or more lung lobes (57 %). Although the synthesized evidence has limitations, it allows an updated approach to the available knowledge about the clinical symptoms of this new disease in the adult population. (AU)

The autophagy Protein Atg5 Plays a Crucial Role in the Maintenance and Reconstitution Ability of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_Atg5(−/−) mice. The proliferation of Lin⁻Sca-1⁺c-Kit⁺ HSCs was aberrant in bone marrow of Vav_Atg5(−/−) mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.

Significance of Differential Characteristics in Infantile Kawasaki Disease

BACKGROUND AND OBJECTIVES: Immunological variability in Kawasaki disease (KD) shows age-specific differences; however, specific differences in laboratory values have not been compared between infants and non-infants with KD. We compared age-adjusted Z-values (Z) of white and red blood cells in infants with KD with those in non-infants with KD. METHODS: This study retrospectively investigated 192 infants and 667 non-infants recruited between 2003 and 2015 at the Korea University Hospital. Laboratory values for infants with KD and non-infants with KD were analyzed and age-unadjusted raw values (R) and age-adjusted Z for blood cells counts were determined. RESULTS: Z in infants with KD during pre-intravenous immunoglobulin (IVIG), post-IVIG, and chronic phases showed increased lymphopenia and eosinophilia, low neutrophil:lymphocyte and neutrophil:eosinophil ratios, worse anemia, increased thrombocytosis, and reduced erythrocyte sedimentation rates compared with those in non-infants with KD. The optimal cut-off value for pre-IVIG Z-hemoglobin for prediction of KD in all patients was 40 mg/L (AUC, 0.811; sensitivity/specificity, 0.712/0.700; p=0.04). CONCLUSIONS: Laboratory characteristics enable differentiation between infants and non-infants with KD and contribute to a better understanding of changes in blood cell counts. Infants with incomplete KD can be more easily differentiated from infants with simple febrile illness using pre-IVIG Z-hemoglobin and pre-IVIG CRP values.

The Effect of Mycophenolate Mofetil on Non-Renal Manifestations in Systemic Lupus Erythematosus: Results from Korean Lupus Network Registry

BACKGROUND: The objective of this study was to identify the effects of mycophenolate mofetil (MMF) on non-renal manifestations in systemic lupus erythematosus (SLE). METHODS: The study population comprised 439 SLE patients from the Korean Lupus Network registry who were followed up annually and completed the baseline survey and two follow-up visits from 2014 to 2018. Disease activity, laboratory markers, and clinical manifestations including mucocutaneous lesions, arthritis, serositis, neurological disorders, and hematologic/immunologic abnormalities were assessed. All variables by group (MMF and non-MMF) effects with time (baseline, 1st follow-up, and 2nd follow-up) were analyzed by generalized estimation equation. RESULTS: Seventy-two patients were treated with MMF. There was significant difference in frequencies of malar rash, arthritis, renal disorder, and hematologic disorder between MMF and non-MMF groups in total SLE patients. In subgroup analysis of hematologic abnormalities in total patients, frequency of leukopenia was significantly different between the two groups during follow-up (P = 0.001), but frequencies of hemolytic anemia, lymphopenia, and thrombocytopenia were not. In addition, frequencies of leukopenia in patients without lupus nephritis were significantly decreased in MMF group compared to non-MMF group (P = 0.012). CONCLUSION: This study showed that MMF might be a beneficial treatment for hematologic abnormalities, especially leukopenia, in SLE.

CRISPR/Cas9-mediated knockout of Rag-2 causes systemic lymphopenia with hypoplastic lymphoid organs in FVB mice / 한국실험동물학회지

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. RAG-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of RAG-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of RAG-2, we recently established a new RAG-2 knockout FVB mouse line (RAG-2(−/−)) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. RAG-2(−/−) mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in RAG-2(−/−) mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in RAG-2(−/−) mice. These findings indicate that our RAG-2(−/−) mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

Hematological findings and factors associated with feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) positivity in cats from southern Brazil / Achados hematológicos e fatores associados a positividade pelo vírus da leucemia felina (felv) e vírus da imunodeficiência felina em gatos do sul do Brasil

Using a retrospective study, 493 cats tested for FeLV and FIV were selected for analysis of the association between hematologic findings and positivity at immunoassay test. Individual and hematologic variables were assessed considering the influence of results using univariate and multivariate logistic regression analysis. Out 153 of the 493 cats were positive for FeLV (31%), 50 were positive for FIV (10.1%) and 22 were positive for both FIV and FeLV (4.4%). Multivariate analysis detected significant associations between FeLV infection and age below 1 year (p=0.01), age from 1 to 10 years (p=0.03), and crossbreed (p=0.04). Male cats were more likely to be FIV-positive (p=0.002). Regarding hematological changes, FeLV-positive cats have higher odds to anemia, leukopenia and lymphopenia than FeLV-negative cats. FIV-positive cats are more likely to have anemia than negative. Identification of associated factors related to animal status and correlation of hematological disorders with infection by retroviruses in cats could be useful for detecting these retroviral diseases in cats.(AU)

Através de um estudo retrospectivo, 493 gatos testados para FeLV e FIV foram selecionados para análise da associação entre as alterações hematológicas e a positividade no teste imunoenzimático. Variáveis individuais e hematológicas foram consideradas para verificar a influência dos resultados utilizando análise de regressão logística univariada e multivariada. Um total de 153 de 493 gatos avaliados foram positivos para o FeLV (31%), 50 foram positivos para o FIV (10,1%) e 22 foram positivos para FIV e FeLV (4,4%). Análise multivariada detectou uma associação significativa entre a infecção pelo FeLV e a idade abaixo de 1 ano (P=0,01), idade entre 1 a 10 anos (P=0,03) e raça mista (P=0,04). Gatos machos foram mais predispostos a serem positivos para FIV (P=0,002). Com base nas alterações hematológicas, gatos positivos para o FeLV tem maior odds para apresentar anemia, leucopenia e linfopenia que os negativos. Gatos positivos para FIV possuem maiores chances de apresentarem anemia que os gatos negativos. A identificação dos fatores associados à infecção relacionados ao perfil do animal e a correlação com os distúrbios hematológicos com a infecção, pode ser útil para detecção das doenças retrovirais em gatos.(AU)

Epidermodysplasia verruciformis associated with idiopathic CD4+ lymphopenia / Epidermodisplasia verruciforme asociada a linfopenia idiopática de CD4+

Abstract Epidermodysplasia verruciformis (EV) is an autosomal recessive disease of the skin commonly associated with EVER1 and EVER 2 mutations, and is characterized by high susceptibility to infections associated with certain types of human papillomavirus called EV-PVH. Patients have warty lesions on the skin of varying characteristics and are often associated with skin cancer, with a strong association being found with EVER1 and EVER2 mutation gene. The case presented below concerns an absolute CD4+ lymphopenia, and establishes the hypothesis of a possible mutation of the RHOH gene as its origin.

Resumen La epidermodisplasia verruciforme (EV) es una enfermedad de la piel autosómica recesiva, relacionada con la mutación EVER1 y EVER2, caracterizada por alta susceptibilidad a infecciones asociadas a ciertos tipos de papillomavirus humano llamadas EV-PVH. Los pacientes presentan lesiones verrucosas en la piel de características variadas y muchas veces asociadas a cáncer de piel no melanocítico, encontrándose una fuerte asociación con la mutación del gen EVER1 y EVER2. El caso que se presenta a continuación documenta linfopenia absoluta de CD4+ por lo que se plantea la hipótesis de una posible mutación del gen RHOH como etiología.

Doença sistêmica relacionada à IgG4 com linfopenia: relato de caso e breve revisão de literatura / IgG4-related systemic disease associated with lymphopenia: case report and brief literature review

A doença sistêmica relacionada à IgG4 é uma doença emergente, recentemente descrita, caracterizada clinicamente por aumento parcial ou total de um órgão, e, por isso, com amplo espectro de manifestações clínicas. Esta é uma doença sistêmica fibroinflamatória, patologicamente provocada pela infiltração de plasmoblastos IgG4 positivos que levam à inflamação eosinofílica do tecido e, consequentemente, fibrose estoriforme. Quando o diagnóstico é precoce, a melhora clínica e resposta sustentada com corticosteroides sistêmicos é impressionante. O diagnóstico é baseado em critérios patológicos, mas, recentemente, alguns trabalhos têm descrito que plasmoblastos no soro podem servir como um fator independente para auxiliar no diagnóstico da doença. Este artigo descreve uma apresentação atípica da doença relacionada à IgG4, em um paciente linfopênico com medição inconclusiva de plasmoblastos no soro.

IgG4-related systemic disease is a recently described, emerging condition, clinically characterized by partial or total enlargement of an organ, with a broad spectrum of clinical manifestations. It is a systemic fibroinflammatory condition caused by the infiltration of IgG4-positive plasmablasts that lead to eosinophilic inflammation of tissues and consequently storiform fibrosis. When diagnosis is early, clinical improvement and maintained response achieved with systemic corticosteroids is impressive. Diagnosis is based on pathological criteria, but recent papers have described that serum plasmablasts may serve as an independent factor to aid in diagnosis. This paper describes an atypical presentation of IgG4-related disease in a lymphopenic patient with inconclusive serum plasmablast measurement.

Lower Respiratory Tract Diseases Caused by Common Respiratory Viruses among Stem Cell Transplantation Recipients: A Single Center Experience in Korea

PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea. RESULTS: Seventy-one CRV-LRDs were identified in 67 (6.5%) patients. The human parainfluenza virus (HPIV) was the most common causative pathogen of CRV-LRDs at 100 days [cumulative incidence estimate, 23.5%; 95% confidence interval (CI), 3.3–43.7] and 1 year (cumulative incidence estimate, 69.2%; 95% CI, 45.9–92.5) following SCT. The 30-day overall mortality rates due to influenza-LRDs, respiratory syncytial virus-LRDs, HPIV-LRDs, and human rhinovirus-LRDs were 35.7, 25.8, 31.6, and 42.8%, respectively. Co-pathogens in respiratory specimens were detected in 23 (33.8%) patients. The overall mortality at day 30 after CRV-LRD diagnosis was 32.8% (22/67). High-dose steroid usage (p=0.025), a severe state of immunodeficiency (p=0.033), and lymphopenia (p=0.006) were significantly associated with death within 30 days following CRV-LRD diagnosis in a univariate analysis. Multivariate logistic regression analysis revealed that high-dose steroid usage [odds ratio (OR), 4.05; 95% CI, 1.12–14.61; p=0.033] and lymphopenia (OR, 6.57; 95% CI, 1.80–24.03; p=0.004) were independent risk factors for mortality within 30 days of CRV-LRDs. CONCLUSION: CRV-LRDs among SCT recipients showed substantially high morbidity and mortality rates. Therefore, the implement of an active diagnostic approaches for CRV infections is required for SCT recipients with respiratory symptoms, especially those receiving high-dose steroids or with lymphopenia.