Enrichment of effector memory T cells in the CD4 and CD8 T cell compartment during chronic graft versus host disease in children.

BACKGROUND: During allogeneic Hematopoietic stem cell transplantation (HSCT), frequent pathological scenarios include graft versus host disease (GVHD) and viral infections. We hypothesized if exogenous stimulus as alloantigen and viral antigens might impact on central and effector memory T cells in pediatric recipients. PATIENTS AND METHODS: Subjects included 21 pediatric recipients and 20 healthy children (control group). Peripheral blood samples of patients were collected along the first 712 days post-HSCT. T cell phenotyping of naïve, central, and effector memory T cells (TCMs and TEMs, respectively) was conducted using flow cytometry. Viral nucleic acids were detected using real-time PCR. RESULTS: T cell reconstitution was not reached after 1 year post-HSCT. Chronic GVHD was associated with increased numbers of naïve CD4 T cells (p < 0.05) as well as an increase in TEM and TCM cells of the CD4 (p < 0.0001 and p < 0.05, respectively) and CD8 T cell TEM (p < 0.0001). and TCM (p < 0.001) populations too. Moreover, BK and Epstein-Barr viruses were the main viral pathogens detected (<104 copies), which were associated with a decrease in all T cell compartments. CONCLUSION: During chronic GVHD, alloantigen persistence generates TEM cell enrichment among CD4 and CD8 T cells, and viral infections are associated with deficient recovery of T cells after HSCT.

Behavior of immunoglobulin G antibodies for SARS-COV-2 in Mexican pediatric patients with comorbidities: a prospective comparative cohort study.

Background: More than two years after the pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) there is a great lack of information. The presence of immunoglobulin G (IgG) have been related with disease severity. Patients with comorbidities could develop more severe infection; however, the evaluation of the humoral response in pediatric population are needed especially in patients with comorbidities. Our aim was to describe the behavior of IgG in pediatric patients and to know if there is a difference between patients with comorbidities. Methods: A prospective comparative cohort study was carried out in a single center from June 2020 to January 2021, with a follow-up of 6 months. The study included all the subjects with confirmatory test for SARS-CoV-2 from 1 month to 17 years 11 months, the follow-up of the disease's evolution and measurement of IgG antibodies was collected. We obtained the clinical data, and comorbidities like arterial hypertension, diabetes, obesity, and cancer, the initial symptoms were recorded as well as the evolution regarding the severity of COVID-19 and the need for hospitalization, intensive care unit or mechanical ventilation. The follow up was carried out through medical consultation with an appointment every month that included direct interrogation, examination, and peripheral blood collection for the IgG quantification. The antibodies detection was done through peripheral blood and chemiluminescence microparticle immunoassay. Results: A total of 237 patients with positive polymerase chain reaction (PCR) for SARS-COV-2 were included, of which 147 presented IgG antibodies (62%), 112 (76%) without comorbidity and 35 (24%) with comorbidities, by the sixth month only 2.7% continue with positive antibody measurements. Patients with comorbidities reach higher IgG levels than patients without comorbidities the basal titters were: 5.17 for patients without comorbidities vs. 6.96 for the group with comorbidities (P<0.001). Conclusions: We found an association between the presence of comorbidities and high levels of IgG units in pediatric patients with COVID-19. Additionally, patients with more severe course of the disease have higher levels of IgG and by the third month less than 35% have immunity.

Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype.

BACKGROUND: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). CASE REPORT: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. CONCLUSIONS: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.

INTRODUCCIÓN: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. CASO CLÍNICO: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. CONCLUSIONES: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.

Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype / Miosina 1g como un marcador de alto riesgo en una paciente pediátrica con cambio de linaje de leucemia linfoblástica aguda a fenotipo mieloide

Abstract Background: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). Case report: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. Conclusions: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.

Resumen Introducción: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. Caso clínico: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. Conclusiones: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.

Presence of antibodies against HLA class I and class II molecules in children before and after allo-HSCT. Alloantibodies before and after HSCT.

A severe complication of allogeneic hematopoietic stem cell transplantation (HSCT) is graft failure (GF). Among others, donor-specific anti-HLA antibodies (DSA) are associated with graft rejection after allogeneic or haploidentical transplantation in adults. Knowledge of DSA and pediatric recipients is limited. Hence, we aimed to generate more information about the presence of DSA (pre- and post-HSCT) and the clinical outcomes (graft rejection and poor function) in children. We identified DSA in 27% of the patients. We observed a higher frequency (50%) of DSA-bearing patients with a benign disease diagnosis than those diagnosed with leukemia (16.66%). We observed graft rejection in one patient (with DSA against two alleles of HLA class I molecules) and poor function in three recipients during the first 30 days after HSCT in the absence of DSA. The presence of donor and nondonor HLA-specific antibodies decreased substantially after transplantation. After the transplant, we identified two patients with DSA specific for HLA class I molecules (independent of clinical relevance), and four recipients showed PGF in the absence of DSA. We were unable to establish any association between the presence of DSA and a clinical outcome: graft failure or prevalence of viral infection.

Herpesvirus Screening in Childhood Hematopoietic Transplant Reveals High Systemic Inflammation in Episodes of Multiple Viral Detection and an EBV Association with Elevated IL-1ß, IL-8 and Graft-Versus-Host Disease.

Infections remain a major cause of morbidity and mortality among hematopoietic stem cell transplant (HSCT) recipients. Unlike Epstein-Barr Virus (EBV) and Human Cytomegalovirus (HCMV), Human Herpesvirus (HHV) 6, HHV7 and HHV8 are not routinely monitored in many centers, especially in the pediatric population of low-medium income countries. We screened EBV, HCMV, HHV6, HHV7 and HHV8 in 412 leukocytes-plasma paired samples from 40 pediatric patients assisted in a tertiary hospital in Mexico. Thirty-two underwent allo-HSCT, whereas eight received auto-HSCT. Overall viral detection frequencies in allo- and auto-HSCT were: EBV = 43.7% and 30.0%, HCMV = 5.0% and 6.7%, HHV6 = 7.9% and 20.0% and HHV7 = 9.7% and 23.3%. HHV8 was not detected in any sample. Interestingly, HHV6 and HHV7 were more frequent in auto-HSCT, and HHV6 was observed in all episodes of multiple detection in auto-HSCT patients. We found EBV DNA in plasma samples, whereas HCMV, HHV6 and HHV7 DNA were predominantly observed in leukocytes, indicative of their expansion in cellular compartments. We also found that IL-1ß, IL-2, IL-6 and IL-8 were significantly increased in episodes in which multiple viruses were simultaneously detected, and samples positive for EBV DNA and graft-versus-host disease had a further increase of IL-1ß and IL-8. In conclusion, the EBV, HCMV, HHV6 and HHV7 burdens were frequently detected in allo- and auto-HSCT, and their presence associated with systemic inflammation.

Clinical features and severe acute respiratory syndrome-coronavirus-2 structural protein-based serology of Mexican children and adolescents with coronavirus disease 2019.

Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection in children and adolescents primarily causes mild or asymptomatic coronavirus disease 2019 (COVID-19), and severe illness is mainly associated with comorbidities. However, the worldwide prevalence of COVID-19 in this population is only 1%-2%. In Mexico, the prevalence of COVID-19 in children has increased to 10%. As serology-based studies are scarce, we analyzed the clinical features and serological response (SARS-CoV-2 structural proteins) of children and adolescents who visited the Hospital Infantil de México Federico Gómez (October 2020-March 2021). The majority were 9-year-old children without comorbidities who were treated as outpatients and had mild-to-moderate illness. Children aged 6-10 years and adolescents aged 11-15 years had the maximum number of symptoms, including those with obesity. Nevertheless, children with comorbidities such as immunosuppression, leukemia, and obesity exhibited the lowest antibody response, whereas those aged 1-5 years with heart disease had the highest levels of antibodies. The SARS-CoV-2 spike receptor-binding domain-localized peptides and M and E proteins had the best antibody response. In conclusion, Mexican children and adolescents with COVID-19 represent a heterogeneous population, and comorbidities play an important role in the antibody response against SARS-CoV-2 infection.

Cell surface expression of GRP78 and CXCR4 is associated with childhood high-risk acute lymphoblastic leukemia at diagnostics.

Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GRP78 (sGRP78) is expressed on cancer cells but not in normal cells. Here, we explored the presence of sGRP78 in pediatric B-ALL at diagnosis and investigated the correlation with bona fide markers of leukemia. By using a combination of flow cytometry and high multidimensional analysis, we found a distinctive cluster containing high levels of sGRP78, CD10, CD19, and CXCR4 in bone marrow samples obtained from High-risk leukemia patients, which was absent in the compartment of Standard-risk leukemia. We confirmed that sGRP78+CXCR4+ blood-derived cells were more frequent in High-risk leukemia patients. Finally, we analyzed the dissemination capacity of sGRP78 leukemia cells in a model of xenotransplantation. sGRP78+ cells emigrated to the bone marrow and lymph nodes, maintaining the expression of CXCR4. Testing the presence of sGRP78 and CXCR4 together with conventional markers may help to achieve a better categorization of High and Standard-risk pediatric leukemia at diagnosis.

Screening for COVID-19 in Children Undergoing Elective Invasive Procedures.

OBJECTIVE: To report the frequency of asymptomatic infection with SARS-CoV-2 in pediatric patients undergoing invasive medical procedures in a tertiary pediatric hospital. METHODS: From June to October 2020, a SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) test was performed for all pediatric patients scheduled to undergo an elective invasive procedure. None of the patients was symptomatic. The cycle threshold (Ct) values of the ORF1ab gene were recorded for all patients. RESULTS: A total of 700 patients were screened for SARS-CoV-2 infection. The median age was 5.7 y old. In total, 46.6% (n = 326) of the patients were male, and 53.4% (n = 374) were female. The most common underlying diseases were hemato-oncological (25.3%), gastrointestinal (24.9%), and genitourinary (10.3%). The main scheduled surgical-medical procedures were surgical treatment for acquired congenital diseases, biopsy sampling, local therapy administration, organ transplantation, and the placement of central venous catheters, among others. The SARS-CoV-2 rRT-PCR test was positive in 9.4% (66), and the median Ct value was 35.8. None of the patients developed COVID-19. CONCLUSIONS: The frequency of asymptomatic SARS-CoV-2 infection was detected in less than 10% of pediatric patients scheduled to undergo an elective invasive procedure in a tertiary hospital. This frequency is higher than those in reports from different countries.

Respiratory viral infections in pediatric patients with hematopoietic stem cell transplantation.

Background: Viral respiratory infections in pediatric patients with hematopoietic stem cell transplantation (HSCT) significantly impact morbidity and mortality. It is necessary to determine the viral agents and their frequency of presentation to understand their impact on transplantation patients' evolution. Methods: From January 2017 to December 2019, we conducted a cross-sectional, descriptive, and observational study of patients who underwent HSCT with a viral respiratory infection. Viral identification was performed using multiplex polymerase chain reaction for nine respiratory viruses. Descriptive statistics were performed with a report of central tendency measures and percentages. Results: Of the 54 pediatric patients who underwent HSCT, 59.2% presented an airway infection; in turn, at least one viral agent was identified in 59.3% of these patients. The most frequent viral agents were influenza (25.9%), human rhinovirus (18.5%), and respiratory syncytial virus (18.5%). Viral co-infections occurred in 36.8% of the cases. The reported complications were supplemental oxygen requirement (73.6%), support with mechanical ventilation (21%), admission to the pediatric intensive care unit (15.7%), and mortality associated with a viral respiratory infection (10.5%). Conclusions: Viral respiratory infections are frequent in pediatric patients with HSCT; influenza A/B virus was the most frequent agent. As morbidity and mortality increase due to these infections in patients with HSCT, strategies are necessary for its prevention and timely treatment after transplantation.

Introducción: Las infecciones respiratorias virales en los pacientes pediátricos con trasplante de células progenitoras hematopoyéticas (TCPH) impactan significativamente la morbilidad y la mortalidad. Para comprender su impacto en la evolución de los pacientes receptores de trasplantes es necesario conocer la frecuencia de presentación y los agentes virales. Métodos: De enero de 2017 a diciembre de 2019 se llevó a cabo un estudio transversal, descriptivo y observacional de los pacientes sometidos a TCPH que tuvieron una infección viral de vías respiratorias. La identificación de los virus se realizó por medio de la prueba de reacción en cadena de la polimerasa multiplex para nueve virus respiratorios. Se realizó estadística descriptiva con reporte de medidas de tendencia central y porcentajes. Resultados: De los 54 pacientes incluidos, el 59.2% presentaron una infección de vías respiratorias y se identificó al menos un agente viral en el 59.3% de estos casos. Los virus más frecuentes fueron influenza (25.9%), rinovirus humano (18.5%) y virus sincitial respiratorio (18.5%). En el 36.8% de los casos se detectaron coinfecciones virales. Se presentaron las siguientes complicaciones: requerimiento de oxígeno suplementario (73.6%), soporte con ventilación mecánica (21%), ingreso a la unidad de cuidados intensivos pediátricos (15.7%) y muerte asociada a infección por virus respiratorios (10.5%). Conclusiones: Las infecciones respiratorias virales en los pacientes pediátricos con TCPH son frecuentes; el virus influenza A/B es el agente más habitual. Debido a que estas infecciones se asocian con mayor morbimortalidad en los pacientes con TCPH, son estrategias necesarias para su preven­ción y tratamiento oportuno posterior al trasplante.

Analytical recommendations for SARS-CoV-2 identification by RT-PCR in pediatric patients / Recomendaciones analíticas para la identificación de SARS-CoV-2 por RT-PCR en pacientes pediátricos

Abstract Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) and is currently listed as a global public health emergency. Timely identification and protocol implementations for molecular detection of this virus are vital for medical decision-making. Identification of SARS-CoV-2 infection cases is based on detection of the virus RNA by molecular tests, particularly real-time reverse transcription-polymerase chain reaction (RT-PCR). Technical and operational details specific to each center must be considered to perform the molecular diagnosis of SARS-CoV-2 in pediatric patients. The term “qualified laboratories” involves laboratories in which all users, analysts, and anyone reporting results are trained to develop and interpret results through a procedure implemented previously by an instructor. Such knowledge is essential in detecting and identifying errors during each of its phases: pre-analytical, analytical, and post-analytical, which allow the establishment of continuous improvement policies to ensure the quality of the results, but above all, the physical integrity of health workers.

Resumen La enfermedad por coronavirus de 2019 (COVID-19), causada por el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2), está catalogada actualmente como una emergencia de salud pública mundial. La oportuna identificación y la implementación de protocolos para la detección molecular de este virus son de vital importancia para la toma de decisiones médicas. La identificación de los casos de infección por SARS-CoV-2 se basa en la detección de ARN del virus mediante pruebas moleculares, específicamente la reacción en cadena de la polimerasa de transcripción inversa (RT-PCR) en tiempo real. Existen detalles particulares de cada centro, tanto técnicos como operacionales, que deben considerarse para llevar a cabo el diagnóstico molecular de SARS-CoV-2 en pacientes pediátricos. El término «laboratorios calificados¼ se refiere a laboratorios en los cuales todos los usuarios, los analistas y cualquier persona que reporta resultados están capacitados para el desarrollo y la interpretación de estos a través de un procedimiento previo implementado por un instructor. Dichos conocimientos son indispensables para la detección y la identificación de errores durante el proceso en cada una de sus fases: preanalítica, analítica y posanalítica. Además, permiten establecer políticas de mejora continua que aseguran la calidad de los resultados, pero sobre todo la integridad física de los trabajadores de la salud.

Respiratory viral infections in pediatric patients with hematopoietic stem cell transplantation / Infecciones respiratorias virales en pacientes pediátricos con trasplante de células progenitoras hematopoyéticas

Abstract Background: Viral respiratory infections in pediatric patients with hematopoietic stem cell transplantation (HSCT) significantly impact morbidity and mortality. It is necessary to determine the viral agents and their frequency of presentation to understand their impact on transplantation patients’ evolution. Methods: From January 2017 to December 2019, we conducted a cross-sectional, descriptive, and observational study of patients who underwent HSCT with a viral respiratory infection. Viral identification was performed using multiplex polymerase chain reaction for nine respiratory viruses. Descriptive statistics were performed with a report of central tendency measures and percentages. Results: Of the 54 pediatric patients who underwent HSCT, 59.2% presented an airway infection; in turn, at least one viral agent was identified in 59.3% of these patients. The most frequent viral agents were influenza (25.9%), human rhinovirus (18.5%), and respiratory syncytial virus (18.5%). Viral co-infections occurred in 36.8% of the cases. The reported complications were supplemental oxygen requirement (73.6%), support with mechanical ventilation (21%), admission to the pediatric intensive care unit (15.7%), and mortality associated with a viral respiratory infection (10.5%). Conclusions: Viral respiratory infections are frequent in pediatric patients with HSCT; influenza A/B virus was the most frequent agent. As morbidity and mortality increase due to these infections in patients with HSCT, strategies are necessary for its prevention and timely treatment after transplantation.

Resumen Introducción: Las infecciones respiratorias virales en los pacientes pediátricos con trasplante de células progenitoras hematopoyéticas (TCPH) impactan significativamente la morbilidad y la mortalidad. Para comprender su impacto en la evolución de los pacientes receptores de trasplantes es necesario conocer la frecuencia de presentación y los agentes virales. Métodos: De enero de 2017 a diciembre de 2019 se llevó a cabo un estudio transversal, descriptivo y observacional de los pacientes sometidos a TCPH que tuvieron una infección viral de vías respiratorias. La identificación de los virus se realizó por medio de la prueba de reacción en cadena de la polimerasa multiplex para nueve virus respiratorios. Se realizó estadística descriptiva con reporte de medidas de tendencia central y porcentajes. Resultados: De los 54 pacientes incluidos, el 59.2% presentaron una infección de vías respiratorias y se identificó al menos un agente viral en el 59.3% de estos casos. Los virus más frecuentes fueron influenza (25.9%), rinovirus humano (18.5%) y virus sincitial respiratorio (18.5%). En el 36.8% de los casos se detectaron coinfecciones virales. Se presentaron las siguientes complicaciones: requerimiento de oxígeno suplementario (73.6%), soporte con ventilación mecánica (21%), ingreso a la unidad de cuidados intensivos pediátricos (15.7%) y muerte asociada a infección por virus respiratorios (10.5%). Conclusiones: Las infecciones respiratorias virales en los pacientes pediátricos con TCPH son frecuentes; el virus influenza A/B es el agente más habitual. Debido a que estas infecciones se asocian con mayor morbimortalidad en los pacientes con TCPH, son estrategias necesarias para su prevención y tratamiento oportuno posterior al trasplante.

Hematopoietic stem cell transplantation in a patient with osteopetrosis and mutation in CLCN7: long-term follow-up / Trasplante de células progenitoras hematopoyéticas en un paciente con osteopetrosis y mutación en CLCN7: seguimiento a largo plazo

Abstract Background: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis. Case report: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. The patient underwent allogeneic HSCT (Allo-HSCT) using 100% compatible bone marrow from a related donor and received a myeloablative conditioning regimen and a CD34 cell dose (4.7 × 107/kg). In the early post-transplant, frequent complications such as pneumonitis, hypercalcemia, and hyperphosphatemia ocurred. With a suitable granulocytic graft and chimerism of 100%, it was considered a successful transplant. However, the patient showed a delayed platelet graft treated with a platelet-stimulating factor for 6 months. The patient is currently disease-free, outpatient follow-up, with no data on graft-versus-host disease, and no progressive neurological damage. Conclusions: Osteopetrosis is a childhood disease that requires clinical suspicion and early diagnosis. HSCT is necessary at an early age to prevent disease progression and sensorineural, hematological, and endocrinological functions damage that can lead to death.

Resumen Introducción: La osteopetrosis es una displasia ósea hereditaria poco común, caracterizada por una actividad osteoclástica deficiente que aumenta la densidad mineral ósea. Se considera que el trasplante de células progenitoras hematopoyéticas (TCPH) puede revertir las anormalidades esqueléticas y restaurar la hematopoyesis. Caso clínico: Se presenta el caso de un paciente de sexo masculino, de 3 años y 2 meses de edad, con diagnóstico tardío de osteopetrosis. Se realizó un TCPH alogénico de donador relacionado 100% compatible con médula ósea. Se utilizaron un régimen de acondicionamiento mieloablativo y una dosis celular de CD34 de 4.7 × 107/kg de peso. En el postrasplante temprano, el paciente desarrolló complicaciones como neumonitis, hipercalcemia e hiperfosfatemia. Con un injerto granulocítico adecuado y quimerismo del 100% se consideró un trasplante exitoso. Sin embargo, el paciente presentó retraso en el injerto plaquetario, por lo que se administró factor estimulante de plaquetas por 6 meses. Actualmente el paciente se encuentra libre de enfermedad, en seguimiento ambulatorio, sin datos de enfermedad del injerto contra el hospedero y con pruebas de neurodesarrollo sin deterioro neurológico progresivo. Conclusiones: La osteopetrosis es una enfermedad infantil que requiere una sospecha clínica y un diagnóstico temprano, ya que es necesario un TCPH a corta edad como tratamiento para evitar la progresión de la enfermedad y el deterioro de las funciones neurosensoriales, hematológicas y endocrinológicas que puede derivar en la defunción del paciente.

SARS-CoV-2 impact on oral health: a general view / Impacto del SARS-CoV-2 en la salud oral: una visión general

Abstract Coronavirus disease 2019 (COVID-19) is a new disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. China reported the first case of COVID-19 in December 2019, and a few months later, the World Health Organization declared it as a pandemic. Oral ulcers in adult patients have been associated with COVID-19. However, no cases have yet been documented in children. The angiotensin-converting enzyme-2 (ACE2) receptor has been identified in tissues of the oral cavity. Studies have identified the tongue as the site with the highest expression of ACE2, and the oral epithelium, gingival epithelium, and salivary glands as sites of lesser extent expression. ACE2 expression is lower in children and varies with age. SARS-CoV-2 in saliva has been identified in various studies, which suggests that this could be a useful sample for diagnosis. However, its presence in saliva would indicate the high risk of contagion of this fluid.

Resumen La COVID-19 es una nueva enfermedad causada por el SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo grave). El primer caso de COVID-19 se reportó en China en diciembre de 2019, y unos meses después la Organización Mundial de la Salud la declaró como una pandemia. En pacientes adultos se han asociado úlceras orales a la COVID-19; en niños aún no se han documentado casos. El receptor de la enzima convertidora de la angiotensina 2 (ECA2) se ha identificado en tejidos de la cavidad oral. Los estudios han identificado que la lengua es el sitio con mayor expresión del receptor de la ECA2, y el epitelio bucal, el epitelio gingival y las glándulas salivales lo son en menor medida. La expresión de la ECA2 es menor en los niños y va aumentando con la edad. En diversos estudios se ha identificado el SARS-CoV-2 en la saliva, lo que sugiere que podría ser una muestra útil para el diagnóstico de este virus. Sin embargo, su presencia en saliva indicaría un alto riesgo de contagio de este fluido.

Hematopoietic stem cell transplantation in a patient with osteopetrosis and mutation in CLCN7: long-term follow-up.

INTRODUCTION: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis. CLINICAL CASE: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. The patient underwent allogeneic HSCT (Allo-HSCT) using 100% compatible bone marrow from a related and received a myeloablative conditioning regimen and a CD34 cell dose (4.7 × 107/kg). In the early post-transplant, frequent complications such as pneumonitis, hypercalcemia, and hyperphosphatemia ocurred. With a suitable granulocytic graft and chimerism of 100%, it was considered a successful transplant. However, the patient showed a delayed platelet graft treated with a platelet-stimulating factor for 6 months. The patient is currently disease-free, outpatient follow-up, with no data on graft-versus-host disease, and no progressive neurological damage. CONCLUSION: Osteopetrosis is a childhood disease that requires clinical suspicion and early diagnosis. HSCT is necessary at an early age to prevent disease progression and sensorineural, hematological, and endocrinological functions damage that can lead to death.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient / Leucemia mieloide aguda asociada con t(16:21)(p11;q22) en un paciente pediátrico

Abstract Background: Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Resumen Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient.

Background: Background">Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

Clinical risk profile associated with SARS-CoV-2 infection and complications in the emergency area of a pediatric COVID-19 center / Perfil clínico de riesgo asociado a infección y complicaciones por SARS-CoV-2 en el área de urgencias de un centro pediátrico COVID-19

Abstract Background: In February 2020, the disease caused by the novel coronavirus (SARS-CoV-2), was classified as a pandemic. In the pediatric population, coronavirus disease (COVID)-19 has a reported mortality of less than 6% in complicated cases; however, the clinical characteristics and severity are not the same as those presented in the adult population. This study aimed to describe the clinical manifestations of patients younger than 18 years old and their association with the confirmation of the test and outcomes. Methods: We conducted an analytical cross-sectional study of symptoms suggestive for SARS-CoV-2 infection. All subjects with a confirmatory test for SARS-CoV-2 were included. Initial symptoms, history of influenza vaccination, and previous contact were documented, and mortality and the requirement for assisted mechanical ventilation were identified. The proportions of the variables were compared with the χ2 test. The odds ratio for a positive test and the requirement of intubation was calculated. Results: Of a total of 510 subjects, 76 (15%) were positive for SARS-CoV-2. The associated symptoms were chest pain, sudden onset of symptoms, and general malaise. The variable most associated with contagion was the exposure to a relative with a confirmed diagnosis of COVID-19. Infants and subjects without the influenza vaccine showed an increased risk for respiratory complications. Conclusions: The frequency of positivity in the test was 15% (infants and adolescents represented 64% of the confirmed cases), and the associated factors identified were contact with a confirmed case, sudden onset of symptoms, and chest pain.

Resumen Introducción: En 2019 se reportaron los primeros casos de SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo grave), causante de la COVID-19, que alcanzó el grado de pandemia en febrero de 2020. La presentación en la etapa pediátrica reporta una mortalidad menor del 6% en los casos complicados; sin embargo, las características clínicas y su gravedad no son iguales que en la población adulta. El objetivo de este estudio fue describir las manifestaciones clínicas de los pacientes menores de 18 años y su asociación con la confirmación de la prueba, la intubación endotraqueal y la muerte. Métodos: Estudio transversal analítico por cuadro sugestivo de infección por SARS-CoV-2. Se incluyeron sujetos positivos para SARS-CoV-2. Se documentaron los síntomas iniciales, los antecedentes de vacunación contra la influenza y los contactos previos, y se identificaron los desenlaces de mortalidad y requerimiento de ventilación mecánica asistida. Se compararon las proporciones de las variables con la prueba χ2 y se calculó la razón de momios para la presencia de una prueba positiva y requerir intubación. Resultados: De un total de 510 sujetos, 76 (15%) fueron positivos para SARS-CoV-2. Los síntomas asociados fueron dolor precordial, inicio súbito y malestar general. La variable asociada con mayor frecuencia el contagio fue la exposición a un familiar con COVID-19 confirmada. Los sujetos sin vacuna de la influenza presentaron un riesgo mayor de complicaciones respiratorias. Conclusiones: La frecuencia de positividad en la prueba fue del 15%. Se identificaron como factores asociados a prueba positiva el contacto con un caso confirmado de COVID-19, el inicio súbito de los síntomas y el dolor precordial.

Saliva as a promising biofluid for SARS-CoV-2 detection during the early stages of infection / La saliva como biofluido promisorio para la detección del SARS-CoV-2 durante las primeras etapas de la infección

Abstract Background: Diagnostic testing for coronavirus disease (COVID)-19 is performed using nasopharyngeal swabs. This type of sampling is uncomfortable for the patient, dangerous for health workers, and its high demand has led to a global shortage of swabs. One of the alternative specimens is saliva. However, the optimal conditions for the test have not been established. Methods: Reverse transcription-polymerase chain reaction was used to detect the viral genome in saliva samples kept at room temperature, in the fridge or frozen for 2 days. In addition, the influence of brushing teeth and feeding on the detection of the virus in saliva was addressed. Finally, the efficiency of saliva in revealing the presence of the virus during the hospitalization period was determined in children. Results: The viral genome was consistently detected regardless of the storage conditions of saliva samples. Brushing teeth and feeding did not influence the sensitivity of the test. In hospitalized children, positive results were obtained only during the early days. Conclusions: These results support the idea of the use of saliva as an alternative specimen for diagnostic testing for COVID-19. The viral genome is stable and endures perturbations in the oral cavity. However, clearance of the virus from the mouth during the infection may limit the use of the test only to the early stages of the disease.

Resumen Introducción: El diagnóstico de COVID-19 (enfermedad por coronavirus 2019) se realiza con un hisopado nasofaríngeo. El procedimiento de toma de muestra es molesto para el paciente y peligroso para el personal de salud, y la alta demanda de análisis ha conducido a la escasez de hisopos. Una alternativa es el uso de saliva, pero las condiciones óptimas para realizar el estudio no han sido establecidas. Métodos: Se usó la reacción en cadena de la polimerasa con transcriptasa reversa para detectar el genoma viral en muestras de saliva mantenidas a temperatura ambiente, en refrigeración o congeladas. Además, se evaluó la influencia del aseo bucal y de la ingesta de alimento en la detección del virus. Finalmente, se determinó el desempeño de la saliva para reportar la presencia del virus durante el periodo de hospitalización en niños. Resultados: El genoma viral fue estable durante 2 días a las diferentes temperaturas ensayadas. El aseo bucal y la ingesta de alimento no influyeron en la detección del virus. En los niños hospitalizados solo se obtuvieron resultados positivos durante los primeros días. Conclusiones: Los resultados coinciden con la idea del uso de la saliva como biofluido alternativo para el diagnóstico de COVID-19. El genoma viral es estable y no se ve afectado por perturbaciones en la cavidad oral; sin embargo, la dinámica de la infección puede provocar que el ensayo solo sea útil durante las primeras etapas de la enfermedad.

Natural killer cell reconstitution after hematopoietic stem-cell transplantation in children.

INTRODUCTION: After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cells reconstitution is the main barrier against viral infections. OBJECTIVE: To determine that the knowledge on the kinetics of NK cell reconstitution after HSCT contributes to transplant efficient monitoring, which increases the possibility of its success. METHOD: Twenty-one patients undergoing HSCT were included, as well as a control group of clinically healthy individuals. At different time points after transplantation (range of 21 to 670 days), CD3- CD16+ CD56+ NK cells were quantified by flow cytometry in peripheral blood samples. RESULTS: NK cell recovery occurs at three to six months and 10 to 12 months post-transplantation; their number was significantly lower (in comparison with the control group) in the rest of the monitoring time. CONCLUSIONS: The first period of NK cell recovery occurs between three and six months after transplantation. Reconstitution is transient and the number of NK cells varies in the first years.

INTRODUCCIÓN: Después de un trasplante de células progenitoras hematopoyéticas (TCPH), la reconstitución de las células natural killer (NK) es la principal barrera contra las infecciones virales. OBJETIVO: Determinar que el conocimiento sobre la cinética de la reconstitución de las células NK posterior al TCPH contribuye a un eficiente monitoreo del trasplante, lo que incrementa la posibilidad de éxito de este. MÉTODO: Se incluyeron 21 pacientes sometidos a TCPH, así como un grupo control de individuos clínicamente sanos. En diferentes momentos después del trasplante (intervalo de 21 a 670 días), mediante citometría de flujo se cuantificaron las células NK CD3− CD16+ CD56+ en muestras de sangre periférica. RESULTADOS: La recuperación de las células NK ocurre a los tres a seis meses y a los 10 a 12 meses postrasplante; su número fue significativamente menor (en comparación con el grupo control) en el tiempo restante del monitoreo. CONCLUSIONES: El primer periodo de recuperación de las células NK ocurre entre los tres y seis meses posteriores al trasplante. La reconstitución es transitoria y el número de células NK varía en los primeros años.