[Budd Chiari syndrome secondary to antiphospholipid syndrome and systemic lupus erythematosus in an adolescent: a case report]. / Síndrome de Budd Chiari secundario al síndrome antifosfolipídico y lupus eritematoso sistémico en una adolescente: reporte de un caso.

Budd-Chiari syndrome is caused by an obstruction of blood flow to the liver. Published cases of the antiphospholipid syndrome associated with BCS are limited in the pediatric population. We report a 15-year-old adolescent who presented with fever, ascites, and hepatosplenomegaly. Hepatic Doppler ultrasound revealed no flow in the right and middle hepatic veins and in the inferior vena cava. Abdominal tomography revealed extensive thrombosis of the inferior vena cava. During hospitalization, she was diagnosed with antiphospholipid syndrome and systemic lupus erythematosus. She was given treatment with unfractionated heparin, low molecular weight heparin, and anticoagulants. Budd-Chiari syndrome secondary to the antiphospholipid syndrome is a life-threatening disease. Timely diagnosis and treatment improve the quality of life of the patient.

A Multicenter Study on the Clinical Characteristics and Outcomes Among Children With Moderate to Severe Abusive Head Trauma.

INTRODUCTION: We aimed to identify clinical characteristics, risk factors for diagnosis, and describe outcomes among children with AHT. METHODS: We performed an observational cohort study in tertiary care hospitals from 14 countries across Asia and Ibero-America. We included patients <5 years old who were admitted to participating pediatric intensive care units (PICUs) with moderate to severe traumatic brain injury (TBI). We performed descriptive analysis and multivariable logistic regression for risk factors of AHT. RESULTS: 47 (12%) out of 392 patients were diagnosed with AHT. Compared to those with accidental injuries, children with AHT were more frequently < 2 years old (42, 89.4% vs 133, 38.6%, p < 0.001), more likely to arrive by private transportation (25, 53.2%, vs 88, 25.7%, p < 0.001), but less likely to have multiple injuries (14, 29.8% vs 158, 45.8%, p = 0.038). The AHT group was more likely to suffer subdural hemorrhage (SDH) (39, 83.0% vs 89, 25.8%, p < 0.001), require antiepileptic medications (41, 87.2% vs 209, 60.6%, p < 0.001), and neurosurgical interventions (27, 57.40% vs 143, 41.40%, p = 0.038). Mortality, PICU length of stay, and functional outcomes at 3 months were similar in both groups. In the multivariable logistic regression, age <2 years old (aOR 8.44, 95%CI 3.07-23.2), presence of seizures (aOR 3.43, 95%CI 1.60-7.36), and presence of SDH (aOR 9.58, 95%CI 4.10-22.39) were independently associated with AHT. CONCLUSIONS: AHT diagnosis represented 12% of our TBI cohort. Overall, children with AHT required more neurosurgical interventions and the use of anti-epileptic medications. Children younger than 2 years and with SDH were independently associated with a diagnosis of AHT. TYPE OF STUDY: Observational cohort study. LEVEL OF EVIDENCE: III.

Can the ROX index predict high-flow nasal cannula failure in children under 2 with lower respiratory tract infection?

OBJECTIVE: This study evaluates the ROX index's accuracy in predicting the success or failure of high-flow nasal cannula (HFNC) therapy in children under 2 years with acute respiratory failure (ARF) from lower respiratory tract infections. METHODS: From January 2018 to 2021 we conducted this multicenter retrospective cohort study, which included patients aged 2-24 months. We aimed to assess HFNC therapy outcomes as either success or failure. The analysis covered patient demographics, diagnoses, vital signs, and ROX index values at intervals from 0 to 48 h after initiating HFNC. We used bivariate analysis, repeated measures ANOVA, multivariate logistic regression, and the area under the receiver operating characteristic (AUC-ROC) curve for statistical analysis. RESULTS: The study involved 529 patients from six centers, with 198 females (37%) and a median age of 9 months (IQR: 3-15 months). HFNC therapy failed in 38% of cases. We observed significant variability in failure rates across different centers and physicians (p < .001). The ROX index was significantly associated with HFNC outcomes at all time points, showing an increasing trend in success cases over time (p < .001), but not in HFNC failure cases. Its predictive ability is limited, with AUC-ROC values ranging from 0.56 at the start to 0.67 at 48 h. CONCLUSION: While the ROX index is associated with HFNC outcomes in children under 2 years, its predictive ability is modest, impacted by significant variability among patients, physicians, and centers. These findings emphasize the need for more reliable predictive tools for HFNC therapy in this patient population.

Severe Pediatric Neurological Manifestations With SARS-CoV-2 or MIS-C Hospitalization and New Morbidity.

Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Hyperferritinemic sepsis secondary to invasive Toxoplasma gondii in a child with untreated HIV.

Background: Untreated human immunodeficiency virus (HIV)-immunosuppressed pediatric patients show high morbidity and mortality from opportunistic infections. Limited cases of hyperferritinemic sepsis have been described in patients with toxoplasmosis. Case report: We describe the case of a 13-year-old female patient with a history of untreated HIV who presented with hyperferritinemic sepsis secondary to Toxoplasma gondii infection and Pneumocystis jirovecci pneumonia. She received ventilatory support, inotropic drugs, treatment for opportunistic germs, and high-dose corticosteroids, but with unfavorable evolution. Conclusions: The global approach to sepsis with elevated ferritin guides to using of therapies aimed at neutralizing the severe inflammatory response. A timely diagnosis would allow prompt treatment and minimize complications.

Introducción: Los pacientes pediátricos inmunodeprimidos por el virus de la inmunodeficiencia humana (VIH) sin tratamiento presentan una elevada morbilidad y mortalidad por infecciones oportunistas. Se han descrito limitados casos de sepsis hiperferritinémica en pacientes con toxoplasmosis. Caso clínico: Se describe el caso de una paciente de 13 años con antecedente de VIH sin tratamiento que presentó sepsis hiperferritinémica secundaria a una infección por Toxoplasma gondii y neumonía por Pneumocystis jirovecci. Recibió soporte ventilatorio, uso de inotrópicos, tratamiento para gérmenes oportunistas y corticoides en altas dosis, pero su evolución fue desfavorable. Conclusiones: El abordaje global de la sepsis con ferritina elevada orienta a utilizar terapias dirigidas a neutralizar la respuesta inflamatoria severa, por lo que un diagnóstico oportuno permitiría iniciar el tratamiento prontamente y minimizar las complicaciones.

A brief history of crystalloids: the origin of the controversy.

Fluid resuscitation with crystalloids has been used in humans for more than 100 years. In patients with trauma, sepsis or shock of any etiology, they can help modify the clinical course of the illness. However, these solutions are medications which are not side-effect free. Recently, they have been questioned in terms of quantity (fluid overload) and their composition. The most frequently used crystalloids, both in high and low-income countries, are 0.9% normal saline (NS) and Ringer's lactate. The first descriptions of the use of sodium and water solutions in humans date from the cholera epidemic which spread throughout Europe in 1831. The composition of the fluids used by medical pioneers at that time differs greatly from the 0.9% NS used routinely today. The term "physiological solution" referred to fluids which did not cause red blood cell hemolysis in amphibians in in vitro studies years later. 0.9% NS has an acid pH, a more than 40% higher chloride concentration than plasma and a strong ion difference of zero, leading many researchers to consider it an unbalanced solution. In many observational studies and clinical trials, this 0.9% NS composition has been associated with multiple microcirculation and immune response complications, acute kidney injury, and worse clinical outcomes. Ringer's lactate has less sodium than plasma, as well as other electrolytes which can cause problems in patients with traumatic brain injury. This review provides a brief summary of the most important historical aspects of the origin of the most frequently used intravenous crystalloids today.

Short-, mid-, and long-term complications after multisystem inflammatory syndrome in children over a 24-month follow-up period in a hospital in Lima-Peru, 2020-2022.

Objective: To determine the short-, mid-, and long-term complications after multisystem inflammatory syndrome in children (MIS-C) over a 24-month follow-up period in a hospital in Lima, Peru, 2020-2022, and to explore differences according to the immunomodulatory treatment received and type of SARS-CoV-2 virus circulating. Methods: Ambispective 24-month follow-up study in children <14 years of age diagnosed with MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (HNERM). Results: A total of 62 children were admitted with MIS-C. The most common short-term complications and serious events were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) due to respiratory failure, and shock; predominantly during the second pandemic wave (lambda predominance) and in children that received intravenous immunoglobulin (IVIG) plus a corticosteroid. Two patients died during the first wave due to MIS-C. During prospective follow-up (median of 24 months; IQR: 16.7-24), only 46.7% of patients were followed for >18-24 months. Of the total, seven (11.3%) patients were identified with some sequelae on discharge. Among the 43 remaining children, sequelae persisted in five (11.6%) cases (neurological, hematological, and skin problems). Six patients (13.9%) presented with new onset disease (hematologic, respiratory, neurological, and psychiatric disorders). One patient died due to acute leukemia during the follow-up period. None of them were admitted to the ICU or presented with MIS-C reactivation. Two patients presented persistence of coronary aneurysm until 8- and 24-month post-discharge. Conclusion: In our hospital, children with MIS-C frequently developed short-term complications and serious events during the acute phase, with less frequent complications in the mid- and long-term. More studies are required to confirm these findings.

Lung mechanics in pediatric acute respiratory distress syndrome associated to acute COVID-19 and MIS-C: implications for therapies and outcomes. / Mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico asociado a COVID-19 aguda y MIS-C.

OBJECTIVE: To describe lung mechanics in Pediatric Acute Respiratory Distress Syndrome (PARDS) associated with acute COVID-19 and MIS-C with respiratory failure. METHODS: A concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICU) in Peru. The subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operating characteristic (ROC) curve analysis for mortality and lung mechanics was performed. RESULTS: 30 patients were included. The age was 7.5 (4-11) years, 60% were male, and mortality was 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS groups. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p < 0.001). C-PARDS group had more profound hypoxemia (P/F ratio < 100, 86% vs. 38%, p < 0.01) and higher driving-pressure [14(10-22) vs 10(10-12) cmH2O], and lower compliance of the respiratory system (CRS) [0.5 (0.3-0.6) vs 0.7(0.6-0.8) ml/ kg/cmH2O] compared with MIS-PARDS (all p < 0.05). The ROC analysis for mortality showed that driving pressure had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-off point of 15 cmH2O (100% sensitivity and 87% specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS (p = 0.09). MV-free days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS (p = 0.02). CONCLUSION: Patients with C-PARDS have lung mechanics characteristics similar to classic moderate to severe PARDS. This was not observed in patients with MIS-C. As seen in other studies, a driving pressure ≥ 15 cmH2O was the best discriminator for mortality. These findings may help guide ventilatory management strategies for these two different presentations.

Characteristics of pediatric patients hospitalized with COVID-19 during the third wave (omicron variant) at a referral hospital in Peru. / Características de los pacientes pediátricos hospitalizados con COVID-19 durante la tercera ola (variante ómicron) en un hospital de referencia del Perú.

OBJECTIVES.: Motivation for the study. There are few reports on the clinical experience of the population infected with the omicron variant of COVID-19 in Latin America, particularly in pediatric population. Main findings. There was a rapid increase in the number of hospitalizations compared to previous waves, mainly due to respiratory conditions; most patients progressed favorably. Antibiotics and corticosteroids were the most used drugs. Implications. Studying the characteristics of children hospitalized during the third wave of COVID-19 in Peru may increase the knowledge of how the omicron variant affects this population group, which will allow comparisons with possible new waves or diseases.

Difficult acute lymphoblastic leukaemia diagnosis in a paediatric patient with mixed presentation of COVID-19 acute respiratory failure and multisystemic inflammatory syndrome.

New diagnoses of leukaemia and other malignancies are recently being made in paediatric patients with COVID-19. The rates of mortality and morbidity in some of these children are expected to be higher. In new cases, concurrent diagnosis can be difficult because multisystemic inflammatory syndrome (MIS-C) and malignancies have similar clinical presentations. We present the case of a preteenage child where the diagnosis of leukaemia was complicated and delayed by a multisystem involvement and an inconclusive bone marrow study. Clinical teams managing children with COVID-19 and MIS-C should suspect leukaemia and other malignancies when the clinical course is complicated and bone marrow suppression is persistent. Prompt diagnosis will allow start of treatment on time, minimising complications.

Methylene blue for the treatment of refractory septic shock secondary to listeriosis in a paediatric patient.

Current therapies frequently used for refractory septic shock include hydrocortisone, vasopressin, extracorporeal membrane oxygenation (ECMO) support, inodilators, levosimendan and methylene blue. The evidence for these treatments is very limited. We present a case of a 5-year-old patient with refractory septic shock, secondary to Listeria monocytogenes meningitis. She presented with status epilepticus and developed septic shock. Shock persisted despite multiple high-dose vasoactive medications. ECMO support was not available. The medical team decided to use methylene blue to revert the vasoplegia, with excellent results. Shortly after the administration, vasopressors were weaned off and the high lactate cleared. She developed severe neurological sequelae due to brain haemorrhage secondary to the Listeria meningitis. The evidence supporting methylene blue for refractory septic shock in paediatric patients is limited. This case represents the effectiveness of this therapy without secondary effects.

Thrombotic thrombocytopenic purpura associated with COVID-19 in a critically ill child: a Peruvian case report.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare disease. In middle and low-income countries, specific resources are required for its diagnosis due to the lack of diagnostic tests and the variable response to plasma exchange, especially in the context of the new SARS-CoV-2 pandemic. CASE REPORT: We report the case of a 9-year-old male Hispanic patient with SARS-CoV-2 infection, atypical presentation, and multisystem involvement, thrombotic microangiopathy with dermal manifestations, hematologic, renal, and neurologic involvement. The patient was followed up after SARS-CoV-2 infection, the PLASMIC score was applied, and a genetic study was performed. Ventilation and hemodynamic support, corticotherapy, immunoglobulins, plasma exchange, renal replacement therapy, and monoclonal antibodies were given without favorable response. CONCLUSIONS: TTP associated with SARS-CoV-2 in the pediatric population is rare. However, resources for the diagnosis, support, and management of patients with TTP are required to avoid fatal outcomes.

INTRODUCCIÓN: La púrpura trombocitopénica trombótica (PTT) adquirida es una enfermedad poco frecuente. En los países de mediano y bajo estatus económico se requieren recursos para el diagnóstico de la PTT, debido a la falta de pruebas diagnósticas y a la respuesta variable al recambio plasmático, especialmente en el contexto de la pandemia por el nuevo SARS-CoV-2. CASO CLÍNICO: Paciente de sexo masculino, de 9 años, hispano, con infección por SARS-CoV-2, presentación atípica y afectación multisistémica, microangiopatía trombótica con manifestaciones dérmicas, y compromiso hematológico, renal y neurológico. Se dio seguimiento posinfección por SARS-CoV-2, se aplicó la escala PLASMIC y se realizó un estudio genético. Se aplicaron soporte ventilatorio y hemodinámico, corticoterapia, inmunoglobulinas, recambio plasmático, terapia de reemplazo renal y anticuerpos monoclonales, sin respuesta favorable. CONCLUSIONES: La PTT asociada al SARS-CoV-2 en la población pediátrica es poco frecuente. Aun así, se requieren recursos para el diagnóstico, el soporte y el manejo de los pacientes con PTT para evitar desenlaces fatales.

Posterior reversible encephalopathy syndrome in a child with severe multisystem inflammatory syndrome due to COVID-19. / Síndrome da encefalopatia posterior reversível em uma criança com síndrome inflamatória multissistêmica grave devido à COVID-19.

Posterior reversible encephalopathy syndrome is a rare clinical and radiological syndrome characterized by vasogenic edema of the white matter of the occipital and parietal lobes, which are usually symmetrical, resulting from a secondary manifestation of acute dysfunction of the posterior cerebrovascular system. We describe a case of posterior reversible encephalopathy syndrome secondary to SARS-CoV-2 infection in a 9-year-old boy who developed acute hypoxemic respiratory failure and required assisted mechanical ventilation. The child developed multisystem inflammatory syndrome, and he was monitored in the pediatric intensive care unit and was provided mechanical ventilation and vasoactive agents for hemodynamic support. Additionally, he developed pulmonary and extrapulmonary clinical manifestations along with neuropsychiatric manifestations that required close follow-up and were verified using brain magnetic resonance imaging for timely intervention. Currently, there are few reports of children with posterior reversible encephalopathy syndrome associated with multisystem inflammatory syndrome.

A síndrome da encefalopatia posterior reversível é uma rara síndrome clínica e radiológica caracterizada por edema vasogênico da matéria branca dos lobos occipital e parietal, que geralmente são simétricos, resultante de uma manifestação secundária de disfunção aguda do sistema cerebrovascular posterior. Descrevemos um caso de síndrome de encefalopatia posterior reversível secundária à infecção por SARS-CoV-2 em um menino de 9 anos de idade que desenvolveu insuficiência respiratória hipoxêmica aguda e necessitou de ventilação mecânica assistida. A criança desenvolveu síndrome inflamatória multissistêmica e foi monitorada na unidade de terapia intensiva pediátrica, tendo-lhe sido fornecidos ventilação mecânica e agentes vasoativos para suporte hemodinâmico. Além disso, desenvolveu manifestações clínicas pulmonares e extrapulmonares juntamente de manifestações neuropsiquiátricas que necessitavam de seguimento cuidadoso, tendo sido verificadas por ressonância magnética cerebral para intervenção oportuna. Atualmente, há poucos relatos de crianças com síndrome da encefalopatia posterior reversível associada à síndrome inflamatória multissistêmica.

Paediatric critical COVID-19 and mortality in a multinational prospective cohort.

Background: To understand critical paediatric coronavirus disease 2019 (COVID-19) and evaluate factors associated with mortality in children from high and low-middle income countries. Methods: Prospective, observational study of critically ill children hospitalised for COVID-19 in 18 countries throughout North America, Latin America, and Europe between April 1 and December 31, 2020. Associations with mortality were evaluated using logistic regression. Findings: 557 patients (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Invasive (41%) or non-invasive (20%) ventilation and vasopressors (56%) were the most common support modalities. Hospital mortality was 10% and higher in children <2 years old (15%; odds ratio 1·94, 95%CI 1·08-3·49). Most who died had pulmonary disease. When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2·89; 95%CI 1·2-6·94) or pulmonary comorbidities (aOR 4·43; 95%CI 1·70-11·5), admission hypoxemia (aOR 2·44; 95%CI 1·30-4·57), and lower respiratory symptoms (aOR 2·96; 95%CI 1·57-5·59). MIS-C (aOR 0·25; 95%CI 0·1-0·61) and receiving methylprednisolone (aOR 0·5; 95%CI 0·25-0·99), IVIG (aOR 0·32; 95%CI 0·16-0·62), or anticoagulation (aOR 0·49; 95%CI 0·25-0·95) were associated with lower mortality although these associations might be limited to children >2 years old. Interpretation: We identified factors associated with COVID-19 mortality in critically ill children from both high and low-middle income countries, including higher mortality with younger age and COVID-related pulmonary disease but lower mortality in MIS-C. Further research is needed on optimal treatments for younger children and respiratory failure in paediatric COVID-19. Funding: None.

[Clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19]. / Fenotipos clínicos del síndrome inflamatorio multisistémico pediátrico asociado a COVID-19 (SIM-C).

The multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is infre quent but potentially lethal. There are few reports of this disease and its phenotypes in Latin America. OBJECTIVE: To describe the characteristics of the clinical phenotypes of MIS-C in hospitalized patients in Lima, Peru. PATIENTS AND METHOD: A descriptive and retrospective study in patients under 14 years old with a diagnosis of MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (Lima, Perú), from April 2020 to August 2021. Clinical-demographic and microbiological variables were recorded. According to these, patients with MIS-C were classified into the shock phenotype, Kawasaki disease (KD) without shock, and the fever and inflammation phenotype, analyzing their clinical outcomes. RESULTS: 58 patients were analyzed. 32 (55.2%) presented the shock phenotype, 15 (25.8%) Kawasaki disease (KD) phenotype without shock, and 11 (19%) fever and inflammation phenotype. In the shock phenotype, 17 had KD. The mean age was 7 ± 3.5 years and 67.2% were males. Gastrointes tinal and mucocutaneous manifestations predominated in all phenotypes. The mortality was 3.5%. The frequency of coronary aneurysms was 10.2%. Most patients received immunomodulatory and antiplatelet treatment. Patients with shock phenotype showed greater involvement in inflammatory markers, hematological dysfunction, and myocardial injury, with a higher frequency of respiratory failure and invasive mechanical ventilation. CONCLUSIONS: In our case series, patients with shock phenotype were the most frequent and had worse clinical outcomes. Active surveillance of clinical phenotypes is needed to make an early diagnosis and management to improve the prognosis in these patients.

Association of Cancer Diagnosis and Therapeutic Stage With Mortality in Pediatric Patients With COVID-19, Prospective Multicenter Cohort Study From Latin America.

Background: Children with cancer are at risk of critical disease and mortality from COVID-19 infection. In this study, we describe the clinical characteristics of pediatric patients with cancer and COVID-19 from multiple Latin American centers and risk factors associated with mortality in this population. Methods: This study is a multicenter, prospective cohort study conducted at 12 hospitals from 6 Latin American countries (Argentina, Bolivia, Colombia, Ecuador, Honduras and Peru) from April to November 2021. Patients younger than 14 years of age that had an oncological diagnosis and COVID-19 or multisystemic inflammatory syndrome in children (MIS-C) who were treated in the inpatient setting were included. The primary exposure was the diagnosis and treatment status, and the primary outcome was mortality. We defined "new diagnosis" as patients with no previous diagnosis of cancer, "established diagnosis" as patients with cancer and ongoing treatment and "relapse" as patients with cancer and ongoing treatment that had a prior cancer-free period. A frequentist analysis was performed including a multivariate logistic regression for mortality. Results: Two hundred and ten patients were included in the study; 30 (14%) died during the study period and 67% of patients who died were admitted to critical care. Demographics were similar in survivors and non-survivors. Patients with low weight for age (<-2SD) had higher mortality (28 vs. 3%, p = 0.019). There was statistically significant difference of mortality between patients with new diagnosis (36.7%), established diagnosis (1.4%) and relapse (60%), (p <0.001). Most patients had hematological cancers (69%) and they had higher mortality (18%) compared to solid tumors (6%, p= 0.032). Patients with concomitant bacterial infections had higher mortality (40%, p = 0.001). MIS-C, respiratory distress, cardiovascular symptoms, altered mental status and acute kidney injury on admission were associated with higher mortality. Acidosis, hypoxemia, lymphocytosis, severe neutropenia, anemia and thrombocytopenia on admission were also associated with mortality. A multivariate logistic regression showed risk factors associated with mortality: concomitant bacterial infection OR 3 95%CI (1.1-8.5), respiratory symptoms OR 5.7 95%CI (1.7-19.4), cardiovascular OR 5.2 95%CI (1.2-14.2), new cancer diagnosis OR 12 95%CI (1.3-102) and relapse OR 25 95%CI (2.9-214). Conclusion: Our study shows that pediatric patients with new onset diagnosis of cancer and patients with relapse have higher odds of all-cause mortality in the setting of COVID-19. This information would help develop an early identification of patients with cancer and COVID-19 with higher risk of mortality.

Mortality in children with cancer and SARS-CoV-2 in Latin America: A systematic review.

The new COVID-19 disease is caused by a novel coronavirus (SARS-CoV-2), that probably originated in Wuhan, China, and has currently infected 505,817,953 people and caused 6,213,876 deaths in the world. On the American continent, 152,265,980 cases and 2,717,108 deaths have been reported to WHO (World Health Organization). The Latin America and the Caribbean (LAC) region presents an epidemiological challenge due to its population's heterogeneity and socioeconomic inequality. A particularly vulnerable population is that of children with cancer, and their mortality from COVID-19 has been reported to be 3.6% globally. This work aimed to study the lethality of SARS-CoV-2 infection in children with cancer in the Latin American region. Our objective was to systematically review published scientific literature and search hospital databases in Latin America to explore mortality in this region. A median of mortality of 9.8% was found in the articles analyzed. In addition, we collected five databases from Latin American hospitals. We concluded that there was an underestimation in the mortality registry of this group of patients in the analyzed region. Therefore, although the causes are unknown, it is necessary to strengthen the case-reporting system to determine the reality in complex and particular areas such as Latin America.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

Systemic lupus erythematosus complicated with macrophage activation syndrome mimicking COVID-19 multisystemic inflammatory syndrome in children.

BACKGROUND: Macrophage activation syndrome (MAS) is characterized by excessive activation of macrophages and lymphocytes, leading to multiorgan dysfunction. As the initial manifestation of systemic lupus erythematosus (SLE), MAS is rare in children. Due to the COVID-19 pandemic, it is vital to identify the MAS as it shares similar characteristics with the multisystem inflammatory syndrome in children (MIS-C). CASE REPORT: We report the case of an 11-year-old male adolescent with symptoms of MIS-C. Although with negative results of RT-PCR (reverse transcription-polymerase chain reaction) and serology for SARS-CoV-2, contact with a positive COVID-19 relative was reported. When admitted to a referral hospital center, the patient received standard treatment for MIS-C. Although the same scheme was given on three occasions, the patient showed no response to initial therapy. Thus, the patient was classified as a refractory case. When the study was extended to other differential diagnoses, we found MAS associated with SLE. Therefore, the patient was treated with etoposide, cyclosporine, dexamethasone, and methotrexate and showed a good clinical response. CONCLUSIONS: MAS associated with SLE is rare in the pediatric population. MAS shares inflammatory markers with the MIS-C and is often confused with rheumatologic, infectious, and neoplastic entities. Reporting this case is important to identify differential diagnoses in patients presenting as MIS-C and decide on timely treatment, as it could be harmful or even fatal if a definitive diagnosis is not obtained on time.

INTRODUCCIÓN: El síndrome de activación de macrófagos (SAM) se caracteriza por una activación excesiva de los macrófagos y de los linfocitos que conduce a una disfunción multiorgánica. Como manifestación inicial del lupus eritematoso sistémico (LES), el SAM es poco común en la infancia. Debido a la pandemia de COVID-19, es importante identificar el SAM, ya que comparte características similares con el síndrome inflamatorio multisistémico en niños (MIS-C, por sus siglas en inglés). CASO CLÍNICO: Presentamos el caso de un varón de 11 años con síntomas de MIS-C. Resultó negativo en la prueba de reacción en cadena de la polimerasa con retrotranscriptasa y en la serología para SARS-CoV-2, aunque reportó contacto con un familiar positivo para COVID-19. Ingresó en un centro hospitalario de referencia y recibió tratamiento estandarizado para MIS-C. A pesar de recibir el mismo esquema en tres ocasiones, no mostró respuesta a la terapia inicial, por lo que fue clasificado como caso refractario. Al ampliar el estudio para otros diferenciales, se encontró SAM asociado con LES, por lo que el paciente recibió tratamiento con etopósido, ciclosporina, dexametasona y metotrexato, y mostró buena respuesta clínica. CONCLUSIONES: La asociación entre el SAM y el LES es rara en la población pediátrica. El SAM comparte marcadores inflamatorios con el MIS-C y suele confundirse con enfermedades reumatológicas, infecciosas y neoplásicas. La importancia de reportar este caso es identificar los diagnósticos diferenciales en los pacientes que se presentan como MIS-C, y decidir el tratamiento con prontitud, pues podría ser dañino o incluso fatal si no se obtiene un diagnóstico definitivo a tiempo.

Persistent COVID-19 lung infection in a child with a primary immunodeficiency.

SARS-CoV-2 infection in children with primary immunodeficiency disease (PID) and its complications have not yet been well described, the course of COVID-19 can range from mild illness to death. We aim to report the case of a child with a PID who develop a severe and persistent pulmonary COVID-19 infection. We present chronologically his clinical course, tests, interventions and radiological findings showing his irregular evolution and poor response to infection. This case highlights the need to accurately monitor the immune response in these cases to try to stop the progression of the damage.