Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection.

To date, the SARS-CoV-2 pandemic still represents a great clinical challenge worldwide, and effective anti-COVID-19 drugs are limited. For this reason, nutritional supplements have been investigated as adjuvant therapeutic approaches in disease management. Among such supplements, vitamin D has gained great interest, due to its immunomodulatory and anti-inflammatory actions both in adult and pediatric populations. Even if there is conflicting evidence about its prevention and/or mitigation effectiveness in SARS-CoV-2 infection, several studies demonstrated a strict correlation between hypovitaminosis D and disease severity in acute COVID-19 and MIS-C (multisystem inflammatory syndrome in children). This narrative review offers a resume of the state of the art about vitamin D's role in immunity and its clinical use in the context of the current pandemic, specially focusing on pediatric manifestations and MIS-C. It seems biologically reasonable that interventions aimed at normalizing circulating vitamin D levels could be beneficial. To help clinicians in establishing the correct prophylaxis and/or supportive therapy with vitamin D, well-designed and adequately statistically powered clinical trials involving both adult and pediatric populations are needed. Moreover, this review will also discuss the few other nutraceuticals evaluated in this context.

Multiple dental caries management of a 5-year-old child with MIS-C: a case report.

The rare hyper-inflammatory condition known as "multisystem inflammatory syndrome in children (MIS-C)" develops after a COVID-19 infection. Providing dental treatment for patients with MIS-C can be very challenging due to the immunocompromised condition found in these patients leading to rapid progression of other infections, including dental caries. Currently, there is a lack of information regarding the dental management of patients with MIS-C. This case report presents the multiple dental caries management in a 5-year-old Cambodian boy with MIS-C in a dental chair unit, without general anesthesia. Despite the challenges this case presented, i.e., the patient's age, hyper-inflammatory condition due to MIS-C, taking several medications, multiple caries lesions, and the language barrier for behavior management, we were able to meet this patient's needs. The patient's dental and physical health were found to be satisfactorily stable with no complications. At the 6-month recall, his overall oral health had dramatically improved. Careful treatment planning along with a multidisciplinary approach is highly recommended in such cases. The important roles of dentists are not only to treat oral infection, but also to approach patients holistically because the body systems are all connected.

Assessment of trace elements in critically ill patients with systemic inflammatory response syndrome: A systematic review.

BACKGROUND: Zinc (Zn), copper (Cu), and selenium (Se) are involved in immune and antioxidant defense. Their role in systemic inflammatory response syndrome (SIRS) treatment and outcomes remains unclear. This systematic review aimed to describe trace element concentrations in different types of biological samples and their relationship with morbidity and mortality in patients with SIRS. METHODS: Literature was systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The search results were screened and evaluated for eligibility, and data were extracted and summarized in tables and figures. RESULTS: Most of the 38 included studies evaluated Se (75%), followed by Zn (42%) and Cu (22%). Plasma was the main biological sample evaluated (58%). Thirteen studies found lower plasma/serum concentrations of Zn, Se, and Cu in SIRS patients than in controls upon admission, 11 studies on adults (intensive care unit-ICU) and two in pediatric ICU (PICU). Three ICU studies found no difference in erythrocyte trace element concentrations in patients with SIRS. In all studies, the two main outcomes investigated were organ failure and mortality. In seven ICU studies, patients with lower plasma or serum Zn/Se levels had higher mortality rates. A study conducted in the PICU reported an association between increased Se variation and lower 28-day mortality. In an ICU study, lower erythrocyte selenium levels were associated with higher ICU/hospital mortality, after adjustment. Five ICU studies associated lower plasma/serum Zn/Se levels with higher organ failure scores and one PICU study showed an association between higher erythrocyte Se levels and lower organ dysfunction scores. CONCLUSION: There was no difference in erythrocyte Se levels in patients with SIRS. Serum/Plasma Zn and serum/plasma/erythrocyte Se are associated with organ dysfunction, mortality, and inflammation. Trace element deficiencies should be diagnosed by erythrocyte, or complementary measurements in the presence of inflammation.

The prediction of lymphocyte count and neutrophil count on the efficacy of Xuebijing adjuvant treatment for severe community-acquired pneumonia: A post hoc analysis of a randomized controlled trial.

BACKGROUND: Adjuvant Xuebijing therapy exhibited a protective effect on severe community-acquired pneumonia (SCAP) in previous studies. Blood inflammatory biomarkers related to the disease subtype and severity of SCAP might be associated with the effects of Xuebijing on clinical outcomes of SCAP. PURPOSE: To investigate whether neutrophils or lymphocytes are a useful biomarker of the therapeutic effect of Xuebijing on mortality and inflammation damage index. STUDY DESIGN: A post hoc analysis of a randomized, placebo-controlled and double-blinded clinical trial of Xuebijing in patients with SCAP (Clinical Trial Registration: ChiCTR-TRC-13003534). METHODS: We compared 28-day mortality (primary outcome) and four clinical scores (secondary outcome), including pneumonia severity index (PSI) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, and systemic inflammatory response syndrome (SIRS) score, according to the baseline strata of neutrophil count and lymphocyte count. RESULTS: A total of 675 patients were included in the analyses, of which 334 received Xuebijing and 341 received the placebo. Xuebijing was more effective in SCAP patients with higher lymphocyte counts and lower neutrophil counts. In the lymphocyte-dominated inflammation (LDI) subgroup, defined as neutrophil count <13 × 109 cells/l and lymphocyte count ≥0.65 × 109 cells/l, Xuebijing reduced 28-day mortality by 15% while mortality of the neutrophil-dominated inflammation (NDI) subgroup decreased by 4.7% (p = 0.050). There was also greater improvement in the PSI, SOFA, APACHE II, and SIRS scores following Xuebijing treatment in the LDI subgroup compared with the NDI subgroup. CONCLUSIONS: Xuebijing treatment shows stronger protective effects in SCAP patients with higher lymphocyte and lower neutrophil counts. Our findings may facilitate the selection of the most appropriate treatments for individual patients with SCAP, including who will receive Xuebijing injections.

Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury viathe NF-κB/NLRP3 pathway.

Sepsis-induced uncontrolled systemic inflammatory response syndrome (SIRS) is a critical cause of multiple organ failure. Acute kidney injury (AKI) is one of the most serious complications associated with an extremely high mortality rate in SIRS, and it lacked simple, safe, and effective treatment strategies. Leontopodium leontopodioides (Willd.) Beauv (LLB) is commonly used in traditional Chinese medicine for the treatment of acute and chronic nephritis. However, it remains unclear whether lipopolysaccharide (LPS) affects LPS-induced AKI. To identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice, LLB was prepared by extraction with 70% methanol, while a lipopolysaccharide (LPS)-induced HK-2 cell model and an AKI model were established in this study. Renal histopathology staining was performed to observe the morphology changes. The cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA, immunofluorescence, and Western blot. The results indicated that LLB significantly reduced the expression of IL-6 and TNF-α in LPS-induced HK-2 cells, as well as the secretion of IL-6, TNF-α, and IL-1ß in the supernatant. The same results were observed in LPS-induced AKI serum. Further studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA, SOD, and CAT in serum and TUNEL staining results. Notably, LLB significantly reduced the mortality due to LPS infection. Renal histopathology staining results supported these results. Furthermore, immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3, ASC, and Caspase-1 which were significantly increased through LPS stimulation. These findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

TCM and Western Medicine: Diagnosis and Treatment of Novel Coronavirus Pneumonia, A Case Study.

Context: Clinical-practice observations have revealed that novel coronavirus pneumonia is related to the dampness pathogen; most patients show a systemic inflammatory response syndrome (SIRS), and patients with a severe form of the disease have sepsis. Objective: The current study aimed to explore the role of Traditional Chinese medicine (TCM) and western medicine in the treatment of COVID-19. Design: The research team developed a case study. Setting: The study took place at the Nanchang Ninth Hospital in Nanchang, China. Participant: The participant was a 44-year-old female patient with diabetes who was a hepatitis B carrier. She was admitted to the hospital and diagnosed with novel coronavirus pneumonia at admission. Intervention: She was treated for seven days with Western medicine, at which time the nucleic acid test for the virus was negative; however, she still had flaky glass shadows in the lungs. She was then treated with TCM. Results: The patient reached the discharge standard on February 29. A recheck was performed on March 6, six days after discharge. Her chest CT showed that the two lung lesions continued to be absorbed, and the viral nucleic acid test was negative. Conclusions: For diagnosis and treatment of novel coronavirus pneumonia, the determination of the use of six channels or Wei-qi-Ying-blood differentiation needs to be combined with syndrome differentiation and to comply with the body's process of eliminating pathogens. The recovery of qi, blood and body fluid, and SIRS should be taken into account.

Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury viathe NF-κB/NLRP3 pathway / 中国天然药物

Sepsis-induced uncontrolled systemic inflammatory response syndrome (SIRS) is a critical cause of multiple organ failure. Acute kidney injury (AKI) is one of the most serious complications associated with an extremely high mortality rate in SIRS, and it lacked simple, safe, and effective treatment strategies. Leontopodium leontopodioides (Willd.) Beauv (LLB) is commonly used in traditional Chinese medicine for the treatment of acute and chronic nephritis. However, it remains unclear whether lipopolysaccharide (LPS) affects LPS-induced AKI. To identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice, LLB was prepared by extraction with 70% methanol, while a lipopolysaccharide (LPS)-induced HK-2 cell model and an AKI model were established in this study. Renal histopathology staining was performed to observe the morphology changes. The cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA, immunofluorescence, and Western blot. The results indicated that LLB significantly reduced the expression of IL-6 and TNF-α in LPS-induced HK-2 cells, as well as the secretion of IL-6, TNF-α, and IL-1β in the supernatant. The same results were observed in LPS-induced AKI serum. Further studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA, SOD, and CAT in serum and TUNEL staining results. Notably, LLB significantly reduced the mortality due to LPS infection. Renal histopathology staining results supported these results. Furthermore, immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3, ASC, and Caspase-1 which were significantly increased through LPS stimulation. These findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

Erythrocyte and plasma selenium in children with acute inflammatory response.

OBJECTIVES: Plasma selenium may not reflect selenium status in critically ill patients because it transiently decreases inversely with the magnitude of the systemic inflammatory response. The decision to supplement selenium should ideally be based on laboratory measurements that reliably reflect selenium status. We hypothesized that erythrocyte selenium, unlike plasma selenium, is not affected by the systemic inflammatory response in critically ill children. METHODS: In a prospective study of 109 critically ill children, plasma and erythrocyte selenium concentrations were evaluated on admission, and plasma selenoprotein P was evaluated on days 1, 2, and 3 of the ICU stay. The main outcome was the effect of systemic inflammation on the erythrocyte and plasma selenium concentrations. The magnitude of the systemic inflammatory response was measured using serum C-reactive protein (CRP) and procalcitonin levels. The covariates were age, sex, anthropometric nutritional status, diagnosis of severe sepsis/septic shock, and clinical severity on admission. Multiple linear regression and generalized estimating equations were used for statistical analysis. RESULTS: Erythrocyte selenium levels were not influenced by the magnitude of the inflammatory response or by the patient's clinical severity. Procalcitonin (ß coefficient=-0.99; 95%CI: -1.64; -0.34, p = 0.003) and clinical severity (ß coefficient= -11.13; 95%CI: -21.6; -0.63), p = 0.038) on admission were associated with decreased plasma selenium concentrations. Erythrocyte selenium was associated with selenoprotein P in the first three days of ICU stay (ß coefficient=0.32; 95%CI: 0.20; 0.44, p < 0.001). CONCLUSION: Unlike plasma selenium, erythrocyte selenium does not change in children with an acute systemic inflammatory response and is associated with selenoprotein P concentrations. Erythrocyte selenium is probably a more reliable marker than plasma selenium for evaluating the selenium status in critically ill children.

Vitamin D Status in Critically Ill Patients with SIRS and Its Relationship with Circulating Zn and Related Parameters during ICU Stay.

Critically ill patients are exposed to different stressors which may generate Systemic Inflammatory Response Syndrome (SIRS). This situation hinders the assessment of micronutrients status, such as vitamin D or Zinc (Zn), potentially affecting patients' treatment and recovery. The aim of the present study was to assess the evolution of circulating 25-Hydroxyvitamin D (25-OH-D) levels after seven days of Intensive Care Unit (ICU) stay and the influence on changes in plasma and erythrocyte Zn levels, as well as other parameters related to phosphorus-calcium metabolism. A prospective analytical study was conducted on 65 critically ill patients (42% women) aged 31-77 years with SIRS. Total 25-OH-D levels were measured in plasma samples by liquid chromatography-tandem mass spectrometry, and Zn content was analyzed by flame atomic absorption spectrometry. Both 25-OH-D and 25-OH-D3 levels were directly associated with erythrocyte Zn concentration at follow-up (p = 0.046 and p = 0.011, respectively). A relationship between erythrocyte and plasma Zn was also found at this follow-up point. No such clear associations were found when considering 25-OH-D2. Different disturbances in levels of phosphorus-calcium metabolism parameters were found, suggesting a relationship between the changes of 25-OH-D3 levels and parathormone (p = 0.019) and phosphorus (p = 0.005). The findings of the present study suggest an interaction between vitamin D and Zn, in which the correct status of these micronutrients could be a potentially modifiable factor and a beneficial approach in the recovery of critically ill patients.

Oral supplementation with Lithothamnion extract in horses subjected to oligofructose overload intake: effects on systemic inflammation and multiple organ function.

Systemic inflammatory response syndrome (SIRS) is a common condition in horses with gastrointestinal disorders. If not prevented or controlled, SIRS promotes multiple organ dysfunctions that may culminate in serious disabilities or even death. The objective of this study was to evaluate the effects of Lithothamnion supplementation on systemic inflammatory response and organ function variables in horses undergoing oligofructose overload (OFO) intake. Twelve healthy horses were randomly divided into control and treated groups. The treated group received Lithothamnion (100 mg/kg bw PO BID) for 7 days before oligofructose intake (10 g/kg PO). Horses underwent clinical and laboratory evaluation immediately before and 6, 12, 18, and 24 h following administration of oligofructose. Parametric data were subjected to ANOVA in randomized blocks, followed by Tukey, and Student's t-tests for mean comparsions. Non-parametric data were analyzed by the Friedman, Dunn's, and Mann-Whitney tests (P < .05). Systemic inflammation and organ dysfunction was evident in both groups; however, these changes were milder and delayed in the treated group. Supplementation attenuated and delayed the tachycardia, tachypnea, leukocytosis, hyperproteinemia, hyperbilirubinemia, hyperalbuminemia and hyperglycemia in treated horses undergoing OFO. Furthermore, increases in packed cell volume, red blood cells, hemoglobin, globulin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, indirect and direct bilirubin and creatinine were observed only in the control group, remaining unchanged in the treated group. These findings demonstrate the potential of oral supplementation with Lithothamnion to ameliorate systemic inflammation and organ dysfunction in horses at risk of acquiring gastrointestinal disorders.

Long COVID in Children and Adolescents.

Objective: To review the empirical evidence regarding neuropsychiatric illness (long coronavirus disease [COVID]) in children and adolescents post-severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection.Data Sources: A search of PubMed, PsycINFO, Cochrane Library, and Google Scholar was conducted from the date of inception until February 2022 using the keywords corona*, COVID-19, SARS-CoV-2, mental health, depression, anxiety, neurological, psychiatric, long COVID, and post-COVID outcomes. Age filters were used to include children and adolescents aged ≤ 18 years.Study Selection: The search resulted in the identification of 526 articles; 48 articles met the inclusion criteria.Data Extraction: Results are presented using a narrative review format. Data regarding long COVID in children and adolescents post-SARS-CoV-2 infection were extracted to understand epidemiologic trends, preventive measures, and treatment options.Results: Studies during the initial phase of the pandemic reported a mixed range of symptoms from case reports or case series. However, multisystem inflammatory syndrome in children (MIS-C) was widely reported. During the subsequent phases, the emergence of new variants led to a surge of SARS-CoV-2 infections in pediatric populations. There were highly variable, mixed symptom clusters within 60 days post-infection, which resolved in many patients within 6 months. There were prolonged illnesses and impairments in some children and adolescents with long COVID, and many had similar symptoms even though they tested negative for COVID-19.Conclusions: Long COVID symptoms are both physical and mental in nature among children and adolescents. The impairments have the potential to affect long-term functioning and increase the overall burden on health care delivery. Despite current studies having methodological issues, there is a consensus to provide multidisciplinary and holistic care to those in need.

Association of selenium status with endothelial activation during acute systemic inflammation in children.

BACKGROUND & AIMS: Evidence that selenium has a role in endothelial function comes mainly from experimental research, but few clinical studies have examined the pathophysiology of selenium in endothelial activation. We aimed to investigate whether there are associations between selenium status and the magnitude of endothelial activation and the severity of multiple organ dysfunction during the acute phase of systemic inflammatory response syndrome (SIRS) in children. METHODS: A prospective cohort study was carried out in 109 children with SIRS admitted to a pediatric ICU (PICU). Erythrocyte and plasma selenium were measured on admission and selenoprotein P and soluble plasma forms of the intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), sP-selectin, and endoCAM on days 1, 2 and 3 of hospitalization. Generalized estimating equations models were adjusted for clinical severity parameters, C-reactive protein, procalcitonin, and serum lactate. The effect of selenium status on organ dysfunction was defined by the Pediatric Logistic Organic Dysfunction (PELOD-2) during the PICU stay. RESULTS: Erythrocyte selenium was associated with sP-selectin and endoCAM, but not with ICAM-1 and VCAM-2. An increase of 10 µg/L in erythrocyte selenium resulted in increases of 43.2 ng/mL (p = 0.001) in sP-selectin and of 0.04 ng/mL (p < 0.001) in endoCAM. Erythrocyte selenium was also associated with a decrease in PELOD-2 (p = 0.015). Plasma selenium was not related to any of the outcomes. CONCLUSIONS: Erythrocyte selenium is associated with endothelial activation in the early phase of the systemic inflammatory response in children, and has a protective effect on multiple organ dysfunction during their PICU stay. Registered at: www.clinicaltrials.gov (NCT00708799).

Optimized Curcumin, Pomegranate Extract, and Methylsulfonylmethane Reduce Acute, Systemic Inflammatory Response to a Half-marathon Race.

Context: Endurance running places substantial physiological strain on the body, which can develop into chronic inflammation and overuse injuries, negatively affecting subsequent training and performance. A recent study found that dietary polyphenols and methlysulfonylmethane (MSM) can reduce systemic inflammation and oxidative stress without adverse side effects. Objective: The purpose was to identify a set of candidate protein and RNA biomarkers that are associated with improved outcomes related to inflammation and muscle injury, when athletes used 3 proprietary supplements both prior to and during early recovery from a half-marathon race. Design: The study was an open-label pilot study. Setting: The study was field based, with sample analysis conducted in the Applied Physiology Laboratory in the Department of Kinesiology, Health Promotion and Recreation at the University of North Texas in Denton, Texas. Participants: Participants were 15 young, exercise-trained men and women. Intervention: The intervention group consumed 1000 mg/d of a proprietary 50-50 mix of optimized curcumin and pomegranate extract for 26 days. The group also consumed 500 mg/d of a proprietary MSM for the same period. Three days prior to and one day after a race, the daily dosage was doubled. The control group received no supplements. Outcome Measures: Venous blood samples were collected at pre-race and at 4h and 24h after running a half-marathon race. The research team evaluated results for target proteins that have been associated with inflammation and muscle injury in the scientific literature. The team also performed an analysis of RNA biomarkers. Results: At the 4h and 24h time points, a significant treatment-response was observed that included increases in proteins: (1) osteonectin/SPARC-osteonectin/secreted protein acidic and rich in cysteine and (2) BDNF-brain-derived neurotrophic factor. At the same points, the study also found increased RNA: (1) PACER-P50-associated COX-2 extragenic RNA, (2) PTGES-prostaglandin E synthase, (3) MYD88-innate immune signal transduction adaptor MYD88, (4) TNFS14-tumor necrosis factor (TNF) superfamily member 14, (5) THRIL-TNF and heterogeneous nuclear ribonucleoprotein L (HNRNPL)-related immunoregulatory long noncoding RNA, (6) TRAF6-TNF receptor associated factor 6, (7) CX3CL1-C-X3-C motif chemokine ligand 1, (8) MALAT1-metastasis-associated lung adenocarcinoma transcript 1, and (9) LINC00305-long intergenic nonprotein coding RNA 305. Conclusions: The combination of polyphenol and MSM supplementation resulted in a systemic response that may translate to an accelerated rate of muscle recovery, allowing participants return to exercise and normal activities more quickly. This pilot study is the foundation for a larger investigation in the research team's laboratory.

Transcutaneous vagal nerve simulation to reduce a systemic inflammatory response syndrome and the associated intestinal failure: study protocol of a prospective, two-armed, sham-controlled, double-blinded trial in healthy subjects (the NeuroSIRS-Study).

PURPOSE: Surgery initiates pro-inflammatory mediator cascades leading to a variably pronounced sterile inflammation (SIRS). SIRS is associated with intestinal paralysis and breakdown of intestinal barrier and might result in abdominal sepsis. Technological progress led to the development of a neurostimulator for transcutaneous auricular vagal nerve stimulation (taVNS), which is associated with a decline in inflammatory parameters and peristalsis improvement in rodents and healthy subjects via activation of the cholinergic anti-inflammatory pathway. Therefore, taVNS might be a strategy for SIRS prophylaxis. METHODS: The NeuroSIRS-Study is a prospective, randomized two-armed, sham-controlled, double-blind clinical trial. The study is registered at DRKS00016892 (09.07.2020). A controlled endotoxemia is used as a SIRS-mimicking model. 2 ng/kg bodyweight lipopolysaccharide (LPS) will be administered after taVNS or sham stimulation. The primary objective is a reduction of clinical symptoms of SIRS after taVNS compared to sham stimulation. Effects of taVNS on release of inflammatory cytokines, intestinal function, and vital parameters will be analyzed. DISCUSSION: TaVNS is well-tolerated, with little to no side effects. Despite not fully mimicking postoperative inflammation, LPS challenge is the most used experimental tool to imitate SIRS and offers standardization and reproducibility. The restriction to healthy male volunteers exerts a certain bias limiting generalizability to the surgical population. Still, this pilot study aims to give first insights into taVNS as a prophylactic treatment in postoperative inflammation to pave the way for further clinical trials in patients at risk for SIRS. This would have major implications for future therapeutic approaches.

Síndrome inflamatória multissistêmica pediátrica enquanto complicação da covid-19 e um desafio para médicos: revisão integrativa / Pediatric multisystemic inflammatory syndrome as a complication for covid-19 and a challenge for medical professional: integrative review / El síndrome inflamatorio multisistémico pediátrico como complicación posible delcovid-19 y desafío para los médicos: revisión integrativa

Introdução:A Síndrome Inflamatória MultissistêmicaPediátrica corresponde a uma entidade clínica rara e potencialmente fatal. Objetivo:Avaliar a síndrome como uma provável complicação da COVID-19 em crianças e compreender os desafios clínicos e terapêuticos dos médicos de frente ao agravo.Metodologia:Revisão integrativa da literatura, realizada em seis fases. Foi feita uma busca bibliográfica de evidências nas bases de dados eletrônicos da Scientific Electronic Library Online e na Public Medline or Publisher Medline, utilizandocomo descritores "Multisystem inflammatory syndrome" AND "child" AND "Coronavirus infections".A população de estudo é formada porpacientes menoresde 18 anos de idade que apresentaram relação com a COVID-19 e o desenvolvimento da síndrome. Foram usadoscomo critérios de inclusão estudos na formatação de artigos, textos completos gratuitos e idioma (inglês e português). Já os critérios de exclusão adotados foram: Estudosque não respondiam aos objetivos da pesquisa. Os artigosselecionados foram analisados criteriosamente pelos pesquisadores em busca de informações sobre a relação entre essas patologias e osdesafios dos médicos diante do agravo.Resultados:Após análise dos 14 artigos selecionados, observou-se que os sintomas mais relatados pelos autores foram: febre (100%), problemas gastrointestinais (92,8%), disfunção cardíaca (100%), manifestações mucocutânea (100%) e a idade média de acometimento foi 6-10 anos (64,3%). Quanto ao tratamento, 100%dos estudos relataram a necessidade de hospitalização e referiram que a administração de imunoglobulina intravenosa é uma ótima opção terapêutica.Conclusões:A Síndrome Inflamatória Multissistêmica Pediátricaapresenta uma associação temporal, geográficae laboratorial com a COVID-19, sendo considerada uma possível complicação. Essa nova entidade clínica é um desafio para os médicos por apresentar umespectro clínico diverso, quanto ao tratamento aindaé necessário mais estudos objetivandodeterminar um tratamento específico para a doençacapaz de reduzir sua mortalidade (AU).

Introduction:Pediatric Multisystem Inflammatory Syndrome is a rare and potentially fatal clinical entity. Objective:To evaluate the syndromeas a likely complication of COVID-19 in children and to understand the clinical and therapeutic challenges faced by physicians in this syndrome. Methodology:Integrative literature review, carried out in six phases. A bibliographic search of evidence was performed in the electronic databases of Scientific Electronic Library Online and in Public Medline or Publisher Medline, using as descriptors "Multisystem inflammatory syndrome" AND "child" AND "Coronavirus infections". The study population consists of patients under 18 years of age who were related to COVID-19 and the development of the syndrome.Studies in the formatting of articles, free full texts and language (English and Portuguese) were used as inclusion criteria. The exclusion criteria adopted were: Studies that did not meet the research objectives. The selected articles were carefully analyzed by the researchers in search of information on the relationship between these pathologies and the challenges faced by physicians in the face of the problem. Results:After analyzing the 14 selected articles, it was observed that the symptoms most reported by the authors were: fever (100%), gastrointestinal problems (92.8%), cardiac dysfunction (100%), mucocutaneous manifestations (100%) and the mean age of onset was 6-10 years (64.3%). As for treatment, 100% of the studies reported the need for hospitalization and reported that the administration of intravenous immunoglobulin is an excellent therapeutic option. Conclusions:The Pediatric Multisystem Inflammatory Syndrome has a temporal, geographic and laboratory association with COVID-19, being considered a possible complication. This new clinical entity is a challenge for physicians because it has a diverse clinical spectrum, as for the treatment, more studies are needed in order to determine a specific treatment for the disease capable of reducing itsmortality (AU).

Introducción: El Síndrome Inflamatorio Multisistémico Pediátrico corresponde a una entidad clínica rara y potencialmente fatal. Objetivo: Evaluar el síndrome como una posible complicación del COVID-19 en niños y comprender los desafíos clínicos y terapéuticos que enfrentan los médicos en este síndrome. Metodología: Revisión integrativa de la literatura, realizada en seis fases. Se realizó una búsqueda bibliográfica de evidencias en las bases de datos electrónicas de Scientific Electronic Library Online y en Public Medline o Publisher Medline, utilizando como descriptores "Multisystem inflammatory syndrome" AND "child" AND "Coronavirus infections". La población de estudio está formada por pacientes menores de 18 años que se relacionaron con COVID-19 y el desarrollo del síndrome. Se utilizaron como criterios de inclusión estudios sobre el formato de los artículos, los textos completos libres y el idioma (inglés y portugués). Los criterios de exclusión fueron: Estudios que no cumplieron con los objetivos de la investigación. Los artículos seleccionados fueron cuidadosamente analizados por los investigadores en busca de información sobre la relación entre estas patologías y los desafíos que enfrentan los médicos ante el problema.Resultados: Tras analizar los 14 artículos seleccionados, se observó que los síntomas más reportados por los autores: fiebre (100%), problemas gastrointestinales (92,8%),disfunción cardíaca (100%), manifestaciones mucocutáneas (100%) y la edad media de aparición fue de 6 a 10 años (64,3%). En cuanto al tratamiento, el 100% de los estudios reportaron la necesidad de hospitalización y reportaron que la administración de inmunoglobulina intravenosa es una excelente opción terapéutica. Conclusiones: El Síndrome Inflamatorio Multisistémico Pediátrico tiene asociación temporal, geográfica y de laboratorio con COVID-19, considerándose una posible complicación. Esta nueva entidad clínica es un desafío para los médicos porque tiene un espectro clínico diverso, en cuanto al tratamiento, se necesitan más estudios para determinar un tratamiento específico para la enfermedad capaz de reducir su mortalidad (AU).

The first 1000 symptomatic pediatric SARS-CoV-2 infections in an integrated health care system: a prospective cohort study.

BACKGROUND: The spectrum of illness and predictors of severity among children with SARS-CoV-2 infection are incompletely understood. METHODS: Active surveillance was performed for SARS-CoV-2 by polymerase chain reaction among symptomatic pediatric patients in a quaternary care academic hospital laboratory beginning March 12, 2020. We obtained sociodemographic and clinical data 5 (+/-3) and 30 days after diagnosis via phone follow-up and medical record review. Logistic regression was used to assess predictors of hospitalization. RESULTS: The first 1000 symptomatic pediatric patients were diagnosed in our institution between March 13, 2020 and September 28, 2020. Cough (52 %), headache (43 %), and sore throat (36 %) were the most common symptoms. Forty-one (4 %) were hospitalized; 8 required ICU admission, and 2 required mechanical ventilation (< 1 %). One patient developed multisystem inflammatory syndrome in children; one death was possibly associated with SARS-CoV-2 infection. Symptom resolution occurred by follow-up day 5 in 398/892 (45 %) patients and by day 30 in 443/471 (94 %) patients. Pre-existing medical condition (OR 7.7; 95 % CI 3.9-16.0), dyspnea (OR 6.8; 95 % CI 3.2-14.1), Black race or Hispanic ethnicity (OR 2.7; 95 % CI 1.3-5.5), and vomiting (OR 5.4; 95 % CI 1.2-20.6) were the strongest predictors of hospitalization. The model displayed excellent discriminative ability (AUC = 0.82, 95 % CI 0.76-0.88, Brier score = 0.03). CONCLUSIONS: In 1000 pediatric patients with systematic follow-up, most SARS-CoV-2 infections were mild, brief, and rarely required hospitalization. Pediatric predictors of hospitalization included comorbid conditions, Black race, Hispanic ethnicity, dyspnea and vomiting and were distinct from those reported among adults.

[Systematic review and sequential analysis of Xuebijing Injection in treatment of systemic inflammatory response syndrome].

To systematically review the efficacy of Xuebijing Injection combined with western medicine in the treatment of systemic inflammatory response syndrome(SIRS). In this study, CBM, CNKI, Wanfang, VIP, PubMed and EMbase databases were retrieved for clinical randomized controlled trials on the effect of Xuebijing Injection combined with western medicine in the treatment of SIRS from the establishment of the database to July 31, 2020. After screening, Meta-analysis was conducted by RevMan 5.3 software, trial sequential analysis was conducted by TSA 0.9.5.10 beta software, and the evidence quality level was evaluated by GRADEprofiler 3.6.1 software. Meta-analysis showed that Xuebijing Injection combined with western medicine could reduce white blood cell count(MD=-2.32, 95%CI[-2.44,-2.21], P<0.000 01), C-reactive protein count(MD=-22.70, 95%CI[-29.61,-15.79], P<0.000 01), APACHE Ⅱ score(MD=-2.15, 95%CI[-2.43,-1.87], P<0.000 01), tumor necrosis factor alpha count(SMD=-1.23, 95%CI[-1.48,-0.99], P<0.000 01) and interleukin-6 count(SMD=-0.92, 95%CI[-1.15,-0.69], P<0.000 01), improve treatment efficiency(RR=1.39, 95%CI[1.23, 1.56], P<0.000 01), reduce incidence of multiple organ dysfunction(RR=0.47, 95%CI[0.35, 0.64], P<0.000 01) and mortality(RR=0.22, 95%CI[0.13, 0.37], P<0.000 01), which were better than western medicine treatment alone. Trial sequential analysis showed that in terms of reducing the incidence of multiple organ dysfunction and C-reactive protein count, the cumulative Z value passed through the traditional threshold, TSA threshold and expected information value, and reached the required number of cases. GRADE evaluation showed that the level of evidence was low or very low. According to the findings, Xuebijing Injection combined with western medicine is effective in treating SIRS. However, as the low quality of the included studies may affect the reliability of the conclusion, more high-quality studies shall be included for further verification in the future, so as to provide better suggestions for clinical medication.

IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine whether plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a core inflammatory signature of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Fifteen of 135 analytes were significantly different in HLH plasma compared with SIRS/sepsis, including increased interferon-γ (IFN-γ)-regulated chemokines CXCL9, CXCL10, and CXCL11. Furthermore, a 2-analyte plasma protein classifier including CXCL9 and interleukin-6 was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and activated monocytes from blood were also enriched for IFN-γ pathway signatures in peripheral blood cells from patients with HLH compared with SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH, and comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFN-γ signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH and sepsis or SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.