ABSTRACT
BACKGROUND: Fetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients' hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts. CASE PRESENTATION: We performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies' alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16month and14- month followup period, their motor and intellectual development was normal. CONCLUSIONS: . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.
Subject(s)
Leukemoid Reaction , Systemic Inflammatory Response Syndrome , Humans , Leukemoid Reaction/diagnosis , Leukemoid Reaction/blood , Leukemoid Reaction/etiology , Female , Infant, Newborn , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/blood , Pregnancy , Infant, Premature , Male , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/bloodABSTRACT
BACKGROUND: Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. METHODS AND RESULTS: Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. CONCLUSIONS: We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. REGISTRATION: https://www.clinicaltrials.gov Unique identifier: NCT01662895.
Subject(s)
Anemia , Biomarkers , Cerebral Hemorrhage , Hemoglobins , Inflammation , Humans , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/epidemiology , Male , Female , Anemia/blood , Anemia/diagnosis , Anemia/epidemiology , Aged , Middle Aged , Biomarkers/blood , Hemoglobins/metabolism , Hemoglobins/analysis , Inflammation/blood , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Deferoxamine/therapeutic use , Time Factors , Treatment Outcome , Iron/blood , PrevalenceABSTRACT
This study aimed to assess the significance of serum albumin levels within 24 h of patient admission in correlation with the incidence of outcomes and mortality in patients diagnosed with acute pancreatitis. A retrospective study was conducted over a 5-year period, from January 2018 to December 2023, at the Mohammed VI University Hospital in Oujda, Morocco. The study included 371 patients diagnosed with acute pancreatitis. Hypoalbuminemia (≤ 30 g/L) was observed in 124 patients (33.4% of cases), and these patients had a higher mean age compared to those with normal albumin levels (P = 0.003). Hypoalbuminemia was significantly associated with persistent Systemic Inflammatory Response Syndrome (SIRS) (70.8% vs. 29.2%, P = 0.000), a higher BISAP score (66.7% vs. 33.3%, P = 0.000), and a higher CTSI score (51.7% vs. 48.3%, P = 0.000). Hypoalbuminemia was also associated with the presence of pleural effusion (P = 0.000). The mortality in the sample was 4.6%, and it was significantly associated with hypoalbuminemia (76.5%, P = 0.000). In conclusion, serum albumin levels within 24 h of patient admission appear to be a significant prognostic biomarker in acute pancreatitis, particularly in anticipating persistent organ failure and mortality.
Subject(s)
Biomarkers , Hypoalbuminemia , Pancreatitis , Serum Albumin , Systemic Inflammatory Response Syndrome , Humans , Male , Female , Retrospective Studies , Pancreatitis/blood , Pancreatitis/mortality , Pancreatitis/diagnosis , Biomarkers/blood , Middle Aged , Hypoalbuminemia/blood , Serum Albumin/analysis , Prognosis , Adult , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Aged , Acute Disease , Severity of Illness Index , Morocco/epidemiologyABSTRACT
BACKGROUND: Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). METHODS: Patients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1ß, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. RESULTS: Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2-4.5 vs. CECC 4.6 pg/mL; CI 3.4-5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. CONCLUSIONS: Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. CLINICAL REGISTRATION NUMBER: NCT03216720.
Subject(s)
Coronary Artery Bypass , Extracorporeal Circulation , Systemic Inflammatory Response Syndrome , Humans , Male , Female , Extracorporeal Circulation/methods , Middle Aged , Aged , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiology , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Biomarkers/blood , Tumor Necrosis Factor-alpha/blood , Postoperative Complications/bloodABSTRACT
The role of programmed death cell protein 1 (PD-1) has already been described in a range of various diseases, including COVID-19. This study provides new, innovative data, related to the expression of PD-1 and the risk of Paediatric Inflammatory Multisystem Syndrome, temporally associated with SARS-CoV-2 infection (PIMS-TS)-a rare, but potentially life-threatening complication of COVID-19. In this study, we evaluated the expression of PD-1 protein in patients with PIMS. Blood samples were taken from patients at the time of diagnosis (n = 33), after 6 weeks (n = 33), 3 months (n = 24), 6 months (n = 24) and 12 months (n = 8). The immunophenotypes were evaluated in flow cytometry. The control group consisted of 35 healthy children with negative SARS-CoV-2 antigen/PCR test, who were asymptomatic and had no history of allergic, autoimmune or oncological diseases. The associations between immunophenotypes, biochemical findings and clinical data were analysed. Significant increases in the expression of PD-1 for CD4+ and CD8+ T cells, compared to the control group, were observed in the day of admission, with a gradual decrease during the first weeks from initiation of treatment. This study sheds new light on the pathogenesis of PIMS-TS, emphasizing the role of PD-1 protein. Future research is essential for early risk prediction in SARS-CoV-2 patients and for devising effective clinical prevention and management strategies.
Subject(s)
COVID-19 , Programmed Cell Death 1 Receptor , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Humans , COVID-19/complications , COVID-19/immunology , COVID-19/blood , COVID-19/metabolism , Programmed Cell Death 1 Receptor/metabolism , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Male , Child , Female , Child, Preschool , Prospective Studies , Adolescent , Infant , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , ImmunophenotypingABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis.
Subject(s)
COVID-19 , Proteomics , Systemic Inflammatory Response Syndrome , Humans , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/blood , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/complications , Child , Proteomics/methods , Female , Male , Child, Preschool , SARS-CoV-2 , Adolescent , Biomarkers/blood , Artificial Intelligence , InfantABSTRACT
Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.
Subject(s)
Autoantibodies , COVID-19 , Cytokines , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Humans , COVID-19/immunology , COVID-19/blood , COVID-19/complications , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/blood , Child , Female , Male , Prospective Studies , SARS-CoV-2/immunology , Child, Preschool , Autoantibodies/blood , Autoantibodies/immunology , Cytokines/blood , Adolescent , Infant , Biomarkers/blood , Antibodies, Viral/blood , Inflammation/immunology , Inflammation/bloodSubject(s)
COVID-19 , Critical Illness , Fibrin Fibrinogen Degradation Products , Systemic Inflammatory Response Syndrome , Humans , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/blood , Fibrin Fibrinogen Degradation Products/analysis , Child , COVID-19/diagnosis , COVID-19/blood , COVID-19/complications , Biomarkers/blood , Child, PreschoolABSTRACT
BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.
Subject(s)
Anastomotic Leak , Biomarkers , C-Reactive Protein , Esophagectomy , Humans , Anastomotic Leak/blood , Anastomotic Leak/diagnosis , Anastomotic Leak/etiology , Biomarkers/blood , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Esophageal Neoplasms/surgery , Esophageal Neoplasms/blood , Esophagectomy/adverse effects , Leukocyte Count , Predictive Value of Tests , Serum Albumin/analysis , Serum Albumin/metabolism , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/diagnosisABSTRACT
Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1ß, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.
Subject(s)
Acute Febrile Encephalopathy , Biomarkers , COVID-19 , Scrub Typhus , Systemic Inflammatory Response Syndrome , Humans , India/epidemiology , Child , Male , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Female , COVID-19/complications , COVID-19/blood , COVID-19/diagnosis , Child, Preschool , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/blood , Scrub Typhus/diagnosis , Scrub Typhus/complications , Scrub Typhus/blood , Scrub Typhus/cerebrospinal fluid , Acute Febrile Encephalopathy/blood , Acute Febrile Encephalopathy/etiology , Acute Febrile Encephalopathy/diagnosis , Adolescent , Infant , Cytokines/blood , Cytokines/cerebrospinal fluidABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) shares several clinical and immunological features with Kawasaki Disease (KD) and pediatric hyperinflammation, but the immuno-phenotypic overlap among these clinical mimics is still incompletely understood. Here we analyzed serum samples from treatment-naïve patients with MIS-C (n = 31) and KD (n = 11), pediatric hyperinflammation (n = 13) and healthy controls (HC, n = 10) by proximity extension assay (PEA) to profile 184 blood biomarkers. Collectively, immunophenotypic overlap between MIS-C and hyperinflammation exceeds overlap with KD. Overexpression of IL-17A in MIS-C and KD could best separate these conditions from hyperinflammatory conditions, while those were hallmarked by overabundance of adenosin deaminase and IL-18. Depletion in serum TNF-related subfamily member 9 (TNFRSF9) and apoptosis inducing ligand (TRAIL) linked with cardiovascular manifestations and myocarditis in MIS-C. Altogether, our analysis highlights important differences in molecular marker signatures also across different MIS-C and KD cohorts and suggests several previously unidentified molecular associations in context of cardiovascular inflammation.
Subject(s)
Biomarkers , Mucocutaneous Lymph Node Syndrome , Proteomics , Systemic Inflammatory Response Syndrome , Humans , Biomarkers/blood , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/immunology , Male , Female , Proteomics/methods , Child , Child, Preschool , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/immunology , Inflammation/blood , Infant , Interleukin-17/blood , TNF-Related Apoptosis-Inducing Ligand/blood , Interleukin-18/blood , Adenosine Deaminase/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/immunologyABSTRACT
OBJECTIVE: We investigated the effect of Remote Ischemic Preconditioning (RIPC) on the inflammatory response during CPB by means of serum presepsin levels at preoperative and postoperative 1st and 24th h. METHODS: In this prospective, randomized, cross-sectional study we included 81 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). Patients were randomized and RIPC was applied to 40 patients in the study group before anesthesia. The remaining 41 patients were determined as the control group. The relationships between RIPC and factors such as presepsin, C-reactive protein (CRP), and leukocyte levels were investigated. RESULTS: There was no significant difference between the groups in postoperative leukocyte and CRP values (p = 0.52, p = 0.13, respectively). When the preoperative and postoperative first hour presepsin values of the patients were compared, no significant difference was found in the control group (p = 0.17), but a significant difference was found in the study group (p < 0.05). When the presepsin values were compared between the groups, a significant difference was found only in the postoperative first hour value (p < 0.05). CONCLUSIONS: It was observed that RIPC application caused to increase the presepsin levels in the postoperative first hour significantly in the study group (p < 0.05).
Subject(s)
Biomarkers , C-Reactive Protein , Coronary Artery Bypass , Lipopolysaccharide Receptors , Peptide Fragments , Humans , Lipopolysaccharide Receptors/blood , Male , Female , Peptide Fragments/blood , Prospective Studies , Middle Aged , Aged , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Coronary Artery Bypass/adverse effects , Cross-Sectional Studies , Biomarkers/blood , Ischemic Preconditioning/methods , Cardiopulmonary Bypass/adverse effects , Time Factors , Leukocyte Count , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/prevention & control , Systemic Inflammatory Response Syndrome/etiology , Treatment OutcomeABSTRACT
Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Systemic Inflammatory Response Syndrome , Thrombocytopenia , Humans , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/genetics , Child , Male , Child, Preschool , Female , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/immunology , Thrombocytopenia/blood , Thrombocytopenia/immunology , Infant , Adolescent , Phenotype , Proteomics , COVID-19/immunology , COVID-19/blood , COVID-19/complicationsABSTRACT
Background and Objectives: Systemic inflammatory response syndrome (SIRS) is one of the most significant complications after on-pump heart surgery procedures. High cytokine levels have been shown after open-heart surgeries and a genetic predisposition seems to be an important underlying modulatory characteristic for SIRS. To investigate the association between interleukin 18 -607 C/A, interleukin 18 -137 G/C and osteopontin 9250 C/T genetic polymorphisms and SIRS in on-pump CABG patients. Materials and Methods: Two hundred consecutive elective on-pump CABG patients were recruited prospectively to the study. Genomic DNA was extracted from whole blood and genotyping was determined by sequence specific PCR or PCR-RFLP methods for related polymorphisms. Results: SIRS incidence was 60.2%, 38.1%, 18.9% on postoperative day 1, 2 and 3, respectively, in the whole study population. The SIRS rate on the second postoperative day was 13% and 43.4%, respectively, in osteopontin 9250 C/T T allele non-carriers and carriers (p = 0.004). WBC (White Blood Cell) counts were higher on day 2 and 3 in osteopontin 9250 C/T T allele carriers compared to non-carriers (day 2; 12.7 ± 4 vs. 10.5 ± 2.4 (p = 0.015), day 3; 11.8 ± 4 vs. 9.1 ± 4.7 (p = 0.035)). The average ICU stay was 3.1 ± 7.4, 1.28 ± 0.97 for IL 18-137 G/C C allele carriers and non-carriers, respectively (p = 0.003), and in the IL 18-137 G/C C allele carriers, SIRS developed in 42.2% by the second postoperative day whereas the rate was 57.8% in non-carriers (p = 0.025). Conclusions: The current research revealed a possible link between osteopontin 9250 C/T and IL18-137 G/C genetic polymorphism and SIRS and morbidity in on-pump CABG patients.
Subject(s)
Coronary Artery Bypass , Interleukin-18 , Osteopontin , Systemic Inflammatory Response Syndrome , Aged , Female , Humans , Male , Middle Aged , Coronary Artery Bypass/adverse effects , Genetic Predisposition to Disease , Genotype , Interleukin-18/blood , Interleukin-18/genetics , Interleukin-18/immunology , Osteopontin/blood , Osteopontin/genetics , Osteopontin/immunology , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Prospective Studies , Systemic Inflammatory Response Syndrome/genetics , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiologyABSTRACT
To utilize metabolomics in conjunction with RNA sequencing to identify biomarkers in the blood of sepsis patients and discover novel targets for diagnosing and treating sepsis. In January 2019 and December 2020, blood samples were collected from a cohort of 16 patients diagnosed with sepsis and 11 patients diagnosed with systemic inflammatory response syndrome (SIRS). Non-targeted metabolomics analysis was conducted using liquid chromatography coupled with mass spectrometry (LC-MS/MS technology), while gene sequencing was performed using RNA sequencing. Afterward, the metabolite data and sequencing data underwent quality control and difference analysis, with a fold change (FC) greater than or equal to 2 and a false discovery rate (FDR) less than 0.05.Co-analysis was then performed to identify differential factors with consistent expression trends based on the metabolic pathway context; KEGG enrichment analysis was performed on the crossover factors, and Meta-analysis of the targets was performed at the transcriptome level using the public dataset. In the end, a total of five samples of single nucleated cells from peripheral blood (two normal controls, one with systemic inflammatory response syndrome, and two with sepsis) were collected and examined to determine the cellular location of the essential genes using 10× single cell RNA sequencing (scRNA-seq). A total of 485 genes and 1083 metabolites were found to be differentially expressed in the sepsis group compared to the SIRS group. Among these, 40 genes were found to be differentially expressed in both the metabolome and transcriptome. Functional enrichment analysis revealed that these genes were primarily involved in biological processes related to inflammatory response, immune regulation, and amino acid metabolism. Furthermore, a meta-analysis identified four genes, namely ITGAM, CD44, C3AR1, and IL2RG, which were highly expressed in the sepsis group compared to the normal group (P < 0.05). Additionally, scRNA-seq analysis revealed that the core genes ITGAM and C3AR1 were predominantly localized within the macrophage lineage. The primary genes ITGAM and C3AR1 exhibit predominant expression in macrophages, which play a significant role in inflammatory and immune responses. Moreover, these genes show elevated expression levels in the plasma of individuals with sepsis, indicating their potential as valuable subjects for further research in sepsis.
Subject(s)
Biomarkers , Metabolomics , Sepsis , Humans , Sepsis/genetics , Sepsis/blood , Sepsis/metabolism , Biomarkers/blood , Metabolomics/methods , Male , Female , Middle Aged , Transcriptome , Gene Expression Profiling , Aged , Adult , Chromatography, Liquid , Tandem Mass Spectrometry , Systemic Inflammatory Response Syndrome/genetics , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/diagnosisABSTRACT
BACKGROUND: PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. OBJECTIVE: To identify factors associated with increased PIMS-TS severity in children. METHODS: In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. RESULTS: A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. CONCLUSION: The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.
Subject(s)
Biomarkers , COVID-19 , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome , Humans , COVID-19/blood , COVID-19/epidemiology , COVID-19/diagnosis , COVID-19/complications , Switzerland/epidemiology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Child , Prospective Studies , Male , Female , Child, Preschool , Biomarkers/blood , Infant , Adolescent , Risk FactorsABSTRACT
Coronavirus disease 2019 (COVID-19) is frequently associated with thrombo inflammation, which can predispose to developing of life-threatening conditions in children such as the multisystem inflammatory syndrome (MIS-C) and Kawasaki disease. Because of the consistent overlap in pathogenesis and symptoms, identifying laboratory tests that may aid in the differential diagnosis of these pathologies becomes crucial. We performed an electronic search in PubMed, Web of Science and Scopus, without date or language restrictions, to identify all possible studies reporting D-dimer values in separate cohorts of children with MIS-C or Kawasaki disease. Three multicenter cohort studies were included in our analysis, totaling 487 patients (270 with MIS-C and 217 with Kawasaki disease). In this meta-analysis, significantly higher D-dimer values were found in MIS-C compared to Kawasaki disease in all three studies, yielding an SMD of 1.5 (95â¯% CI, 1.3-1.7) mg/L. Thus, very high D-dimer values early in the course of disease should raise the clinical suspicion of MIS-C rather than Kawasaki disease. Further studies should be planned to identify harmonized D-dimer diagnostic thresholds that may help discriminate these conditions.
Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products , Mucocutaneous Lymph Node Syndrome , Systemic Inflammatory Response Syndrome , Humans , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/blood , Diagnosis, Differential , COVID-19/diagnosis , COVID-19/blood , COVID-19/complications , Child , Biomarkers/blood , Child, Preschool , SARS-CoV-2/isolation & purificationABSTRACT
OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.
Subject(s)
Cytokines , Mucocutaneous Lymph Node Syndrome , Shock, Septic , Systemic Inflammatory Response Syndrome , Yersinia pseudotuberculosis Infections , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/diagnosis , Cytokines/blood , Humans , Interleukin-6/blood , Chemokine CXCL9/blood , Macrophage Activation Syndrome/blood , Macrophage Activation Syndrome/diagnosis , Male , Female , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Diagnosis, Differential , Shock, Septic/blood , Shock, Septic/diagnosis , Yersinia pseudotuberculosis Infections/blood , Yersinia pseudotuberculosis Infections/diagnosis , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosisABSTRACT
OBJECTIVE: Patients with ureteral calculi and systemic inflammatory response syndrome (SIRS) often require emergency drainage, and percutaneous nephrostomy (PCN) and retrograde ureteral stent insertion (RUSI) are the most commonly used methods. Our study aimed to identify the best choice (PCN or RUSI) for these patients and to examine the risk factors for progression to urosepsis after decompression. METHODS: A prospective, randomized clinical study was performed at our hospital from March 2017 to March 2022. Patients with ureteral stones and SIRS were enrolled and randomized to the PCN or RUSI group. Demographic information, clinical features and examination results were collected. RESULTS: Patients (n = 150) with ureteral stones and SIRS were enrolled into our study, with 78 (52%) patients in the PCN group and 72 (48%) patients in the RUSI group. Demographic information was not significantly different between the groups. The final treatment of calculi was significantly different between the two groups (p < .001). After emergency decompression, urosepsis developed in 28 patients. Patients with urosepsis had a higher procalcitonin (p = .012) and blood culture positivity rate (p < .001) and more pyogenic fluids during primary drainage (p < .001) than patients without urosepsis. CONCLUSION: PCN and RUSI were effective methods of emergency decompression in patients with ureteral stone and SIRS. Patients with pyonephrosis and a higher PCT should be carefully treated to prevent the progression to urosepsis after decompression.Key messageIn this study, we evaluate the best choice (PCN or RUSI) for patients who have ureteral stones and SIRS and to examine the risk factors for progression to urosepsis after decompression. This study found that PCN and RUSI were effective methods of emergency decompression. Pyonephrosis and higher PCT were risk factors for patients to develop to urosepsis after decompression.