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The Lancet. Child & Adolescent Health Oct 2023Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to...
BACKGROUND
Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups.
METHODS
We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex.
FINDINGS
Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup.
INTERPRETATION
Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation.
FUNDING
US National Institutes of Health and the Irving and Francine Suknow Foundation.
Topics: United States; Humans; Child; Mucocutaneous Lymph Node Syndrome; Immunoglobulins, Intravenous; Proteomics; Cluster Analysis; Aneurysm
PubMed: 37598693
DOI: 10.1016/S2352-4642(23)00166-9 -
The Clinical Respiratory Journal Jul 2023To compare the demographic and clinical features, laboratory and imaging findings in mycoplasma pneumoniae pneumonia (MPP) children with non-MPP (NMPP) children and...
BACKGROUND
To compare the demographic and clinical features, laboratory and imaging findings in mycoplasma pneumoniae pneumonia (MPP) children with non-MPP (NMPP) children and general MPP (GMPP) children with refractory MPP (RMPP) children and analysis the relationship with the severity of disease.
METHODS
The study included 265 children with MPP and 230 children with NMPP in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from 2020 to 2021. The children with MPP included RMPP (n = 85) and GMPP (n = 180). Demographic and clinical characteristics, laboratory and imaging findings of all children were measured as baseline data within 24 h after admission and the differences between MPP and NMPP, RMPP and GMPP patients were compared. ROC curves were used to evaluate the diagnostic and predictive value of different indicators for RMPP.
RESULTS
Fever duration and hospital stay in children with MPP were longer than those with NMPP. The number of patients with imaging features of pleural effusion, lung consolidation and bronchopneumonia in MPP group was significantly higher than that in NMPP group. Compared with NMPP group, the levels of C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), lactic dehydrogenase (LDH), prothrombin time (PT), fibrinogen (FIB) and D-dimer and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-10 and IL-1β) in MPP group were significantly higher (P < 0.05). The clinical symptoms and pulmonary imaging findings were more severe in RMPP group. The levels of white blood cell (WBC), CRP, PCT, SAA, ESR, alanine aminotransferase (ALT), LDH, ferritin, PT, FIB, D-dimer and inflammatory cytokines in RMPP group were higher than those in GMPP group. There was no significant difference in the level of lymphocyte subsets between the RMPP and GMPP group. IL-6, IL-10, LDH, PT, D-dimer and lung consolidation were independent risk factors for RMPP. IL-6 levels and LDH activity were good predictors of RMPP.
CONCLUSION
In conclusion, there were differences in clinical characteristics and serum inflammatory markers between MPP group and NMPP group, RMPP group and GMPP group. IL-6, IL-10, LDH, PT and D-dimer can be used as predictive indicators for RMPP.
Topics: Humans; Child; Pneumonia, Mycoplasma; Interleukin-10; Interleukin-6; Retrospective Studies; Biomarkers; Mycoplasma pneumoniae; C-Reactive Protein; Cytokines; Procalcitonin
PubMed: 37142438
DOI: 10.1111/crj.13620 -
Archivos Argentinos de Pediatria Oct 2023Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a...
Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a diagnostic delay. Here we describe 2 new cases of primary sternal osteomyelitis. Both referred fever, malaise, chest pain, and refusal to lie down, with pre-sternal erythema in one of the cases. The erythrocyte sedimentation rate and C-reactive protein values were high in both cases. The diagnosis was confirmed by imaging studies; methicillin-sensitive Staphylococcus aureus was isolated in the blood culture of one of them. Both recovered without complications with antibiotic treatment. Primary sternal osteomyelitis should be considered in the differential diagnosis of chest pain, especially if accompanied by fever, local inflammatory signs, intolerance to lying down, or increased acute phase reactants.
Topics: Child; Humans; Delayed Diagnosis; Staphylococcus aureus; Anti-Bacterial Agents; Staphylococcal Infections; Osteomyelitis; Fever; Chest Pain
PubMed: 36724129
DOI: 10.5546/aap.2022-01449.eng -
Cureus Jul 2023Osteomyelitis of the fibula is rare and is especially rare in children. The published literature is limited to case series and is thus lacking a comprehensive... (Review)
Review
Osteomyelitis of the fibula is rare and is especially rare in children. The published literature is limited to case series and is thus lacking a comprehensive description of the disease. The purpose of this systematic review is to provide the first comprehensive summary of the demographics, presenting symptoms, laboratory values, microbiology, and treatment results of osteomyelitis of the fibula in children based on the existing literature. This institutional review board (IRB)-exempt systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. Three search engines were used for a total of 239 studies. Twenty-six studies were screened by full text. Twelve articles underwent a quantitative analysis. Due to limited data and heterogenous reporting, the data were summarized descriptively. The methodologic quality of the studies was evaluated based on the Newcastle-Ottawa scale. The average age was 7.71±3.49 years, and males comprised 57% of the 21 cases. The most common presenting symptoms were fever (86%), antalgic gait (57%), and localized tenderness (81%). The most common site of involvement was the distal third of the fibula (90%). The average C-reactive protein (CRP) was 90.1±38.3 mg/L, and the average erythrocyte sedimentation rate (ESR) was 58.8±21.2 mm/hour. was the most cultured pathogen reported in 10/21 cases (48%). Open surgery was performed in 17/21 cases (81%), and there were no reported complications. Fever, antalgic gait, and localized tenderness should raise the index of suspicion. Prompt laboratory and radiographic evaluations can help reduce delays in diagnosis and improve outcomes. Blood and tissue cultures are currently performed in about half of the cases. Improvement in our microbiologic diagnosis has the potential to improve antibiotic selection. Local methicillin-resistant (MRSA) prevalence must be taken into consideration when starting empiric antibiotic treatment. Surgical treatment is often required with a low complication rate. The clinical and laboratory parameters identified in this study have the potential for integration into a composite clinical score.
PubMed: 37546085
DOI: 10.7759/cureus.41345 -
Platelets Dec 2024In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte...
In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte sedimentation (ESR), it can be expressed with the platelet antisedimentation rate (PAR), which quantitates the difference in platelet count between the upper and lower halves of the blood column after 1 h of 1 g sedimentation. Venous blood samples from 21 healthy subjects were analyzed for PAR. After a 1-h sedimentation, the upper and lower fractions of blood samples were analyzed for platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and high-fluorescence IPF (H-IPF). The mechanisms behind platelet flotation were explored by further partitioning of the blood column, time-dependent measurements of platelet count and comparison with ESR. The structure and function of the platelets were assessed by electron microscopy (EM) and atomic force microscopy (AFM), and platelet aggregometry, respectively. Platelet antisedimentation is driven by density differences and facilitated by a size-exclusion mechanism caused by progressive erythrocyte sedimentation. The area under the curve (AUC) of the whole blood adenosine diphosphate (ADP) aggregation curves showed significant differences between the upper and lower samples ( < .005). AUC in the upper samples of 38% of healthy subjects exceeded the top of the normal range (53-122) suggesting that ascending platelets show an intensified ADP-induced aggregability ex vivo. H-IPF was significantly higher in the upper samples ( < .05). EM and AFM revealed that platelets in the upper samples were larger in volume and contained 1.6 times more alpha granules compared to platelets in the lower samples. Our results indicate that antisedimentation is able to differentiate platelet populations based on their structural and functional properties. Therefore, PAR may be a suitable laboratory parameter in various thromboinflammatory disorders.
Topics: Humans; Blood Platelets; Platelet Count; Erythrocytes; Mean Platelet Volume; Adenosine Diphosphate
PubMed: 38186228
DOI: 10.1080/09537104.2023.2298341 -
Cureus Jun 2023Giant cell myocarditis (GCM) is a rare, often rapidly progressive, and potentially fatal disease because of myocardium inflammation due to the infiltration of giant... (Review)
Review
Giant cell myocarditis (GCM) is a rare, often rapidly progressive, and potentially fatal disease because of myocardium inflammation due to the infiltration of giant cells triggered by infectious as well as non-infectious etiologies. Several studies have reported that GCM can occur in patients of all ages but is more commonly found in adults. It is relatively more common among African American and Hispanic patients than in the White population. Early diagnosis and treatment are critical. Electrocardiogram (EKG), complete blood count, erythrocyte sedimentation rate, C-reactive protein, and cardiac biomarkers such as troponin and brain natriuretic peptide (BNP), echocardiogram, cardiac magnetic resonance imaging (MRI), myocardial biopsy, and myocardial gene profiling are useful diagnostic tools. Current research has identified several potential biomarkers for GCM, including myocarditis-associated immune cells, cytokines, and other chemicals. The standard of care for GCM includes aggressive immunosuppressive therapy with corticosteroids and immunomodulatory agents like rituximab, cyclosporine, and infliximab, which have shown promising results in GCM by balancing the immune system and preventing the attack on healthy tissues, resulting in the reduction of inflammation, promotion of healing, and decreasing the necessity for cardiac transplantation. Without immunosuppression, the chance of mortality or cardiac surgery was 100%. Multiple studies have revealed that a treatment combination of corticosteroids and immunomodulatory agents is superior to corticosteroids alone. Combination therapy significantly increased transplant-free survival (TFS) and decreased the likelihood of heart transplantation, hence improving overall survival. It is important to balance the benefits of immunosuppression with its potentially adverse effects. In conclusion, immunomodulatory therapy adds significant long-term survival benefits to GCM.
PubMed: 37456487
DOI: 10.7759/cureus.40439 -
BMC Rheumatology Oct 2023The inflammasome plays an important role in rheumatoid arthritis (RA), which has rarely been systematically reported. The aim of this study was to understand whether the...
BACKGROUND
The inflammasome plays an important role in rheumatoid arthritis (RA), which has rarely been systematically reported. The aim of this study was to understand whether the levels of inflammasomes were related to the severity of RA disease, which might provide a stronger theoretical basis for RA treatment.
METHODS
The mRNA expression levels of some inflammasomes and associated molecules, including IL-1beta and IL-18, in peripheral blood mononuclear cells (PBMCs) from 30 RA patients (n = 30) and 16 healthy control (HC) individuals were determined by quantitative real-time polymerase chain reaction (qRT‒PCR), and the levels of plasma IL-1beta and IL-18 were also measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the clinical characteristics and laboratory results of the patients were collected and analyzed in this study.
RESULTS
The relative mRNA expression levels of NLRP3, NLRC4, AIM2, caspase-1, and IL-1beta were significantly higher and those of NLRP1, NLRP2 and NLRC5 were notably lower in the HC group than in the RA group. Moreover, the plasma IL-1beta and IL-18 levels were markedly increased in the RA group. Additionally, the mRNA level of AIM2 was negatively correlated with disease activity score 28 (DAS28) by stepwise linear regression analysis. erythrocyte sedimentation rate (ESR) was positively correlated with DAS28 by multiple linear regression analysis in the RA group.
CONCLUSIONS
These findings imply the critical role of NLRP3, NLRC4, AIM2, caspase-1 and plasma IL-1beta and IL-18 in the pathogenesis of RA patients, which provides potential targets for the treatment of RA.
PubMed: 37899476
DOI: 10.1186/s41927-023-00353-8 -
Therapeutics and Clinical Risk... 2023For the diagnosis of pediatric osteomyelitis, the sensitivity, specificity, and predictive value of erythrocyte sedimentation rate (ESR) were evaluated in this study. (Review)
Review
OBJECTIVE
For the diagnosis of pediatric osteomyelitis, the sensitivity, specificity, and predictive value of erythrocyte sedimentation rate (ESR) were evaluated in this study.
METHODS
A systematic computer-based search was performed for relevant articles focusing on the ESR diagnosis of pediatric osteomyelitis in PubMed, Embase, and the Cochrane Library with an inclusion criteria: 1) the diagnostic utility of ESR for diagnosing osteomyelitis patients under the age of 18;2) two-by-two contingency tables can be obtained. Case reports, review papers, and animal experiments were excluded.
RESULTS
The diagnostic meta-analysis included 8 studies involving 348 children with osteomyelitis, all of whom were tested for ESR. Diagnostic meta-analysis revealed a sensitivity and specificity of 0.90, 95% confidence interval (CI) (0.86-0.93), and 0.50 (95% CI,0.47-0.54) for ESR in pediatric osteomyelitis diagnosis, respectively. The positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 1.38,(95% CI,1.08-1.78), 0.46, (95% CI,0.26-0.73), and 3.20, (95% CI,1.33-7.69), respectively. The area under the curve (AUC) was determined to be 0.80 based on the summary receiver operating characteristic curve (SROC).
CONCLUSION
The literature on the use of ESR in pediatric osteomyelitis diagnosis was thoroughly reviewed in this study. It was also found that ESR may be useful as a biomarker for pediatric osteomyelitis diagnosis. Due to its low specificity, it should be used in combination with other markers such as C-reactive protein, neutrophil percentage, and white blood cell count.
PubMed: 38089965
DOI: 10.2147/TCRM.S440996