Changes in Levels of Serum Cytokines and Chemokines in Perforated Appendicitis in Children.

Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.

The Role of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Predicting Complicated Appendicitis in Children.

BACKGROUND: Acute appendicitis is a common abdominal emergency observed in emergency departments (ED). Distinguishing between uncomplicated and complicated appendicitis is important in determining a treatment strategy. Serum soluble vascular cell adhesion molecule-1 (VCAM-1) is an inflammatory biomarker. We aimed to determine the role of VCAM-1 in predicting complicated appendicitis in children. METHODS: Pediatric patients with suspected appendicitis admitted to the ED were enrolled in this prospective study. Pre-surgical serum VCAM-1 was tested in children with acute appendicitis within 72 h of symptoms (from day 1 to day 3). Serum VCAM-1 levels were further analyzed and compared between patients with and without complicated appendicitis. RESULTS: Among the 226 pediatric appendicitis patients, 70 had uncomplicated appendicitis, 138 had complicated appendicitis, and 18 had normal appendices. The mean serum VCAM-1 levels in patients with perforated appendicitis were higher than in those with simple appendicitis (p < 0.001). On day 1 to day 3, the mean VCAM-1 levels in patients with complicated appendicitis were all significantly higher than in those with uncomplicated appendicitis (all p < 0.001). CONCLUSION: Serum VCAM-1 levels may be helpful in differentiating uncomplicated and complicated appendicitis in children and could predict appendiceal perforation.

Treatment of Undifferentiated Embryonal Sarcoma of the Liver in Children.

Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal tumor with a highly malignant potential. It occurs almost exclusively in the pediatric population and typically has a poor outcome. Although previous studies have reported dismal prognoses, recent advances in combined treatment modalities, e.g., surgery and chemotherapy, have given cause for optimism. Even in those diseases not amenable to complete surgical resection or refractory diseases, other treatment modalities, such as liver transplant, have yielded promising results. This paper provides a review of the current treatment modalities for hepatic undifferentiated embryonal sarcoma in children.

Presentations of Children with Suspected Sepsis Caused by Acute Infectious Diarrhea in the Pediatric Emergency Department.

BACKGROUND: Acute infectious diarrhea is a common cause of hospitalization in children. Hence, early identification of acute bacterial gastroenteritis with suspected sepsis in pediatric emergency departments (EDs) is important. This study aimed to describe the clinical spectrum and initial characteristics of children who were presented to a pediatric ED with acute infectious diarrhea and suspected sepsis. METHODS: Between April 2020 to March 2021, children with clinical diagnoses of acute bacterial colitis and suspected sepsis who were admitted to the pediatric ED were prospectively enrolled. The following data were obtained and compared between different age groups of children: including demographics, presentation, laboratory tests, culture results, treatment modalities, complications, and short-term outcomes. RESULTS: A total of 105 patients (70 males and 35 females; mean age: 3.75 ± 3.52 years) were enrolled in this study. Of them, 89 (84.8%) patients were <6 years of age, and 80 (76.2%) patients required hospitalization for a duration of 4.7 ± 2.08 days. C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher in the admission (both p < 0.001) and anti-biotic treatment groups (both p < 0.001). Salmonella enteritidis was the most common organism cultured from the stool and blood samples (39 of 91 (38.5%) and 2 of 105 (1.9%), respectively). CONCLUSIONS: The primary causative organism of acute infectious diarrhea identified in this study was S. enteritidis. Age and elevated serum CRP or PCT levels could be important factors in the decisions of emergency physicians regarding hospitalization and antibiotic therapies for pediatric acute infectious diarrhea.

Risk Factors for Urinary Tract Infections in Children with Hematuria in the Emergency Department.

INTRODUCTION: Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that can predict UTIs in hematuria patients without pyuria in the pediatric emergency department (ED). METHODS: We retrospectively recruited patients with hematuria from the pediatric ED. Clinical symptoms, urine biochemistry and microscopic examination results, and blood laboratory tests were analyzed to identify the predictors of UTIs. Patients were divided into the verbal group (age ≥ 2 years) and non-verbal group (age < 2 years) for identifying predictors of UTIs. Causes of hematuria were also investigated. RESULTS: A total of 161 patients with hematuria without pyuria were evaluated. Among symptoms, dysuria was significantly correlated with UTIs. Regarding urine biochemistry data, urine esterase and urine protein > 30 mg/dl were found to be significant parameters for predicting UTIs, while urine esterase and urine nitrite showed significant differences in children with age < 2 years. In the urine microscopic examinations, urine red blood cells (RBC) > 373/µL in children aged ≥ 2 years and urine RBC > 8/µL in children aged < 2 years were associated with UTIs. In addition, UTIs and urinary tract stones were found to be the top two causes of hematuria. CONCLUSIONS: Dysuria, urine esterase, urine nitrite, and urine protein may be useful parameters for predicting UTIs in pediatric patients with hematuria but no pyuria in the ED. In addition, a UTI was the most commonly identified etiology of hematuria without pyuria, followed by urinary tract stones.

Advancements in Allergen Immunotherapy for the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects individuals of all age groups, manifesting as a spectrum of symptoms varying from mild to severe. Allergen immunotherapy (AIT) involves the administration of allergen extracts and has emerged as a potential treatment strategy for modifying immune responses. Its pathogenesis involves epidermal barrier dysfunction, microbiome imbalance, immune dysregulation, and environmental factors. Existing treatment strategies encompass topical steroids to systemic agents, while AIT is under investigation as a potential immune-modifying alternative. Several studies have shown reductions in the severity scoring of atopic dermatitis (SCORAD) scores, daily rescue medication use, and visual analog scale (VAS) scores following AIT. Biomarker changes include increased IgG4 levels and decreased eosinophil counts. This review provides valuable insights for future research and clinical practice, exploring AIT as a viable option for the management of AD.

Stem Cell Therapy in Children with Traumatic Brain Injury.

Pediatric traumatic brain injury is a cause of major mortality, and resultant neurological sequelae areassociated with long-term morbidity. Increasing studies have revealed stem cell therapy to be a potential new treatment. However, much work is still required to clarify the mechanism of action of effective stem cell therapy, type of stem cell therapy, optimal timing of therapy initiation, combination of cocurrent medical treatment and patient selection criteria. This paper will focus on stem cell therapy in children with traumatic brain injury.

Mesenchymal Stem Cells in the Treatment of COVID-19.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.

Predictors of bacteremia in febrile infants under 3 months old in the pediatric emergency department.

INTRODUCTION: Fever may serve as the primary indicator of underlying infection in children admitted to the pediatric emergency department (PED), especially in high-risk young infants. This study aimed to identify early clinical factors that could help predict bacteremia in young febrile infants. METHODS: The study included infants under 90 days of age who were admitted to the PED due to fever. Patients were divided into two groups based on the presence or absence of bacteremia and further divided into three age groups: (1) less than 30 days, (2) 30 to 59 days, and (3) 60 to 90 days. Several clinical and laboratory variables were analyzed, and logistic regression and receiver operating characteristic (ROC) analyses were used to identify potential risk factors associated with bacteremia in young febrile infants. RESULTS: A total of 498 febrile infants were included, of whom 6.4% were diagnosed with bacteremia. The bacteremia group had a higher body temperature (BT) at triage, especially in neonates, higher pulse rates at triage, longer fever subsidence time, longer hospital stays, higher neutrophil counts, and higher C-reactive protein (CRP) levels than those of the non-bacteremia group. ROC analysis showed that the best cut-off values for predicting bacteremia in infants with pyrexia were a BT of 38.7 °C, neutrophil count of 57.9%, and CRP concentration of 53.8 mg/L. CONCLUSIONS: A higher BT at triage, increased total neutrophil count, and elevated CRP levels may be useful for identifying bacteremia in young febrile infants admitted to the PED.

Personalized Medicine in Severe Asthma: From Biomarkers to Biologics.

Severe asthma is a complex and heterogeneous clinical condition presented as chronic inflammation of the airways. Conventional treatments are mainly focused on symptom control; however, there has been a shift towards personalized medicine. Identification of different phenotypes driven by complex pathobiological mechanisms (endotypes), especially those driven by type-2 (T2) inflammation, has led to improved treatment outcomes. Combining biomarkers with T2-targeting monoclonal antibodies is crucial for developing personalized treatment strategies. Several biological agents, including anti-immunoglobulin E, anti-interleukin-5, and anti-thymic stromal lymphopoietin/interleukin-4, have been approved for the treatment of severe asthma. These biological therapies have demonstrated efficacy in reducing asthma exacerbations, lowering eosinophil count, improving lung function, diminishing oral corticosteroid use, and improving the quality of life in selected patients. Severe asthma management is undergoing a profound transformation with the introduction of ongoing and future biological therapies. The availability of novel treatment options has facilitated the adoption of phenotype/endotype-specific approaches and disappearance of generic interventions. The transition towards precision medicine plays a crucial role in meticulously addressing the individual traits of asthma pathobiology. An era of tailored strategies has emerged, allowing for the successful targeting of immune-inflammatory responses that underlie uncontrolled T2-high asthma. These personalized approaches hold great promise for improving the overall efficacy and outcomes in the management of severe asthma. This article comprehensively reviews currently available biological agents and biomarkers for treating severe asthma. With the expanding repertoire of therapeutic options, it is becoming increasingly crucial to comprehend the influencing factors, understand the pathogenesis, and track treatment progress in severe asthma.

Systemic lupus erythematosus and thyroid disease - Experience in a single medical center in Taiwan.

BACKGROUND: To investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan. METHODS: This is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia. RESULTS: Compared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001). CONCLUSION: SLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement.

Comparison of Total Joint Replacement Rate Between Patients With Hemophilia A and Patients With Hemophilia B: A Population-Based and Retrospective Cohort Study.

Recurrent hemarthrosis in patients with hemophilia (PWH) results in chronic arthropathy requiring total joint replacement (TJR). This study aimed to compare the difference in TJR rate between patients with hemophilia A (HA) and hemophilia B (HB). A final total of 935 PWH (782 HA and 153 HB) without inhibitors were collected from the Taiwan's National Health Insurance Research Database between 1997 and 2013. Demographics, clinical characteristics, and TJR rate were compared between the 2 groups. The annual use of clotting factor concentrate was not different between HA and HB groups (P = .116). The rate of comorbidities except for 29 PWH having HIV who were all in the HA group was also not different between the 2 groups. A total of 99 (10.6%) PWH had undergone 142 TJR procedures during the study period. All of them had received on-demand therapy. No difference was found in the cumulative incidence of TJR between HA and HB (P = .787). After adjusting for various confounders including age, pyogenic arthritis, and HIV infection, no increased risk of TJR was found in patients with HA versus Patients with HB (hazard ratio: 0.92, 95% confidence interval 0.54-1.58). This finding suggests that the rate of TJR between patients with HA and HB is not significantly different.

Systemic lupus erythematosus and thyroid disease: A 10-year study.

BACKGROUND: This large-scale study aims to analyze the association of systemic lupus erythematosus (SLE) with thyroid diseases. METHODS: In this retrospective, nationwide cohort study, 1633 newly diagnosed SLE patients from the National Health Insurance Research Database in 2000 were examined and data on patients with diagnoses of hyperthyroidism, hypothyroidism, and autoimmune thyroiditis were collected from 2000 to 2009. We subdivided these SLE patients by the presence of overlap syndrome. Comparison with 6532 age- and sex-matched controls was performed. RESULTS: The cumulative incidence of thyroid disease in SLE patients was lower than in controls (8.1% vs. 16.9%, p < 0.001). Among SLE patients, 39.7% had overlap syndrome. The overlap syndrome group had a higher cumulative incidence of thyroid diseases (10.96% vs. 4.57%, p < 0.0001), hypothyroidism (3.86% vs. 1.93%, p = 0.017), and autoimmune thyroiditis (4.63% vs. 0.71%, p < 0.0001) than SLE patients without overlap syndrome. Comparing the data with the non-SLE-matched control group by logistic regression model revealed a decreased risk of thyroid diseases with odds ratios (ORs) of 0.25 and 0.62 [95% confidence interval (CI) 0.18-0.33, 0.48-0.80], and hyperthyroidism with ORs of 0.21 and 0.30 (95% CI 0.14-0.31, 0.20-0.45) in SLE patients without and with overlap syndrome. SLE patients without overlap syndrome had a lower risk of hypothyroidism with an OR of 0.53 (95% CI 0.53-0.86) and autoimmune thyroiditis with an OR of 0.26 (95% CI 0.12-0.56). SLE patients with overlap syndrome showed a similar risk of hypothyroidism with an OR of 0.92 (95% CI 0.66-1.53) and a higher risk of autoimmune thyroiditis with OR of 1.69 (95% CI 1.14-2.51). CONCLUSION: SLE patients had a significantly lower rate of thyroid diseases and hyperthyroidism than matched controls. Among SLE patients, risks of hypothyroidism and autoimmune thyroiditis were different in the presence of overlap syndrome. This finding is novel and important for clinical practices.

Risk of subsequent asthma in children with febrile seizures: a nationwide population-based retrospective cohort study.

BACKGROUND: No study has reported a relationship between febrile seizures and asthma; thus, we examined the association between these two disorders. METHODS: We identified 991 cases of children with febrile seizures as the case cohort, and the control group was matched according to age, sex, urbanization level, and their parents' occupation at a 1:4 ratio. We applied the Cox proportional hazards regression model to estimate the hazard ratios and 95% confidence intervals for asthma among the children with febrile seizures. RESULTS: After 11 years of follow-up, the asthma incidence in the febrile seizure group was approximately 5% higher than that in the control group (log-rank test, P < 0.0001). The risk of asthma in the febrile seizure group was 1.41 times higher than that in the control group (95% confidence interval, 1.21-1.65; P < 0.001). Furthermore, the risk of asthma development increased (0.96 vs 3.62) in conjunction with the frequency of febrile seizure-related medical visits (one to two visits vs more than four visits; P < 0.0001). CONCLUSION: Febrile seizures may be associated with an increase in the risk of future asthma occurrence in children. We observed a significantly higher cumulative incidence of asthma occurrence in children with more febrile seizure-related medical visits.

Increased association between febrile convulsion and allergic rhinitis in children: a nationwide population-based retrospective cohort study.

BACKGROUND AND OBJECTIVES: Febrile convulsions and allergic rhinitis are both common childhood disorders and both are considered as generally benign disorders. Yet, especially in the case of allergic rhinitis, adverse effects on school performance and limited socialization are found. The relationship between febrile convulsions and allergic rhinitis has not been previously reported; thus, this article seeks to explore the association between these two disorders by collecting data from the Taiwanese nationwide cohort database. METHODS: A total of 1304 children with febrile convulsions were identified as the case cohort, and controls were matched based on age, sex, urbanization levels, and parents' occupation on a 1 to 4 ratio. Cox's proportional hazards regression model was used to estimate the hazard ratio and confidence interval of allergic rhinitis disorder among children with febrile convulsions. RESULTS: During an average 6.7 years follow-up period, the incidence of allergic rhinitis in the febrile convulsions case group was higher (65.16 vs 51.45 per 1000 person-years). After 11 years of follow-up, the allergic rhinitis incidence in the febrile convulsion patients was approximate 4% higher than controls (log-rank test P < 0.0001). Risk of allergic rhinitis in the febrile convulsions group was found to be 1.21 times higher than in the control group (95% confidence interval, 1.08-1.36). This risk of allergic rhinitis development is further increased (0.94 vs 18.9) with frequency of febrile convulsions-related medical visits (one to three visits vs more than three visits, P < 0.0001). CONCLUSION: Febrile convulsions may be associated with allergic rhinitis occurrence in children. Children with more than three febrile convulsion-related medical visits had a significantly higher cumulative incidence of allergic rhinitis. Both disorders have previously been reported to have similar cytokine profiles and specific viral infection association. More studies are required to explore a possible link between the two disorders.

Evaluation of the effect of Lactobacillus paracasei (HF.A00232) in children (6-13 years old) with perennial allergic rhinitis: a 12-week, double-blind, randomized, placebo-controlled study.

INTRODUCTION: Dietary supplementation with probiotics alters intestinal microflora of children and may have immunomodulatory effects in prevention of allergic diseases. The aim of this study was to evaluate the effects of Lactobacillus paracasei (LP), strain HF.A00232, as a supplementary agent to levocetirizine in treating children with perennial allergic rhinitis (AR). METHODS: This study was a 12-week, double-blind, randomized, placebo-controlled trial. Sixty children with AR aged 6-13 years with nasal total symptoms score (NTSS) ≥5 who fulfilled the inclusion criteria were enrolled. Patients were randomized into two groups with 28 participants receiving levocetirizine plus placebo and 32 participants receiving regular levocetirizine plus LP (HF.A00232) for the first 8 weeks, with a shift to levocetirizine as rescue treatment during the following 4 weeks. Parameters evaluated, including nasal, throat, and eye TSS (NTSS, TTSS, and ETSS, respectively), TSS and levocetirizine use, were recorded daily. Physical examinations and Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs) were administered at each visit. In addition, blood samples were obtained for evaluation of cytokines including interleukin-4, interferon-γ, interleukin-10, and transforming growth factor-ß at baseline, Week 8, and Week 12. RESULTS: The LP (HF.A00232) group had significantly lower PRQLQ scores even after discontinuing regular levocetirizine from Week 9 to Week 12 (p < 0.01). There was more improvement in individual parameters in the PRQLQ, including sneezing (p = 0.005), itchy nose (p = 0.040), and swollen puffy eyes (p = 0.038), in the LP (HF.A00232) group. No significant differences in TSS, NTSS, TTSS, ETSS, or cytokine levels were found between the two groups. CONCLUSION: Dietary supplementation with LP (HF.A00232) provided no additional benefit when used with regular levocetirizine in treating AR in the initial 8 weeks of our study, but there was a continuing decrease in PRQLQ scores, as well as a significant improvement in individual symptoms of sneezing, itchy nose, and swollen eyes, after discontinuing regular levocetirizine treatment.

Intraabdominal mass as presentation of colonic mucormycosis in a child with acute lymphoblastic leukemia.

Gastrointestinal mucormycosis with clinical presentation as an abdominal mass has been rarely reported in the current literature. In this observation, We report an unusual case of a child with acute lymphoblastic leukemia and neutropenic fever. During hospitalization, increasing abdominal pain and distension occurred, and initially treatments with broad-spectrum antibiotics were administered. However, the symptoms/signs progressed with the development of peritonitis and a palpated mass over the right lower quarter of the abdomen. Imaging studies showed ascending colon perforation with abscess formation. Right hemicolectomy was performed and colonic mucormycosis was confirmed on histologic examination and ascitic fluid culture. Immediately, intravenous liposomal amphotericin B was administered but the clinical condition rapidly deteriorated and the patient expired despite treatment.