Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications.

Toll-like receptors (TLRs) are vital components of the innate immune system, serving as the first line of defense against pathogens by recognizing a wide array of molecular patterns. This review summarizes the critical roles of TLRs in immune surveillance and disease pathogenesis, focusing on their structure, signaling pathways, and implications in various disorders. We discuss the molecular intricacies of TLRs, including their ligand specificity, signaling cascades, and the functional consequences of their activation. The involvement of TLRs in infectious diseases, autoimmunity, chronic inflammation, and cancer is explored, highlighting their potential as therapeutic targets. We also examine recent advancements in TLR research, such as the development of specific agonists and antagonists, and their application in immunotherapy and vaccine development. Furthermore, we address the challenges and controversies surrounding TLR research and outline future directions, including the integration of computational modeling and personalized medicine approaches. In conclusion, TLRs represent a promising frontier in medical research, with the potential to significantly impact the development of novel therapeutic strategies for a wide range of diseases.

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.

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.

Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department.

BACKGROUND: Croup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited. The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). POPULATION AND METHOD: Patients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. RESULT: In total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842-0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711-0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. CONCLUSION: NLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

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.

Survey of knowledge, self-efficacy, and attitudes toward suicide prevention among nursing staff.

OBJECTIVE: This study aimed to explore the knowledge, self-efficacy, and attitudes toward suicide prevention among nurses with different demographic characteristics. METHODS: A cross-sectional descriptive design was adopted, and the study was conducted between August and September 2020. The content of the questionnaire included basic demographics, knowledge, self-efficacy, and attitudes toward suicide prevention. Correlation analysis was performed to determine nurses' knowledge, self-efficacy, and attitudes toward suicide prevention. RESULTS: The sample comprised 778 nursing staff from a medical center in southern Taiwan. The results showed that age, years of nursing experience, department type, education on suicide prevention, and care experience of nursing staff were associated with their knowledge, self-efficacy, and attitudes toward suicide prevention in general hospital patients. Younger and less experienced nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Nurses who received suicide-related education and training exhibited better self-efficacy and attitudes than those who did not. Nurses with care experience had better knowledge of suicide prevention than those without experience. Knowledge and self-efficacy in suicide prevention were both significantly and positively correlated with attitudes. CONCLUSION: Younger, less experienced, psychiatric nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Therefore, education on suicide prevention should be strengthened for older, experienced, and non-psychiatric nurses.

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.

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.

Predictive value of the Distress Thermometer score for risk of suicide in patients with cancer.

PURPOSE: This study aimed to assess the association between the Distress Thermometer (DT) score and risk of suicide in patients with cancer. In addition, we aimed to determine the best cutoff score to predict patients at risk of suicide. METHODS: From 2015 to 2016, we retrospectively collected data on patients with cancer. DT scores were collected, and the association between DT score and risk of suicide (suicide ideation or death ideation) was analyzed. Furthermore, receiver operating characteristic (ROC) analysis was performed to identify the appropriate cutoff score for predicting risk of suicide. RESULTS: A total of 260 patients with cancer were included, and suicidal ideation was identified in 33 cases referred for psychological intervention. The DT scores of the patients with suicidal ideation were significantly higher than those of patients without suicidal ideation (6.30±2.11 vs. 4.29±1.72, p<0.05). In addition, the area under the ROC curve for predicting risk for suicide was 0.758. The cutoff DT score of 3 had the highest sensitivity of 1.00 to rule out suicidal ideation, while 9 had the highest specificity of 1.00 to rule in suicidal ideation. Moreover, the appropriate cutoff DT score to predict patients with suicidal ideation was 5, with a sensitivity of 0.52, specificity of .84, positive likelihood ratio of 3.24, and negative likelihood ratio of 0.58. CONCLUSION: The DT score may be a helpful clinical tool to evaluate emotional distress and risk of suicide in patients with cancer. Clinically, for DT scores greater than 5 in patients with cancer, the risk of suicide greatly increases. In view of the DT's widespread use internationally by non-mental health clinicians in cancer to guide the need for specialist mental health interventions, its potential utility in also predicting suicide risk is of great interest.

Optimal initial antibiotic regimen for the treatment of acute appendicitis: a systematic review and network meta-analysis with surgical intervention as the common comparator.

BACKGROUND: The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens. METHODS: We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a ß-lactam/ß-lactamase inhibitor combination. RESULTS: A total of 9 RCTs (adults, n = 8; paediatrics, n = 1) and 12 observational studies (adults, n = 3; paediatrics, n = 9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a ß-lactam/ß-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8-127.64] or ß-lactam/ß-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87-187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55-38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01-0.85). CONCLUSIONS: Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.

Vascular Reactivity Index as an Effective Predictor of Mortality in Children With Refractory Septic Shock.

BACKGROUND: Vasoplegia is vascular hyporesponsiveness to vasopressors and is an important phenomenon in children with refractory septic shock. This study aimed to develop an objective formula correlated with vasoplegia and evaluate the predictive power for mortality in children with refractory septic shock. MATERIALS AND METHODS: We retrospectively analyzed children with refractory septic shock admitted to a pediatric intensive care unit (PICU) and monitored their hemodynamics via a pulse index continuous cardiac output (PiCCO) system. Serial hemodynamic data including cardiac index (CI), systemic vascular resistant index (SVRI) and vasoactive-inotropic score (VIS) were recorded during the first 72 hours after PICU admission. We defined vascular reactivity index (VRI) as SVRI/VIS and analyzed the effect of VRI in predicting mortality in children with refractory septic shock. RESULTS: Thirty-three children with refractory septic shock were enrolled. The SVRI was lower in the mortality group compared to the survival group (P < .05). The average area under the receiver operating characteristic curve of VRI within the first 72 hours was 0.8 and the serial values of VRI were significantly lower in the mortality group during the period from 0 to 48 hours (P < .05). However, there were no significant differences in serial CI values between the survival and mortality groups. CONCLUSIONS: Vasoactive-inotropic score may potentially be used to quantify the severity of vasoplegia based on the clinical response of vessels after resuscitation with vasopressors. Lower VRI levels may indicate a higher risk of mortality in children with septic shock.

Occult child abuse presenting as pneumatosis intestinalis and portomesenteric venous gas - a case report.

BACKGROUND: Pneumatosis intestinalis and portomesenteric venous gas are usually caused by necrotizing enterocolitis; however they can occur secondary to abusive abdominal trauma with bone fractures and bruising. It is difficult to recognize initially if there is no bruising on the skin or bone fractures. CASE PRESENTATION: We report a 1-year-old child with no obvious history of trauma who presented with conscious disturbance. Abdominal computed tomography showed acute ischemic bowel complicated with pneumatosis intestinalis and portomesenteric venous gas. The first impression was septic shock with acute ischemic bowel. Two weeks after admission, brain magnetic resonance imaging showed subdural hemorrhage of different stages over bilateral fronto-parietal convexities and diffuse axonal injury, suggesting abusive head trauma. He was subsequently diagnosed with occult child abuse. CONCLUSION: Pneumatosis intestinalis and portomesenteric venous gas are rare except in cases of prematurity. Occult abusive abdominal trauma should be considered as a differential diagnosis in patients with pneumatosis intestinalis and portomesenteric venous gas, even without any trauma on the skin or bone fractures.

Effectiveness of Parenteral Glutamine on Methotrexate-induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia.

High-dose methotrexate (HDMTX) is important for children with acute lymphoblastic leukemia (ALL). There is no effective treatment for patients with oral mucositis, which is a major side effect associated with HDMTX. Here, we reviewed the medical records of patients younger than 18 yr with newly diagnosed ALL in our hospitals from 2002 to 2013. According to the nationwide protocol (TPOG-ALL-2002), each patient received four courses of HDMTX (2.5 or 5 g/m2) during consolidation therapy. HDMTX courses with glutamine therapy were as the glutamine group, and intravenous glutamine (0.4 g/kg/day) was started within 48 h after the initiation of HDMTX for 3 consecutive days. HDMTX courses without glutamine were as the control group. A total of 347 HDMTX courses were administrated in the 96 children with ALL during the study period. The incidence of oral mucositis was significantly lower in the glutamine group than in the control group (3.8% vs. 17.6%; P = 0.004). In the glutamine group, no patients suffered from severe oral mucositis. No severe adverse effects associated with glutamine administration were noted. Accordingly, parenteral glutamine appears to be feasible and safe to prevent oral mucositis in patients receiving HDMTX.

Survival and complication rates in patients with thalassemia major in Taiwan.

BACKGROUND: While transfusion and iron chelation therapy for thalassemia major (TM) has improved dramatically in recent years, the consequences of this improvement (current rates of survival and TM-related complications) remain unknown. METHODS: This nationwide population-based cohort study analyzed 2007-2011 data obtained from the Taiwanese National Health Insurance Research Database. RESULTS: After excluding those patients receiving hematopoietic stem cell transplantation, we enrolled 454 patients with TM who received transfusion and chelation therapy (median age, 17.2 years). Among these patients, the mortality rate was 2.9% in 2007, 2.3% in 2008, 2.9% in 2009, 2.6% in 2010, and 0.7% in 2011. Heart was the most common target organ of TM-related complications. There were 80 patients (17.6%) with arrhythmia and 86 patients (18.9%) with congestive heart failure. Dysfunction of endocrine organs was common, and the most common endocrinopathy was hypogonadism (23.1%), followed by diabetes (21.2%). There were 75 patients (16.5%) with liver cirrhosis and 79 patients (17.4%) with osteoporosis. CONCLUSIONS: Adequate red blood cell transfusion and iron chelation is available to all patients with TM in Taiwan under the universal health insurance system, and has resulted in reduction of TM-related mortality to very low levels. As these patients get older, early detection of complications and adequate intervention are important to quality-of-life improvement.

Chronic kidney disease and diabetes associated with long-term outcomes in patients receiving percutaneous coronary intervention.

BACKGROUND: The effect of diabetes mellitus (DM) and chronic kidney disease (CKD) on long-term outcomes in patients receiving percutaneous coronary intervention (PCI) is unclear. METHODS: A total of 1394 patients who underwent PCI were prospectively enrolled and divided into 4 groups according to the presence or absence of DM or CKD. Baseline characteristics, risk factors, medications, and angiographic findings were compared. Determinants of long-term outcomes in patients undergoing PCI were analyzed. RESULTS: Patients with DM and CKD had the highest all-cause mortality and cardiovascular mortality (both P < 0.01) but there were no differences existed in myocardial infarction (MI) or repeated PCI among the 4 groups (P = 0.19, P = 0.87, respectively). Patients with DM and CKD had the lowest even-free rate of all-cause mortality, cardiovascular mortality, MI, and repeated PCI (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). In the Cox proportional hazard model, patients with both DM and CKD had the highest risk of all-cause mortality (HR: 3.25, 95% CI: 1.85-5.59), cardiovascular mortality (HR: 3.58, 95% CI: 1.97-6.49), MI (HR: 2.43, 95% CI: 1.23-4.08), and repeated PCI (HR: 1.79, 95% CI: 1.33-2.41). Patients with CKD alone had the second highest risk of all-cause mortality (HR: 2.04, 95% CI: 1.15-3.63), cardiovascular mortality (HR: 2.13, 95% CI: 1.13-4.01), and repeated PCI (HR: 1.47, 95% CI: 1.09-1.97). CONCLUSIONS: DM and CKD had additive effect on adverse long-term outcomes in patients receiving PCI; CKD was a more significant adverse predictor than DM.

Impact of diabetes and hypertension on cardiovascular outcomes in patients with coronary artery disease receiving percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is a necessary procedure commonly performed for patients with coronary artery disease (CAD). However, the impact of diabetes and hypertension on long-term outcomes of patients after receiving PCI has not yet been determined. METHODS: The data of 1234 patients who received PCI were collected prospectively, and patients were divided into four groups, including patients with and without DM and those with either DM or hypertension alone. Baseline characteristics, risk factors, medications and angiographic findings were compared and determinants of cardiovascular outcomes were analyzed in patients who received PCI. RESULTS: Patients with DM alone had the highest all-cause mortality (P < 0.001), cardiovascular mortality and myocardial infarctions (MI) (both P < 0.01) compared to the other groups. However, no differences were found between groups in repeat PCI (P = 0.32). Cox proportional hazard model revealed that age, chronic kidney disease (CKD), previous MI and stroke history were risk factors for all-cause mortality (OR: 1.05,1.89, 2.87, and 4.12, respectively), and use of beta-blockers (BB) and statins reduced all-cause mortality (OR: 0.47 and 0.35, respectively). Previous MI and stroke history, P2Y12 inhibitor use, and syntax scores all predicted CV mortality (OR: 4.02, 1.89, 2.87, and 1.04, respectively). Use of angiotensin converting enzyme inhibitors (ACEI), beta-blockers (BB), and statins appeared to reduce risk of CV death (OR: 0.37, 0.33, and 0.32, respectively). Previous MI and syntax scores predicted MI (OR: 3.17 and 1.03, respectively), and statin use reduced risk of MI (OR: 0.43). Smoking and BB use were associated with repeat PCI (OR: 1.48 and 1.56, respectively). CONCLUSIONS: After PCI, patients with DM alone have higher mortality compared to patients without DM and hypertension, with both DM and hypertension, and with hypertension alone. Comorbid hypertension does not appear to increase risk in DM patients, whereas comorbid DM appears to increase risk in hypertensive patients. TRIAL REGISTRATION: REC103-15 IRB of Taichung Tzu-chi Hospital.

Clinical assessment of children with renal abscesses presenting to the pediatric emergency department.

BACKGROUND: Renal abscesses are relatively uncommon in children but may result in prolonged hospital stays and life-threatening events. We undertook this study to analyze the clinical spectrum of renal abscesses in children admitted to the pediatric emergency department (ED) and to find helpful clinical characteristics that can potentially aid emergency physicians for detecting renal abscesses in children earlier. METHODS: From 2004 to 2011, we retrospectively analyzed 17 patients, aged 18 years or younger, with a definite diagnosis of renal abscess admitted to the ED. The following clinical information was studied: demographics, clinical presentation, laboratory testing, microbiology, imaging studies, treatment modalities, complications, and long-term outcomes. We analyzed these variables among other potential predisposing factors. RESULTS: During the 8-year study period, 17 patients (7 males and 10 females; mean age, 6.1 ± 4.5 years) were diagnosed with renal abscesses on the basis of ultrasonography and computed tomography findings. The 2 most common presenting symptoms were fever and flank pain (100% and 70.6%, respectively). All of the patients presented with leukocytosis and elevated C-reactive protein (CRP) levels. Organisms cultured from urine or from the abscess were identified in 11 (64.7%) patients, and Escherichia coli was the most common organism cultured. All patients were treated with broad-spectrum intravenous antibiotics with the exception of 4 children who also required additional percutaneous drainage of the abscess. CONCLUSIONS: Renal abscesses are relatively rare in children. We suggest that primary care physicians should keep this disease in mind especially when children present with triad symptoms (fever, nausea/vomiting, and flank pain), pyuria, significant leukocytosis, and elevated CRP levels. However, aggressive percutaneous drainage may not need to be routinely performed in children with renal abscesses.

Downregulated CXCL12 expression in mesenchymal stem cells associated with severe aplastic anemia in children.

The mechanisms of idiopathic severe aplastic anemia (SAA) in children are not completely understood. Insufficiency of the bone marrow microenvironment, in which mesenchymal stem cells (MSCs) are an important element, can be a potential factor associated with hematopoietic impairment. In the current study, we studied whether aberrant gene expression could be found in MSCs from children with SAA. Using microarray analysis, two different patterns of global gene expression were detected in the SAA MSCs. Fourteen genes (POLE2, HGF, KIF20A, TK1, IL18R1, KITLG, FGF18, RRM2, TTK, CXCL12, DLG7, TOP2A, NUF2, and TYMS), which are related to DNA synthesis, cytokines, or growth factors, were significantly downregulated. Further, knockdown of gene expression was performed using the small hairpin RNA (shRNA)-containing lentivirus method. We found that knockdown of CXCL12, HGF, IL-18R1, FGF18, or RRM2 expression compelled MSCs from the controls to behave like those from the SAA children, with decreased survival and differentiation potential. Among them, inhibition of CXCL12 gene expression had the most profound effects on the behavior of MSCs. Further experiments regarding re-introduction of the CXCL12 gene could largely recover the survival and differentiation potential in MSCs with inhibition of CXCL12 expression. Our findings suggest that MSCs from children with SAA exhibit aberrant gene expression profiles and downregulation of CXCL12 gene may be associated with alterations in the bone marrow microenvironment.

Recurrent Streptococcus Pneumoniae 23 F meningitis due to cerebrospinal fluid leakage from the ear cannel: a case report.

BACKGROUND: Bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to establish the specific cause. Recurrence of bacterial meningitis in children is not only potentially life-threatening, but also involves or induces psychological trauma to the patients through repeated hospitalization with many invasive investigations. CASE PRESENTATION: A 6-year-old boy was diagnosed with recurrent bacterial meningitis caused by Streptococcus Pneumonia 23 F. He had received serial imaging studies for identifying the cause. The initial sinus computed tomography (CT) also showed sinusitis without bony defect of sinus. However, after performing nuclear scan, the results showed cerebrospinal fluid (CSF) leaked originating from the right petrooccpital region into the middle ear. Subsequent high resolution CT (HRCT) reports showed focal enlargement of the right facial nerve canal, erosion of the bony canal at geniculate ganglion and tympanic segment with tiny high-density spots. The reconstruction HRCT showed multiple bony defects at temporal bone. The magnetic resonance imaging revealed multifocal bony destruction with CSF collection in the right petrous ridge, carotid canal and jugular foramen. Eventually, CSF leakage to the right middle ear was confirmed and this could be the cause of the recurrent bacteria meningitis in this patient. CONCLUSION: Although recurrent bacterial meningitis in childhood is not common, this case report illustrates that recurrence of meningitis within a short period should be considered as cause of underline immunologic or anatomic defect.