Research Progress of Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease first discovered in Ta-pieh Mountains in central China in 2009. It is caused by a novel bunyavirus infection (SFTSV). Since the first discovery of SFTSV, there have been case reports and epidemiological studies on SFTS in several East Asian countries, such as South Korea, Japan, Vietnam and so on. With the rising incidence of SFTS and the rapid spread of the novel bunyavirus around the world, it is clear that the virus has a pandemic potential and may pose a threat to global public health in the future. Early studies have suggested that ticks are an important medium for the transmission of SFTSV to humans; in recent years, it has been reported that there is also human-to-human transmission. In endemic areas, potential hosts include a variety of livestock and wildlife. When people are infected with SFTV, the main clinical manifestations are high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, liver and kidney function damage, and even MODS, with a mortality rate of about 10-30%. This article reviews the latest progress of novel bunyavirus, including virus transmission vector, virus genotypic diversity and epidemiology, pathogenesis, clinical manifestation and treatment.

Invasive lobular carcinoma enclosed by a benign phyllodes tumor: A case report.

INTRODUCTION AND IMPORTANCE: Phyllodes tumors (PT) account for approximately 1% of all breast tumors. The coexistence of phyllodes tumor and invasive lobular carcinoma in the ipsilateral breast is extremely rare with fewer than six cases reported worldwide in the last 20 years. We hereby present the first in Taiwan. CASE PRESENTATION: A 43-year-old female was presented with a protruding tumor with bleeding tendency over left breast in 2016. Breast sonography revealed highly suspected malignancy (ACR BI-RADS category 5). Computed tomography scan disclosed a protruding mass occupying the left breast. Core needle biopsy showed a fibroepithelial lesion favoring fibroadenoma. Considering clinicopathological discrepancy, a nipple-sparing mastectomy was conducted. Pathology report revealed a benign PT with an incidental finding of invasive lobular carcinoma (pT1cN0) within the tumor. Due to tumor recurrence, the patient received re-operation of total mastectomy in 2017, and is under regular adjuvant hormonal therapy without cancer recurrence to date. CLINICAL DISCUSSION: Physicians could easily overlook carcinomas enclosed by PTs due to its occult property. However, when carcinomatous changes arise from within or along with the PT, the proposed therapeutical course may be altered. Moreover, invasive carcinoma components in PTs possess potential for lymph node metastasis. Multidisciplinary cooperation is key in detecting and managing PT with synchronous carcinomatosis. CONCLUSION: Thorough examination of the excised tumor specimen and ensuring an adequate surgical margin is necessary. Sentinel lymph node biopsy (SLNB) should be considered whenever suspicious clinical features occur in PT patients. This may aid in the detection of microscopic invasive carcinomatous change.

Environmental behavior, human health effect, and pollution control of heavy metal(loid)s toward full life cycle processes.

Heavy metal(loid)s (HMs) have caused serious environmental pollution and health risks. Although the past few years have witnessed the achievements of studies on environmental behavior of HMs, the related toxicity mechanisms, and pollution control, their relationship remains a mystery. Researchers generally focused on one topic independently without comprehensive considerations due to the knowledge gap between environmental science and human health. Indeed, the full life cycle control of HMs is crucial and should be reconsidered with the combination of the occurrence, transport, and fate of HMs in the environment. Therefore, we started by reviewing the environmental behaviors of HMs which are affected by a variety of natural factors as well as their physicochemical properties. Furthermore, the related toxicity mechanisms were discussed according to exposure route, toxicity mechanism, and adverse consequences. In addition, the current state-of-the-art of available technologies for pollution control of HMs wastewater and solid wastes were summarized. Finally, based on the research trend, we proposed that advanced in-operando characterizations will help us better understand the fundamental reaction mechanisms, and big data analysis approaches will aid in establishing the prediction model for risk management.

Cord Blood Soluble CD14 Predicts Wheeze and Prolonged Cough in Young Children: The PATCH Study.

BACKGROUND: Soluble cluster of differentiation 14 (sCD14) plays a role in the development and manifestation of atopic symptoms, although the results of previous studies have been inconclusive. The aim of this study is to evaluate the practical use of sCD14 as a predictive biomarker of allergy in young children. METHODS: Children aged 0-1 year from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Cord blood sCD14 concentrations were measured. Pediatrician evaluation and questionnaire interviews were performed periodically until 1 year of age to determine the children's allergic and respiratory symptoms. RESULTS: Two hundred and six 1-year-old subjects were enrolled. Wheeze was positively associated with cord blood sCD14, a family member with asthma and parental smoking. Prolonged cough was associated with cord blood sCD14, older maternal age and more siblings. In the multivariate logistic regression analysis, cord blood sCD14 was the only independent predictive biomarker for wheeze and prolonged cough by 1 year of age. Every 100-ng/ml increase in cord blood sCD14 resulted in a 1.56-fold higher risk of developing wheeze and a 1.62-fold higher risk of prolonged cough in children by 1 year of age. CONCLUSIONS: Cord blood sCD14 may be a useful biomarker for predicting infant wheeze and prolonged cough by 1 year of age.

Urinary LTE4 levels as a diagnostic marker for IgE-mediated asthma in preschool children: a birth cohort study.

OBJECTIVES: Leukotrienes play a central pathophysiological role in allergic asthma. The aim of this study was to investigate the utility of measuring urinary leukotriene E4 (LTE4) levels in the diagnosis of atopic diseases in early childhood. METHODS: Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Urinary LTE4 levels were measured and its association between total serum IgE levels, allergen-specific IgE sensitization and atopic diseases were assessed. RESULTS: A total of 182 children were regular followed up at clinics for a four-year follow-up period. Urinary LTE4 levels appeared to be elevated in children with total serum IgE levels exceeding 100 kU/L, allergen-specific IgE sensitization after 2 years of age. Elevation of urinary LTE4 levels (≥500 pg/mg of creatinine) significantly discriminated high serum total IgE levels (≥100 kU/L) at age 2 (P = 0.027). A higher level of total serum IgE or urinary LTE4 was significantly associated with the risk of developing allergic rhinitis and asthma at age 3. A significantly higher urinary LTE4 level was found in children with a combination of IgE sensitization and asthma at age 4. CONCLUSIONS: Urinary LTE4 levels appear to be highly associated with IgE sensitization and its related allergic airway diseases after age 2. The measurement of urinary LTE4 (≥500 pg/mg of creatinine) could not only be a non-invasive method for atopic predisposition but also potentially provide a strategy for the diagnosis and management of asthma in preschool children.

Low cord blood vitamin D levels are associated with increased milk sensitization in early childhood.

BACKGROUND: The association between vitamin D status at birth and allergen sensitizations is uncertain. The aim of this study was to investigate the relationship between cord blood vitamin D status with allergen sensitizations and the development of atopic diseases in early childhood. METHODS: Children aged 0 through 4 yr from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Serum levels of 25-hydroxyvitamin D (25(OH)D) in cord blood were measured by a new automated electrochemiluminescence-based assay. Specific IgE antibodies against food and inhalant allergens were measured at 6 months, and 1, 1.5, 2, 3, and 4 yr of age. RESULTS: A total of 186 children were regular followed up at clinics for a 4-yr follow-up period. The mean level of cord blood 25(OH)D was 23.8 ± 9.5 ng/ml with a high prevalence of low vitamin D status (<20 ng/ml) at birth (42%). There was a tendency of low cord blood 25(OH)D levels being associated with higher risk of food sensitization throughout childhood. Cord blood 25(OH)D levels were inversely associated with the risk of milk sensitization at age 2, at which age a higher prevalence of milk sensitization was significantly associated with the risk of allergic rhinitis, and asthma development at age 4. CONCLUSIONS: Low cord blood vitamin D levels appear to be associated with increased milk sensitization but not with asthma, eczema, or allergic rhinitis in early childhood.

Serum 25-hydroxyvitamin D levels in relation to lung function and exhaled nitric oxide in children.

OBJECTIVE: To investigate the relationship of vitamin D status with lung function and fraction of exhaled nitric oxide (FeNO) in a population sample of children. STUDY DESIGN: A total of 1315 children aged 5-18 years were evaluated using serum 25-hydroxyvitamin D [25(OH)D] levels, spirometry, a single-breath online FeNO measurement, and questionnaires. RESULTS: After adjusting for confounders, the mean forced vital capacity was 53.4 mL (SE, 26.5 mL; P = .045), and the mean forced expiratory volume in 1 second was 48.2 mL (SE, 23.6 mL; P = .042) lower for children with insufficient serum 25(OH)D levels (20-29.9 ng/mL) compared with those with sufficient 25(OH)D levels (≥30 ng/mL). The mean difference between children with deficient (<20 ng/mL) and sufficient levels of serum 25(OH)D was 81.9 mL (SE, 26.7 mL; P = .002) for forced vital capacity and 55.2 mL (SE, 23.7 mL; P = .020) for forced expiratory volume in 1 second. There was no significant association between serum 25(OH)D levels and FeNO after adjusting for confounders. CONCLUSIONS: Our results demonstrate a significant relationship between insufficient serum vitamin D levels and worse lung function in children in the community with a suggested dose-response effect. Our findings also suggest that vitamin D status is not a significant determinant of FeNO in children in the general population.

Sensitization to food and inhalant allergens in relation to atopic diseases in early childhood: a birth cohort study.

OBJECTIVES: A correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood. METHODS: Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Specific IgE antibody against food and inhalant allergens were measured and their association between total serum IgE levels and atopic diseases were assessed. RESULTS: A total of 182 children were regular followed up at clinics for a four-year follow-up period. The prevalence of food allergen sensitization increased markedly after 6 months of age, reaching up to 47% at 1.5 years of age and then declined significantly to 10% in parallel with a considerable increase in the prevalence of sensitization to inhalant allergens up to 25% at age 4. Food allergen sensitization appeared to be mainly associated with the elevation of serum total IgE levels before age 2. A combined sensitization to food and inhalant allergens had an additive effect on serum IgE levels after age 2, and was significantly associated with the risk of developing atopic diseases at age 4. CONCLUSIONS: Sensitization to food occurs early in life, in parallel with the rising prevalence of sensitization to inhalant allergens at older age. A combined sensitization to food and inhalant allergens not only has an additive increase in serum IgE antibody production but also increases the risk of developing allergic respiratory diseases in early childhood.

Suboptimal vitamin D status in a population-based study of Asian children: prevalence and relation to allergic diseases and atopy.

BACKGROUND: New evidence shows high prevalence of vitamin D deficiency in many countries and some studies suggest a possible link between vitamin D status and allergic diseases. The objectives of this study were to determine the prevalence of suboptimal vitamin D status in a population sample of Asian children and to investigate the relationship of vitamin D status with allergic diseases and atopy. METHODS: Children aged 5-18 years (N = 1315) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were evaluated using questionnaires, anthropometric measurements, and serum levels of 25-hydroxyvitamin D [25(OH)D] and total and specific immunoglobulin E (IgE). RESULTS: The mean concentration of serum 25(OH)D was 20.4 ng/mL (SD: 7.1 ng/mL). Vitamin D deficiency (defined as serum 25(OH)D<20 ng/mL) was present in 670 subjects (51.0%), while vitamin D insufficiency (defined as serum 25(OH)D<30 ng/mL) was observed in 1187 subjects (90.3%). Older age (P<0.001), female gender (P<0.001), higher body mass index (P = 0.001), winter and spring seasons (compared to summer; P both<0.001), and passive smoking (P = 0.011) were independently associated with low serum 25(OH)D levels. After adjusting for potential confounders, serum 25(OH)D status had no association with asthma, rhinitis, eczema, atopy, or total serum IgE (all P>0.05). CONCLUSIONS: Low serum 25(OH)D levels are remarkably common in this population sample of Asian children, suggesting that millions of children living in Taiwan may have suboptimal levels of vitamin D, which should be a matter of public health concern. Our results provides epidemiological evidence against the association of vitamin D status with various allergic diseases and atopy in Asian children.

Life-threatening pneumonitis complicating low-dose methotrexate treatment for juvenile idiopathic arthritis in a child.

Methotrexate, a drug commonly used to treat juvenile idiopathic arthritis (JIA), has been reported to cause interstitial pneumonitis as a rare complication in adults with rheumatoid arthritis. Only 1 suspicious case of methotrexate pneumonitis in a child with JIA has been reported in 1998, though with no histopathologic proof. Given its rarity and nonspecific presenting symptoms, diagnosis may be challenging, and a life-threatening illness can occur without a high index of suspicion, as illustrated by this report of a 13-year-old girl with JIA who developed fever, nonproductive cough, and dyspnea as presenting features of interstitial pneumonitis after 1 year of methotrexate therapy. Chest high-resolution computed tomography revealed patchy ground-glass opacities and interlobular septal thickening without pleural effusion. Lung biopsy showed interstitial pneumonitis with diffuse alveolar damage. The symptoms and radiographs improved dramatically after withdrawal of methotrexate and administration of corticosteroids. A restrictive ventilatory defect with decreased diffusion capacity on pulmonary function testing persisted until 20 months after methotrexate withdrawal. There is no single pathognomic feature for methotrexate pneumonitis; rather, diagnosis relies on a constellation of clinical, radiologic, and pathologic findings. This report highlights the necessity for pediatricians to be continuously vigilant for interstitial pneumonitis in children receiving methotrexate who develop new unexplained pulmonary symptoms.

Total serum IgE in a population-based study of Asian children in Taiwan: reference value and significance in the diagnosis of allergy.

BACKGROUND: Total serum immunoglobulin (IgE) test is usually performed to aid in the diagnosis of allergic diseases, but its reference values may vary among people of different ethnic backgrounds. OBJECTIVES: To establish reference values of total IgE in Asian children and to assess their significance in the diagnosis of atopy and allergic diseases. STUDY DESIGN: 1321 Asian children aged 5-18 years in the Prediction of Allergies in Taiwanese CHildren (PATCH) study, a population-based cohort, were evaluated for total and specific IgE by ImmunoCAP and Phadiatop Infant, respectively. RESULTS: Male, atopy, allergic diseases, recent symptoms of upper respiratory infection, and lower FEV1/FVC, were associated with higher total IgE levels in univariate analyses. Multivariate analysis revealed that atopy was the single most important determinant explaining 66.1% of the variability of total IgE levels in this population. The area under the receiver-operator characteristic (ROC) curve of total IgE for diagnosing atopy, asthma, rhinitis, and eczema were 0.92, 0.72, 0.70, and 0.70, respectively. The sensitivity, specificity, and positive and negative predictive values of total IgE at the optimal cutoff of 77.7 kU/L on the ROC curve for diagnosing atopy were 82.3%, 87.1%, 89.5%, and 78.6%, respectively. The corresponding values using the upper 95% CI of total IgE (164.3 kU/L) in non-atopic children were 61.2%, 95.0%, 94.3%, and 64.6%, respectively; whereas a customary cutoff (100 kU/L) provided accuracy between that of the aforementioned two cutoffs. Total IgE at the cutoff of 77.7 kU/L provided modest sensitivity and specificity (49.0%-78.3%) for diagnosing allergic diseases, but had high negative predictive values (84.2%-97.9%). CONCLUSIONS: Total serum IgE discriminates Asian children with and without atopy independent of allergic symptoms, with an optimal cutoff of 77.7 kU/L. The study confirms the insufficient diagnostic accuracy of total IgE alone to detect allergic diseases, but low total IgE levels may help exclude allergic diseases.

Differences in disease features between childhood-onset and adult-onset systemic lupus erythematosus patients presenting with acute abdominal pain.

OBJECTIVE: Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain. METHODS: A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain. RESULTS: The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P < 0.001) at the time of admission. The overall case fatality rate of acute abdomen in SLE patients was 9.4%. The extra-gastrointestinal symptoms, laboratory evaluation, disease activity, and organ damage measured by the SLE Disease Activity Index and outcomes were comparable between children and adults. CONCLUSIONS: Various etiologies of acute abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen.

Occult pulmonary hemorrhage as a rare presentation of propylthiouracil-induced vasculitis.

Propylthiouracil, a drug commonly used to treat hyperthyroidism, is known to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis as a rare complication. The wide clinical spectrum of propylthiouracil-induced vasculitis ranges from mild forms with rash and/or arthralgia to severe forms with renal or pulmonary involvement, which can be critical and life-threatening if left unrecognized and untreated. Given its rarity and exceedingly variable clinical presentations, diagnosis may be challenging, and delayed diagnosis is not uncommon without a high index of suspicion, as illustrated by this report of a 17-year-old girl with Graves' disease who developed occult pulmonary hemorrhage as an overlooked rare presentation of ANCA-associated vasculitis after administration of propylthiouracil. Associated clinical features included fever, fatigue, palpable purpura, polyarthritis, and nephritis. Positive findings on chest radiography prompted the bronchoalveolar lavage procedure, which led to the identification of pulmonary hemorrhage. Skin biopsy showed leukocytoclastic vasculitis. Serologic test results were positive for perinuclear ANCA, cytoplasmic ANCA, myeloperoxidase-ANCA, proteinase 3-ANCA, and cryoglobulins but negative for antinuclear antibody, anti-double-stranded DNA, rheumatoid factor, and anti-hepatitis C virus antibody. The symptoms resolved after discontinuation of propylthiouracil and a few months of corticosteroids and azathioprine. This report highlights the necessity for physicians to keep alert for the protean manifestations of propylthiouracil-induced vasculitis.