We studied paediatric patients with human adenovirus (HAdV) infection during the 2011 outbreak in northern Taiwan to define the clinical features of different HAdV genotypes in children.
Between ...January and December 2011, 637 patients <19 years of age exhibited culture-confirmed adenoviral infection in Chang Gung Memorial Hospital, and provided specimens available for genotyping by multiplex real-time PCR. Clinical data were collected retrospectively.
Excluding five cases with multiple genotypes, 632 cases were included for analysis. Three genotypes were identified, including HAdV-3 (429/632; 67.6%), HAdV-7 (144/632; 22.6%) and HAdV-2 (59/632; 9.8%). Median age was 4.58 years (range 2 months to 18 years), with children infected with HAdV-3 significantly older (82.9% >3 years; p <0.001). Of the 621 inpatients, 98.2% had fevers and all exhibited respiratory symptoms, 75 patients (12.1%) had lower respiratory tract infections, 20 (3.2%) required intensive care (HAdV-2: 1; HAdV-3: 8; and HAdV-7: 11), and three died (all HAdV-7-infected). HAdV-3-infected patients were significantly more likely to have upper respiratory symptoms and a high serum C-reactive protein level >100 mg/L, whereas leucocytosis (white blood cell count >15 000/mm3) was more common in HAdV-2-infected patients (p 0.007). HAdV-7 infections were significantly associated with a longer duration of fever, leucopenia (white blood cell count <5000/mm3), thrombocytopenia (platelet count <150 000/mm3), lower respiratory tract infections, a longer length of hospital stay, and requiring intensive care (all p <0.001).
Childhood HAdV-2, HAdV-3 and HAdV-7 infections may exhibit different clinical manifestations. Although HAdV-3 was the most prevalent genotype observed during the 2011 Taiwan outbreak, HAdV-7 caused more severe disease characteristics and outcomes.
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and ...stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined.
We completed a comprehensive literature ...search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed.
One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0–12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9–34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4–31.1. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01–16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ2 = 2.12, P = 0.5473).
The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.
Background Amoxicillin‐resistant Helicobacter pylori with minimal inhibitory concentration (MIC) ≥ 256 mg L−1 was isolated from a gastritis patient. The aims were to investigate the mechanism of ...high‐level amoxicillin resistance in H. pylori.
Materials and methods The β‐lactamase production was determined by means of nitrocefin sticks and the presence of gene encoding the β‐lactam antibiotic resistance enzyme TEM β‐lactamase was analysed by polymerase chain reaction (PCR), sequencing and dot‐blot hybridization. Sequencing analysis of pbp1A gene was performed and amoxicillin‐susceptible isolate was transformed with pbp1A PCR products from the resistant isolate. The expression of hefC efflux system was analysed using real‐time quantitative PCR.
Results Activity of β‐lactamase was detected. Sequence analysis showed that the PCR product derived from H. pylori 3778 was identical to the blaTEM‐1 (GenBank accession EU726527). Dot‐blot hybridization confirmed the presence of β‐lactamase gene blaTEM‐1. By transformation of PCR product of mutated pbp1A gene from H. pylori 3778 into amoxicillin‐susceptible strain showed that substitutions in Thr556→Ser, Lys648→Gln, Arg649→Lys and Arg656→Pro contribute to low‐level amoxicillin resistance. The MIC of amoxicillin for the transformants was 0·75 mg L−1. Over‐expression of hefC was not found.
Conclusions High‐level amoxicillin resistance is associated with β‐lactamase production in H. pylori. Low‐level amoxicillin resistance is linked to a point mutation on pbp1A. Because H. pylori can exchange DNA through natural transformation, spreading of blaTEM‐1 amoxicillin resistance gene among H. pylori is a potential threat when treating H. pylori infection.
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its ...stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.
The strong coupling between antiferromagnetism and ferroelectricity at room temperature found in BiFeO3 generates high expectations for the design and development of technological devices with novel ...functionalities. However, the multi-domain nature of the material tends to nullify the properties of interest and complicates the thorough understanding of the mechanisms that are responsible for those properties. Here we report the realization of a BiFeO3 material in thin film form with single-domain behaviour in both its magnetism and ferroelectricity: the entire film shows its antiferromagnetic axis aligned along the crystallographic b axis and its ferroelectric polarization along the c axis. With this we are able to reveal that the canted ferromagnetic moment due to the Dzyaloshinskii-Moriya interaction is parallel to the a axis. Furthermore, by fabricating a Co/BiFeO3 heterostructure, we demonstrate that the ferromagnetic moment of the Co film does couple directly to the canted moment of BiFeO3.
Background: Acupuncture has been used for many breast cancer treatment-related problems, but how long the effect lasts is unknown. This meta-analysis aims to evaluate how long the effect of ...acupuncture on breast cancer-related hot flushes and menopause symptoms lasts.
Methods: The research design followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, without language restrictions. Seven databases from inception through February 2019 were accessed; only randomized clinical trials (RCTs) that examined the maintenance effect of acupuncture on hot flushes or menopause symptoms after treatment were included. Cochrane criteria were followed and RevMan 5.2 software was used to analyze trials.
Results: In total, 943 patients from 13 RCTs were analyzed. The meta-analysis showed that acupuncture had no significant long-term maintenance effect on the frequency or severity of hot flushes (p = 0.29; p = 0.34), but had a significant 3-month maintenance effect of ameliorating menopause symptoms at 3 months after treatment ended (p = 0.001). No adverse events were reported.
Conclusions: Acupuncture significantly alleviated menopause symptoms for at least 3 months, but not hot flushes. Breast cancer patients concerned about the adverse effects of hormone therapy could consider acupuncture as an alternative. Additional acupuncture at 3 months after the initial treatment course could be considered. A large-scale study may help to define the optimal guideline for this issue.
Background
Vitamin D has antineoplastic effects, but the synthesis of vitamin D requires ultraviolet radiation, a known risk factor for melanoma.
Objective
To investigate the correlations between ...serum vitamin D levels and risk and prognosis of melanoma.
Methods
A systematic review and meta‐analysis were conducted. Online databases were searched on 31 Oct 2018.
Results
Twenty‐five studies with a total of 11166 patients with melanoma were included. There was no significant difference in serum vitamin D levels between patients with melanoma and controls standardized mean difference (SMD), −0.185; 95% confidence interval (CI), −0.533 to 0.162. However, the prevalence of vitamin D deficiency was significantly higher in patients with melanoma than that in controls (odds ratio, 2.115; 95% CI, 1.151–3.885). In terms of prognosis, serum vitamin D levels were significantly higher in melanoma patients with lower Breslow thickness (≦1 vs. >1 mm: SMD, 0.243; 95% CI, 0.160–0.327). Moreover, melanoma patients with lower vitamin D levels had a significantly higher mortality rate (hazard ratio, 1.558; 95% CI, 1.258–1.931).
Conclusions
Vitamin D deficiency is associated with higher Breslow thickness and mortality in melanoma patients.
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