The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies ...targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.
Summary
The occurrence of osteoporosis in tuberculosis, a chronic infection, has rarely been evaluated. In this study, we found significantly higher incidence rates of osteoporosis (Adjusted hazard ...ratio (AHR) 1.82) and osteoporotic fracture (AHR 2.33) in tuberculosis patients than matched cohorts, which suggest that osteoporosis screening should be considered in tuberculosis patients’ follow-up program. The aim of this study is to determine the occurrence of incident osteoporosis in patients who completed anti-tuberculosis (TB) treatment.
Introduction
Chronic inflammatory disorders are associated with an increased risk of osteoporosis. Although TB is an infectious disease characterized by systemic inflammatory responses, the impact of active TB on incident osteoporosis is unclear. We used the Taiwan National Health Insurance Research Database to investigate the association between history of active TB and incident osteoporosis and osteoporotic fracture.
Methods
In this nationwide retrospective cohort study, active TB patients and their age- and sex-matched controls were identified from the National Health Insurance Research Database in Taiwan during 2000–2012. The occurrence of incident osteoporosis, osteoporotic fractures, and risk factors associated with osteoporosis among TB patients and matched controls were analyzed.
Results
We observed incident osteoporosis in 2.2% (
n
= 86) of the TB patients and in 1.1% (
n
= 162) of the matched controls. The incidence rate of osteoporosis was 4.31 and 1.80 per 1000 person-years, which was significantly higher in TB patients (
p
< 0.001). In multivariate analysis, TB was an independent risk factor for osteoporosis. The other independent factors associated with osteoporosis were older age, female sex, chronic obstructive pulmonary disease, asthma, and lower income. Moreover, we demonstrated that the occurrence of osteoporotic fracture was significantly higher in TB patients.
Conclusions
Patients with a history of active TB have a higher incidence rate of osteoporosis and osteoporotic fracture.
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.
Accurate determination of stellar atmospheric parameters and elemental abundances is crucial for Galactic archaeology via large-scale spectroscopic surveys. In this paper, we estimate stellar ...atmospheric parameters -- effective temperature T sub( eff), surface gravity log g and metallicity Fe/H, absolute magnitudes M sub( V) and M sub( Ks), ...-element to metal (and iron) abundance ratio .../M (and .../Fe), as well as carbon and nitrogen abundances C/H and N/H from the Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) spectra with a multivariate regression method based on kernel-based principal component analysis, using stars in common with other surveys (Hipparcos, Kepler, Apache Point Observatory Galactic Evolution Experiment) as training data sets. Both internal and external examinations indicate that given a spectral signal-to-noise ratio (SNR) better than 50, our method is capable of delivering stellar parameters with a precision of ~100 K for T sub( eff), ~0.1 dex for log g, 0.3-0.4 mag for M sub( V) and M sub( Ks), 0.1 dex for Fe/H, C/H and N/H, and better than 0.05 dex for .../M (.../Fe). The results are satisfactory even for a spectral SNR of 20. The work presents first determinations of C/H and N/H abundances from a vast data set of LAMOST, and, to our knowledge, the first reported implementation of absolute magnitude estimation directly based on a vast data set of observed spectra. The derived stellar parameters for millions of stars from the LAMOST surveys will be publicly available in the form of value-added catalogues. (ProQuest: ... denotes formulae/symbols omitted.)
The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific ...region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study’s objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000–2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre–post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients’ understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.
We describe a novel surgical technique in 31 women with histopathologically confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using a prophylactic infrarenal ...abdominal aortic cross‐clamping technique during caesarean hysterectomy. We conclude that this new surgical procedure is a relatively safe technique to potentially control operative blood loss. Our work may stimulate others to develop protocols assessing this innovative technique to improve the surgical outcome of PAS disorders.
Biodegradable metals have attracted considerable attentions in recent years. Besides the early launched biodegradable Mg and Fe metals, Zn, an essential element with osteogenic potential of human ...body, is regarded and studied as a new kind of potential biodegradable metal quite recently. Unfortunately, pure Zn is soft, brittle and has low mechanical strength in the practice, which needs further improvement in order to meet the clinical requirements. On the other hand, the widely used industrial Zn-based alloys usually contain biotoxic elements (for instance, ZA series contain toxic Al elements up to 40 wt.%), which subsequently bring up biosafety concerns. In the present work, novel Zn-1X binary alloys, with the addition of nutrition elements Mg, Ca and Sr were designed (cast, rolled and extruded Zn-1Mg, Zn-1Ca and Zn-1Sr). Their microstructure and mechanical property, degradation and in vitro and in vivo biocompatibility were studied systematically. The results demonstrated that the Zn-1X (Mg, Ca and Sr) alloys have profoundly modified the mechanical properties and biocompatibility of pure Zn. Zn-1X (Mg, Ca and Sr) alloys showed great potential for use in a new generation of biodegradable implants, opening up a new avenue in the area of biodegradable metals.
Micro-structural evolution and grain refinement in ANSI 304 stainless steel subjected to multiple laser shock processing (LSP) impacts were investigated by means of cross-sectional optical microscopy ...and transmission electron microscopy observations. The plastic strain-induced grain refinement mechanism of the face-centered cubic (fcc) materials with very low stacking fault energy was identified. The micro-structure was obviously refined due to the ultra-high plastic strain induced by multiple LSP impacts. The minimum grain size in the top surface was about 50–200
nm. Multidirectional mechanical twin matrix (MT)–MT intersections led to grain subdivision at the top surface during multiple LSP impacts. Furthermore, a novel structure with submicron triangular blocks was found at the top surface subjected to three LSP impacts. The grain refinement process along the depth direction after multiple LSP impacts can be described as follows: (i) formation of planar dislocation arrays (PDAs) and stacking faults along multiple directions due to the pile up of dislocation lines; (ii) formation of submicron triangular blocks (or irregularly shaped blocks) by the intersection of MT–MT (or MT–PDA or PDA–PDA) along multiple directions; (iii) transformation of MTs into subgrain boundaries; (iv) evolution by continuous dynamic recrystallization of subgrain boundaries to refined grain boundaries. The experimental results and analyses indicate that a high strain with an ultra-high strain rate play a crucial role in the grain refinement process of fcc materials subjected to multiple LSP impacts.
Petrological evidence is provided for anatexis of ultrahigh‐pressure (UHP) metamorphic quartzite in the Sulu orogen. Some feldspar grains exhibit elongated, highly cuspate shapes or occur as ...interstitial, cuspate phases constituting interconnected networks along grain boundaries. Elongated veinlets composed of plagioclase + quartz ± K‐feldspar also occur in grain boundaries. These features provide compelling evidence for anatexis of the UHP quartzite. Zircon grains from impure quartzite are all metamorphic growth with highly irregular shape. They contain inclusions of coesite, jadeite, rutile and lower pressure minerals, including multiphase solid inclusions that are composed of two or more phases of muscovite, quartz, K‐feldspar and plagioclase. All zircon grains exhibit steep REE patterns, similar U–Pb ages and Hf isotope compositions with a weighted mean of 218 ± 2 Ma. Most grains have similar δ18O values of −0.6 to 0.1‰, but a few fall in the range −5.2 to −4.3‰. Thus, these grains would have grown from anatectic melts at various pressures. Zircon O isotope differences indicate that anatectic melts were derived from different sources with contrasting O isotopes, but similar Hf isotopes, that is, one from the quartzite itself and the other probably from the country‐rock granitic gneiss. Zircon grains from pure quartzite contain relict magmatic cores and significant metamorphic overgrowths. Domains that contain eclogite facies minerals exhibit flat HREE patterns, no Eu anomalies and concordant U–Pb ages of c. 220 Ma. Similar U–Pb ages are also obtained for domains that contain lower pressure minerals and exhibit steep REE patterns and marked negative Eu anomalies. These observations indicate that zircon records subsolidus overgrowth at eclogite facies conditions but suprasolidus growth at lower pressures. Zircon enclosed by garnet gave consistent U–Pb ages of c. 214 Ma. Such garnet is interpreted as a peritectic product of the anatectic reaction that involves felsic minerals and possibly amphibole and titanite. The REE patterns of epidote and titanite also record multistage growth and metasomatism by anatectic melts. Therefore, the anatexis of UHP metamorphic rocks is evident during continental collision in the Triassic.
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