Breast Milk Dioxins in Hong Kong and Pearl River Delta

There are no previous reports from South China on chemically determined polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like poly-chlorinated biphenyls (PCBs) in human breast milk expressed as World Health Organization (WHO) toxic equivalents (TEQs). In a 2002–2003 WHO exposure study, 13 pools of breast milk comprising samples from 316 primiparous women in Hong Kong in 2002 were analyzed by gas chromatography/mass spectrometry for 29 PCDD/F and dioxin-like PCB congeners. Total WHO-TEQs ranged from 8.97 to 16.7 pg/g fat (weighted mean, 12.9 pg; weighted median, 13.4 pg). Variations in TEQs included positive associations with age (R(2) = 0.73, p < 0.0005), higher consumption of dairy products and seafood, and lower TEQs in overseas mothers and ever-smokers. Congener profiles indicated geographic specificity of exposure in Hong Kong, mainland China, and overseas Asian countries, including higher proportions of PCB-TEQs (overseas) and PCDF-TEQs (mainland China). The median TEQs of PCDD/Fs (8.69 pg/g fat) and PCBs (4.73 pg/g fat) in Hong Kong were highest among the five Asian Pacific countries but lower than the levels for at least half of the European countries that participated in the WHO study. However, future international studies should incorporate mother’s age in the design of the pooling strategy to allow standardization by other exposure factors and valid comparisons among different countries. The findings allow support for the WHO breast-feeding advisory. Trends in human dioxin levels in the region cannot yet be determined, and rigorous controls are needed to reduce emissions of dioxins and human exposure in mainland China

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Degradation of haloaromatic compounds

An ever increasing number of halogenated organic compounds has been produced by industry in the last few decades. These compounds are employed as biocides, for synthetic polymers, as solvents, and as synthetic intermediates. Production figures are often incomplete, and total production has frequently to be extrapolated from estimates for individual countries. Compounds of this type as a rule are highly persistent against biodegradation and belong, as "recalcitrant" chemicals, to the class of so-called xenobiotics. This term is used to characterise chemical substances which have no or limited structural analogy to natural compounds for which degradation pathways have evolved over billions of years. Xenobiotics frequently have some common features. e.g. high octanol/water partitioning coefficients and low water solubility which makes for a high accumulation ratio in the biosphere (bioaccumulation potential). Recalcitrant compounds therefore are found accumulated in mammals, especially in fat tissue, animal milk supplies and also in human milk. Highly sophisticated analytical techniques have been developed for the detection of organochlorines at the trace and ultratrace level

Obstetric performance of elderly primiparae.

link_to_subscribed_fulltex

Next-Generation Sequencing with a 54-Gene Panel Identifies Unique Mutational Profile and Prognostic Markers in Chinese Patients with Myelofibrosis

634. Myeloproliferative Syndromes: Clinical: Poster I: no. 1638Introduction and objectives: Myelofibrosis (MF) has the worst outcome amongst various myeloproliferative neoplasms. Its prognosis is determined by clinicopathologic features and mutations in key driver genes. An increasing number of gene mutations involving various biological pathways in myeloid malignancies has been discovered. The prognostic significance of these mutations have not been clearly defined. In this study, we aim to describe the genomic characteristic in a large cohort of MF patients and identify clinical and molecular predictors of outcome. Methods: We evaluated the genetic profile of 101 patients with MF (primary, N=70; secondary, N=30) using next-generation sequencing with a 54-gene panel comprising: ABL1, ASXL1, ATRX, BCOR, BCORL1, BRAF, CALR, CBL, CBLB, CBLC, CDKN2A, CEBPA, CSF3R, CUX1, DNMT3A, ETV6, EZH2, FBXW7, FLT3, GATA1, GATA2, GNAS, HRAS, IDH1, IDH2, IKZF1, JAK2, JAK3, KDM6A, KIT, KMT2A, KRAS, MPL, MYD88, NOTCH1, NPM1, NRAS, PDGFRA, PHF6, PTEN, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC1A, SMC3, SRSF2, STAG2, TET2, TP53, U2AF1, WT1, ZRSR2. Multivariate cox regression analysis was used to determine prognostic factors for overall survival (OS) and leukemia-free survival (LFS). Results: We identified mutations in 39 genes implicated in myeloid malignancies (Figure 1A). 96 patients (95%) with MF had a mutation in 1 or more genes: 14 patients (13.9%) had 1 mutation, 38 patients (37.6%) had 2 mutations, 18 patients (17.8%) had 3 mutations, 15 patients (14.9%) had 4 mutations, 7 patients (6.9%) had 5 mutations and 4 patients (4%) had 6 or more mutations. TET2/JAK2V617F (16 patients, 15.9%), ASXL1/JAK2V617F (12 patients, 11.9%) and ASXL1/CALR (10 patients, 9.9%) were the most frequently co-mutated genes (Figure 1B). Other JAK2 variants occurred concomitantly with JAK2V617F in 10 patients (9.9%) and CALR mutations in 4 patients (4%) mutations. Other frequently concomitant mutations included CUX1/JAK2V617F (6 patients, 5.9%), EZH2/JAK2V617F (6 patients, 5.9%), RUNX1/JAK2V617F (5 patients, 5%), SF3B1/JAK2V617F (5 patients, 5%), SETBP1/JAK2V617F (4 patients, 4%) and ZRSR2/JAK2V617F (4 patients, 4%). The median follow-up of the cohort was 49 (1-256) months. The 5-year and 10-year OS were 66.3% and 35.4%. The 5-year and 10-year LFS of were 84% and 63.3%. There were no statistically significant differences in OS and LFS between primary and secondary MF. Significant negative prognostic indicators were identified on multivariate analysis, including male gender (P=0.044), age > 65 years (P=0.044), Hb < 10g/dL (P=0.001), mutated CUX1 (P=0.003) and mutated TP53 (P=0.043) for OS, and Hb < 10g/dL (P=0.007), mutated TP53 (P=0.043) and mutated IDH2 (P=0.001) for LFS. In primary MF, inferior prognostic indicators included male gender (P=0.031), Hb < 10g/dL (P=0.002), platelet count < 100 x 109/L (P=0.021), mutated TET2 (P=0.011) and mutated CUX1 (P=0.011) for OS; and Hb < 10g/dL (P=0.027), mutated RUNX1 (P=0.019) and mutated DNMT3A (P=0.004) for LFS. In JAK2V617F positive MF, inferior prognostic indicators included mutated ASXL1 (P=0.006) and mutated SRSF2 (P<0.001) for OS; and mutated U2AF1 (P=0.037) for LFS. Conclusion: Our study demonstrated unique molecular profiles and prognostic predictors of outcome in Chinese patients with MF