Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Study of the protective role of ginseng aqueous extract on Lipid profile (TC), (Tg), (HDL) and (LDL) in male rabbits treated with lead acetate for 30 days

The Study involved twenty healthy adult white male rabbits (Lepus arcticus L.). the average weight (1500- 1600) Kg and aged from eight months to one year. The rabbits ware divided to four groups(G) each group contains five rabbits. G1 was treated with normal saline (1.5) ml orally as negative control group, G2 was treated with lead acetate (150) mg/kg as positive control group, G3 was treated with the aqueous extract of the Panax ginseng&nbsp; (400 ) mg/kg b.wt&nbsp; and G4&nbsp; was&nbsp; treated with the aqueous extract of the Panax ginseng ( 400) mg/kg b.wt&nbsp; after 3 hours given them lead acetate (150 mg/kg b. wt/day) for peroid 30 days . study aimed to determine the protective role of Panax ginseng extract on Lipid profile like total cholesterol (TC) , triglycerides (Tg) , high-density lipoproteins (HDL) , low-density lipoproteins(LDL). The result of&nbsp; present study showed:- increase (P&lt;0.05) in mean levels of high-density lipoproteins (HDL) in the (G3) and (G4) group compare with Second group (positive control G2).&nbsp; decrease (P&lt;0.05) in mean levels total cholesterol (TC), triglycerides (Tg) low-density lipoproteins(LDL) in group (G3) and (G4) compare with Second group (positive control G2)

Study of the protective role of panax ginseng aqueous extract on the antioxidants glutathione (GSH) and oxidants malondialdehyde (MDA) in male rabbits treated with lead acetate for 30 days

The Study involved twenty healthy adult white male rabbits (Lepus arcticus L.). the average weight (1500- 1600) Kg and aged from eight months to one year. The rabbits ware divided to four groups(G) each group contains five rabbits. G1 was treated with normal saline (1.5) ml orally as negative control group, G2 was treated with lead acetate (150) mg/kg as positive control group, G3 was treated with the aqueous extract of the Panax ginseng (400 ) mg/kg b.wt&nbsp; and G4&nbsp; was&nbsp; treated with the aqueous extract of the Panax ginseng ( 400) mg/kg b.wt&nbsp; after 3 hours given them lead acetate (150 mg/kg b. wt/day) for peroid 30 days . study aimed to determine the protective role of Panax ginseng extract on the antioxidants glutathione GSH and oxidants malondialdehyde (MDA) in the blood serum of male rabbits for 30 days. The result of present study showed: increase (P&lt;0.05) in mean levels of glutathione (GSH) in the (G3) and (G4) group compare with Second group (positive control G2). decrease (P&lt;0.05) in mean levels of malondialdehyde (MDA) in group (G3) and (G4) compare with Second group (positive control G2)

Relationship between the Floristic Composition and Soil Characteristics of a Tropical Rainforest (TRF)

Hutan Rimba Alam (HRA), Putrajaya is an urban forest which is the habitat for various tropical rainforest species. A field survey was undertaken to state the floristic composition, investigate the soil characteristics and identify the relationship between the recorded plant communities and soil characteristics. Six plots sized 10 &times; 10 m square were established in a lowland area of which 93 individual trees were identified. Moreover, the floristic composition revealed vascular tree communities consisting of 10 botanical families, 15 genera, and 27 species with Dipterocarpaceae as being predominant. Based on the important value index (IVI), Mangifera odorata (Anacardiaceae) was the highest (IVI = 68.80%). Furthermore, large trees such as Koompassia excelsa (Becc.) Taub. (Fabaceae) and Sandoricum koetjape (Burm.f.) Merr. (Meliaceae), with heights ranging from 17 m to 24 m, indicated that HRA is on the way to becoming a mature forest. The soil pH in all plots showed acidic properties, with a mean pH of 4.69 that is considered normal for tropical rainforests. The pH of the soils in HRA, Putrajaya had a positive correlation with the CEC and with nitrogen, but the value was low; however, the correlation was negative with C and P. The CEC had a relatively low correlation with C, N and P. Carbon had a very high correlation with N but low with P. Meanwhile, nitrogen had a very negatively low correlation with P. Extractable phosphorus exhibited a mean of 2.22 mg/kg which is normally used in plants for fruits, roots, and flower development. The present study revealed that plant communities in the urban forest in Putrajaya, meaning the diversity of the plant species belonging to a wide range of families, were established on acid soil, matching with the overall characteristics of tropical forest soils. With regard to the climate change context, which is leading to many altered ecosystems, the authors expect that the outputs of this research will be valued by decision makers for a better management of the forest

Students' participation in collaborative research should be recognised

Letter to the editor

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine