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- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Betts, Marissa, J., et al.
(author)
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Early Cambrian chronostratigraphy and geochronology of South Australia
- 2018
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In: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 185, s. 498-543
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Journal article (peer-reviewed)abstract
- The most successful chronostratigraphic correlation methods enlist multiple proxies such as biostratigraphy and chemostratigraphy to constrain the timing of globally important bio- and geo-events. Here we present the first regional, high-resolution shelly fossil biostratigraphy integrated with δ13C chemostratigraphy (and corresponding δ18O data) from the traditional lower Cambrian (Terreneuvian and provisional Cambrian Series 2) of South Australia. The global ZHUCE, SHICE, positive excursions II and III and the CARE are captured in lower Cambrian successions from the Arrowie and Stansbury basins. The South Australian shelly fossil biostratigraphy has a consistent relationship with the δ13C results, bolstering interpretation, identification and correlation of the excursions. Positive excursion II straddles the boundary between the Kulparina rostrata and Micrina etheridgei zones, and the CARE straddles the boundary between the M. etheridgei and Dailyatia odyssei zones, peaking in the lower parts of the latter zone. New CA-TIMS zircon dates from the upper Hawker Group and Billy Creek Formation provide geochronologic calibration points for the upper D. odyssei Zone and corresponding chemostratigraphic curve, embedding the lower Cambrian successions from South Australia into a global chronostratigraphic context. This multi-proxy investigation demonstrates the power of integrated methods for developing regional biostratigraphic schemes and facilitating robust global correlation of lower Cambrian successions from South Australia (part of East Gondwana) with coeval terranes on other Cambrian palaeocontinents, including South and North China, Siberia, Laurentia, Avalonia and West Gondwana.
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| 3. |
- Høland, Maren, et al.
(author)
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Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53
- 2018
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In: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 31:11, s. 1694-1707
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Journal article (peer-reviewed)abstract
- Malignant peripheral nerve sheath tumor is a rare and aggressive disease with poor treatment response, mainly affecting adolescents and young adults. Few molecular biomarkers are used in the management of this cancer type, and although TP53 is one of few recurrently mutated genes in malignant peripheral nerve sheath tumor, the mutation prevalence and the corresponding clinical value of the TP53 network remains unsettled. We present a multi-level molecular study focused on aberrations in the TP53 network in relation to patient outcome in a series of malignant peripheral nerve sheath tumors from 100 patients and 38 neurofibromas, including TP53 sequencing, high-resolution copy number analyses of TP53 and MDM2, and gene expression profiling. Point mutations in TP53 were accompanied by loss of heterozygosity, resulting in complete loss of protein function in 8.2% of the malignant peripheral nerve sheath tumors. Another 5.5% had MDM2 amplification. TP53 mutation and MDM2 amplification were mutually exclusive and patients with either type of aberration in their tumor had a worse prognosis, compared to those without (hazard ratio for 5-year disease-specific survival 3.5, 95% confidence interval 1.78–6.98). Both aberrations had similar consequences on the gene expression level, as analyzed by a TP53-associated gene signature, a property also shared with the copy number aberrations and/or loss of heterozygosity at the TP53 locus, suggesting a common “TP53-mutated phenotype” in as many as 60% of the tumors. This was a poor prognostic phenotype (hazard ratio = 4.1, confidence interval:1.7–9.8), thus revealing a TP53-non-aberrant patient subgroup with a favorable outcome. The frequency of the “TP53-mutated phenotype” warrants explorative studies of stratified treatment strategies in malignant peripheral nerve sheath tumor.
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