| 1. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 2. |
- Batchelor, Timothy J. P., et al.
(författare)
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Guidelines for enhanced recovery after lung surgery : recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS)
- 2019
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Springer. - 1010-7940 .- 1873-734X. ; 55:1, s. 91-115
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Forskningsöversikt (refereegranskat)abstract
- Enhanced recovery after surgery is well established in specialties such as colorectal surgery. It is achieved through the introduction of multiple evidence-based perioperative measures that aim to diminish postoperative organ dysfunction while facilitating recovery. This review aims to present consensus recommendations for the optimal perioperative management of patients undergoing thoracic surgery (principally lung resection). A systematic review of meta-analyses, randomized controlled trials, large non-randomized studies and reviews was conducted for each protocol element. Smaller prospective and retrospective cohort studies were considered only when higher-level evidence was unavailable. The quality of the evidence base was graded by the authors and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery after Surgery Society and the European Society for Thoracic Surgery. Recommendations were developed for a total of 45 enhanced recovery items covering topics related to preadmission, admission, intraoperative care and postoperative care. Most are based on good-quality studies. In some instances, good-quality data were not available, and subsequent recommendations are generic or based on data extrapolated from other specialties. In other cases, no recommendation can currently be made because either equipoise exists or there is a lack of available evidence. Recommendations are based not only on the quality of the evidence but also on the balance between desirable and undesirable effects. Key recommendations include preoperative counselling, nutritional screening, smoking cessation, prehabilitation for high-risk patients, avoidance of fasting, carbohydrate loading, avoidance of preoperative sedatives, venous thromboembolism prophylaxis, prevention of hypothermia, short-acting anaesthetics to facilitate early emergence, regional anaesthesia, nausea and vomiting control, opioid-sparing analgesia, euvolemic fluid management, minimally invasive surgery, early chest drain removal, avoidance of urinary catheters and early mobilization after surgery. These guidelines outline recommendations for the perioperative management of patients undergoing lung surgery based on the best available evidence. As the recommendation grade for most of the elements is strong, the use of a systematic perioperative care pathway has the potential to improve outcomes after surgery.
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| 3. |
- Soletormos, Gyorgy, et al.
(författare)
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Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer Updated Guidelines From the European Group on Tumor Markers
- 2016
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 26:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial varian cancer. Methods: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. Results: Because of its low sensitivity (50-62% for early stage epithelial ovarian cancer) and limited specificity (94-98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery. Conclusions: At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.
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