SENTIREC - The sentinel node mapping in women with cervical cancer study:Patient-reported early lymphedema and its impact on quality of life

Objective:  To evaluate patient-reported incidence and severity of early lymphedema and its impact on quality of life (QoL) after sentinel lymph node (SLN) mapping only and after SLN and pelvic lymphadenectomy (PL) in women undergoing surgery for early-stage cervical cancer. Methods:  In a national prospective multicenter study, we included women with early-stage cervical cancer from March 2017-January 2021 to undergo radical surgery including SLN mapping. Women with tumors >20 mm underwent completion PL. The incidence and severity of early lymphedema and its influence on QoL were evaluated using validated patient-reported outcome measures before surgery and three months postoperative. We investigated changes over time using linear regression. Results:  Two hundred of 245 (81.6%) included women completed questionnaires at baseline and three months postoperatively. The incidence of early lymphedema was 5.6% (95% CI 2.1-11.8%) and 32.3% (95% CI 22.9-42.7%) in women who underwent SLN mapping only and SLN + PL, respectively. Lymphedema symptoms in the legs, genitals, and groins increased in both groups postoperatively but three times more in women who underwent PL. Lymphedema symptoms after SLN + PL significantly impaired physical performance (p = 0.001) and appearance (p = 0.007). Reporting lymphedema was significantly associated with impaired body image, physical-, role-, and social functioning, and a high level of fatigue. Conclusions:  SLN mapping alone carries a low risk of lymphedema in women undergoing surgery for early-stage cervical cancer. In contrast, completion PL is associated with a high incidence of early lymphedema. Reporting lymphedema is associated with significant impairment of several physical, psychological, and social aspects of QoL

Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified?

BACKGROUND: A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged by the severity of induced disease, which in some cases necessitated humane euthanasia. A pilot study was therefore performed in order to establish the sufficient inoculum concentration and application protocol needed to produce signs of liver dysfunction within limits of our pre-defined humane endpoints. METHODS: Four pigs received 1 × 10(8) cfu/kg BW of S. aureus, and two controls were sham inoculated with saline. A fixed infusion rate of 3 mL/min was used, while the inoculum concentration, i.e., the dose volume, was changed between the pigs. The following dose volumes were used: 10 mL (n = 1), 20 mL (n = 2), and 30 mL (n = 1), corresponding to infusion durations of 3.33, 6.66, and 10 min at dose rates of 3 × 10(7), 1.5 × 10(7), and 1 × 10(7) cfu/min/kg BW, respectively. Blood samples were drawn for complete blood count, clinical chemistry, and inflammatory markers before and every 6 h after inoculation. Prior to euthanasia, a galactose elimination capacity test was performed to assess liver function. Pigs were euthanised 48 h post inoculation for necropsy and histopathological evaluation. RESULTS: While infusion times of 6.66 min, and higher, did not induce liver dysfunction (n = 3), the infusion time of 3.33 min (n = 1) caused alterations in parameters similar to what had been seen in our previous studies, i.e., increasing bilirubin and aspartate aminotransferase, as well as histopathological occurrence of intravascular fibrin split products in the liver. This pig was however euthanised after 30 h, according to humane endpoints. CONCLUSIONS: A usable balance between scientific purpose and animal welfare could not be achieved, and we therefore find it hard to justify further use of this conscious porcine sepsis model. In order to make a model of translational relevance for human sepsis, we suggest that future model versions should use long-term anaesthesia

Scald resistance in hybrid rye (Secale cereale): genomic prediction and GWAS

Rye (Secale cereale L.) is an important cereal crop used for food, beverages, and feed, especially in North-Eastern Europe. While rye is generally more tolerant to biotic and abiotic stresses than other cereals, it still can be infected by several diseases, including scald caused by Rhynchosporium secalis. The aims of this study were to investigate the genetic architecture of scald resistance, to identify genetic markers associated with scald resistance, which could be used in breeding of hybrid rye and to develop a model for genomic prediction for scald resistance. Four datasets with records of scald resistance on a population of 251 hybrid winter rye lines grown in 2 years and at 3 locations were used for this study. Four genomic models were used to obtain variance components and heritabilities of scald resistance. All genomic models included additive genetic effects of the parental components of the hybrids and three of the models included additive-by-additive epistasis and/or dominance effects. All models showed moderate to high broad sense heritabilities in the range of 0.31 (SE 0.05) to 0.76 (0.02). The model without non-additive genetic effects and the model with dominance effects had moderate narrow sense heritabilities ranging from 0.24 (0.06) to 0.55 (0.08). None of the models detected significant non-additive genomic variances, likely due to a limited data size. A genome wide association study was conducted to identify markers associated with scald resistance in hybrid winter rye. In three datasets, the study identified a total of twelve markers as being significantly associated with scald resistance. Only one marker was associated with a major quantitative trait locus (QTL) influencing scald resistance. This marker explained 11-12% of the phenotypic variance in two locations. Evidence of genotype-by-environment interactions was found for scald resistance between one location and the other two locations, which suggested that scald resistance was influenced by different QTLs in different environments. Based on the results of the genomic prediction models and GWAS, scald resistance seems to be a quantitative trait controlled by many minor QTL and one major QTL, and to be influenced by genotype-by-environment interactions