Paternal HLA-Derived Epitopes and Live Birth in Secondary Recurrent Pregnancy Loss: New Insights From a Clinical Trial

Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%–3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune-related factors may play a role. Previously, a randomised controlled trial using immunoglobulin (IVIG) in sRPL women with a history of four pregnancy losses performed in our RPL unit did not show significant effects of IVIG treatment overall. Yet, some evidence suggests potential benefits for a subset of sRPL patients. In the cohort used for the randomised controlled trial, we examined the role of maternal HLA class II-presented fetal HLA-derived epitopes in sRPL using the predicted indirectly recognisable HLA epitopes (PIRCHE-II) algorithm. In the placebo group, sRPL mothers with an anti-HLA antibody response had higher PIRCHE-II scores when having a live birth compared with sRPL women who experienced another pregnancy loss. This difference was not observed in the IVIG-treated group. Furthermore, as a proxy for T-cell memory, the number of overlapping peptides between the two paternal haplotypes in couples having live births without treatment displayed a larger number of overlapping peptides. This effect was primarily driven by class II-derived peptides. These results suggest that specific combinations of sRPL mothers and fathers, particularly those with an anti-HLA antibody response, may generate higher PIRCHE-II scores, which could contribute to successful live births. Understanding these immune interactions may provide insights for personalised diagnostic and therapeutic strategies in sRPL

Defining and sparing sexual function-related organs at risk for rectal cancer radiotherapy

Background and purpose: Sexual dysfunction is a common consequence of pelvic radiotherapy, influenced by psychological, physical, social, and relational factors. Research has focused on vaginal dose and stenosis in females and penile bulb dose and erectile dysfunction in males, with limited attention to domains, such as arousal, desire, and satisfaction. In the Danish Colorectal Cancer Radiotherapy Group, we aimed to: (1) Develop an atlas of sexual function-related organs at risk and (2) Evaluate if these organs at risk could be spared without compromising target coverage in rectal cancer radiotherapy planning. Patient/material and methods: A multidisciplinary approach was adopted, involving oncology, physics, psychology, surgery, and radiology. MRI-based anatomical definitions were established, and an atlas was created for both males and females, including inferior hypogastric plexus, pudendal vessels/Alcock’s canal, neurovascular bundle, penile bulb, vagina, paracolpium, and bulboclitoris. For comparative planning standard and sexual function-sparing plans were created for each patient. Results: A national consensus atlas for sexual function-related organs at risk was developed. Standard plans (n = 15) and sexual function-sparing plans (n = 15) for seven males and eight females were compared. Sparing of pudendal vessels and bulboclitoris was feasible without compromising the standard plan. For sexual function-related organs at risk in or close to the target, D2% could often be improved. Interpretation: Our consensus-based delineation and planning demonstrate that radiation dose to many sexual function-related organs at risk can be spared or optimized without compromising target coverage or dose to standard organs at risk. Future work includes implementing patient-reported outcomes and integrating these new organs at risk into standard radiotherapy planning.</p

Microplastics; occurrence, levels and implications for environment and human health related to food. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

Report from the Norwegian Scientific Committee for Food Safety (VKM) 2019:16. Microplastics; occurrence, levels and implications for environment and human health related to food. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment. Source at https://www.vkm.no/. The steering committee of VKM has self-initiated a mandate for an opinion on microplastics based on recently published international and/or national reports complemented with literature from December 2016 to February 2019. The mandate requested a summary of the state of knowledge on the presence of microplastics in the environment and the implications for the ecosystem, terrestrial and aquatic organisms, food production and human health. An overview of main national and international ongoing initiatives was also requested, and highlighting of data gaps where specific Norwegian data was needed

Microplastics; occurrence, levels and implications for environment and human health related to food. Scientific opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

publishedVersio

Microplastics; occurrence, levels and implications for environment and human health related to food. Scientific opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

publishedVersio

Microplastics; occurrence, levels and implications for environment and human health related to food. Scientific opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

The steering committee of VKM has self-initiated a mandate for an opinion on microplastics based on recently published international and/or national reports complemented with literature from December 2016 to February 2019. The mandate requested a summary of the state of knowledge on the presence of microplastics in the environment and the implications for the ecosystem, terrestrial and aquatic organisms, food production and human health. An overview of main national and international ongoing initiatives was also requested, and highlighting of data gaps where specific Norwegian data was needed. VKM appointed a working group consisting of two VKM members and eight external experts (two are former VKM-members), in addition to a project leader from the VKM secretariat to write the assessment.publishedVersio

Benefit and risk assessment of fish in the Norwegian diet - Scientific Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

publishedVersio

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Bumpy road: implementing integrated psychiatric and somatic care in joint-specialty emergency departments: a mixed-method study using Normalization Process Theory

PurposeLife expectancy is 15–20 years shorter for individuals with than for people without mental illness. Assuming that undiagnosed and undertreated somatic conditions are significant causes, the Central Denmark Region set out to implement joint psychiatric and somatic emergency departments (EDs) to support integrated psychiatric/somatic care as an effort to prolong the lifetime of individuals with mental illness. Through the lens of Normalization Process Theory, the authors examine healthcare frontline staff’s perceptions of and work with the implementation of integrated psychiatric/somatic care in the first joint-specialty ED in Denmark.Design/methodology/approachA single-case mixed-methods study using Normalization Process Theory (NPT) as an analytic framework to evaluate implementation of psychiatric/somatic integrated care (IC) in a joint-specialty emergency department. Data were generated from observations, qualitative interviews and questionnaires distributed to the frontline staff.FindingsImplementation was characterized by a diffuse normalization leading to an adaption of the IC in a fuzzy alignment with existing practice. Especially, confusion among the staff regarding how somatic examination in the ED would ensure prolonged lifetime for people with mental illness was a barrier to sense-making and development of coherence among the staff. The staff questioned the accuracy of IC in the ED even though they recognized the need for better somatic care for individuals with mental illness.Practical implicationsThis study highlights that a focus on outcomes (prolonging lifetime for people with mental illness and reducing stigmatization) can be counterproductive. Replacing the outcome focus with an output focus, in terms of how to develop and implement psychiatric/somatic IC with the patient perspective at the center, would probably be more productive.Originality/valueIn 2020, the Danish Health Authorities published new whole-system recommendations for emergency medicine (EM) highlighting the need for intensifying integrated intra and interorganizational care including psychiatric/somatic IC (ref). Even though this study is not conclusive, it points to subjects that can help to identify resources needed to implement psychiatric/somatic IC and to pitfalls. The authors argue that the outcome focus, prolonging the lifetime for individuals with mental illness by identifying somatic illness, was counterproductive. In accordance with the recommendations of contemporary implementation studies, the authors recommend a shift in focus from outcome to output focus; how to develop and implement psychiatric/somatic IC.</jats:sec