| 1. |
- Teede, Helena J, et al.
(författare)
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Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.
- 2023
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Ingår i: Fertility and sterility. - 1556-5653. ; 120:4, s. 767-793
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Tidskriftsartikel (refereegranskat)abstract
- What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist.The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout.This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC).The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program.This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
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| 2. |
- Naeser, Ylva, et al.
(författare)
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Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study
- 2023
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population.Methods: This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses.Findings: The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients.Interpretation: Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS.
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| 3. |
- Decker, Ralph, 1968, et al.
(författare)
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Case report of a girl with secondary amenorrhea associated with aurantiasis cutis
- 2016
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: --- Aurantiasis cutis is a condition of yellowish or golden skin discoloration that can result from eating excessive amounts of foods containing carotene leading to hypercarotenemia(1), described causing secondary amenorrhea(2). Objective & hypothesis: --- Hypercarotenemia can cause secondary amenorrhea without overconsumption of excessive quantities of carotene. Results: --- Laboratory tests showed a ß-Carotene level more than the 2-fold above the upper reference level. Hyperbilirubinemia could be excluded. Hypogonadotropic hypogonadism was not present. There was no evidence for adrenal dysfunction. Liver function tests were normal. Material/ Methods: --- A 16-year-old girl presented to our endocrine outpatient clinic with a 2-year history of varying yellow discoloration of her skin and secondary amenorrhea. The findings of the general physical examination were normal, but there was a marked yellow discoloration of the palms, soles, and nasolabial folds. A dietary history revealed a low carotene diet, but also a low carbohydrate diet. BMI was 19.9 kg/m² (-0.2 SDS) without signs of anorexia. Discussion: --- In this girl we observed hypercarotenemia associated with secondary nonhypothalamic amenorrhea in absence of excess external intake of carotenes. This suggests an intrinsic reason due to a polymorphism(3) in ß-carotene 15,15'-monooxygenase (BCO)(4), an enzyme breaking down carotenes to vitamin A(5). Phenotype-genotype association studies are needed to confirm this hypothesis. Conclusion: --- Secondary non-hypothalamic amenorrhea can be associated with hypercarotenemia. References: --- 1. Tanikawa K, Seta K, Machii A, Itoh S 1961 [Aurantiasis cutis due to overeating of dried laver (nori): a case report]. Jpn J Med Sci Biol 50:414-419 2. Kemmann E, Pasquale SA, Skaf R 1983 Amenorrhea associated with carotenemia. JAMA 249:926-929 3. Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G 2009 Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB j 23:1041-1053 4. Frumar AM, Meldrum DR, Judd HL 1979 Hypercarotenemia in hypothalamic amenorrhea. Fertil Steril 32:261-264 5. Lindqvist A, Andersson S 2002 Biochemical properties of purified recombinant human beta-carotene 15,15'-monooxygenase. J Biol Chem 277:23942-23948
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| 4. |
- Walser, Marion, 1961, et al.
(författare)
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Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats.
- 2011
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1532-2238. ; 21:1, s. 16-24
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) therapy substantially improves several cognitive functions in hypopituitary experimental animals and in humans. Although a number of biochemical correlates to these effects have been characterized, there are no comprehensive analysis available examining effects of GH on the brain. Hypophysectomized female rats were given replacement therapy with cortisol and thyroxine (=hx). Subcutaneous infusions of bovine GH (bGH, henceforth designated GH) were supplied in osmotic minipumps for 6 days (=hx+GH). To evaluate whether GH normalized specific transcript expression levels in cerebral cortex, pituitary-intact rats were used as normal controls. DNA microarrays (Affymetrix) of cerebrocortical samples showed that 24 transcripts were changed by more than 1.5-fold by GH treatment in addition to being normalized by GH treatment. The expression of three selected highly regulated transcripts was confirmed by quantitative real-time polymerase chain reaction analysis. These were the GABAB receptor 1, Lissencephaly-1 protein (LIS-1), and hemoglobin b or beta-globin. A similar regulation was found for hemoglobin b also in the hippocampus. Both the GABAB receptor 1 and hemoglobin b may have importance for the previously described neuroprotective and perhaps cognitive potential of GH treatment. Altogether, these results show that short term GH treatment affects a number of transcripts in cerebral cortex with various biological functions. These transcripts represent potential novel mechanisms by which GH can interact with the brain.
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| 5. |
- Arabpour, Mohammad, et al.
(författare)
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ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection
- 2022
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 15:4, s. 745-761
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Tidskriftsartikel (refereegranskat)abstract
- Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103(+) cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3-/- mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt(+) T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
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| 6. |
- Dahl, Anna K., et al.
(författare)
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Agreement between self-reported and measured height, weight and body mass index in old age : a longitudinal study with 20 years of follow-up
- 2010
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 39:4, s. 445-451
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Tidskriftsartikel (refereegranskat)abstract
- Background: self-reported body mass index (BMI) based on self-reported height and weight is a widely used measure of adiposity in epidemiological research. Knowledge about the accuracy of these measures in late life is scarce.Objective: the study aimed to evaluate the accuracy and changes in accuracy of self-reported height, weight and BMI calculated from self-reported height and weight in late life.Design: a longitudinal population-based study with five times of follow-up was conducted.Participants: seven hundred seventy-four community-living men and women, aged 40–88 at baseline (mean age 63.9), included in The Swedish Adoption/Twin Study of Aging.Methods: participants self-reported their height and weight in a questionnaire, and height and weight were measured by experienced research nurses at an in-person testing five times during a 20-year period. BMI was calculated as weight (kilogramme)/height (metre)2.Results: latent growth curve modelling showed an increase in the mean difference between self-reported and measured values over time for height (0.038 cm/year) and BMI (0.016 kg/m2/year), but not for weight.Conclusions: there is a very small increase in the mean difference between self-reported and measured BMI with ageing, which probably would not affect the results when self-reported BMI is used as a continuous variable in longitudinal studies.
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| 7. |
- Florén, Claes-Henrik, et al.
(författare)
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Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine
- 1998
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Ingår i: Journal of Internal Medicine. - 1365-2796. ; 243:2, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone. DESIGN: Retrospective study. SETTING: University Hospital of Malmo, Sweden. SUBJECTS: A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease. METHODS: Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2-L4. RESULTS: Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P = 0.011) lower Z-score of L2-L4 (-0.87 +/- 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 +/- 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density. CONCLUSIONS: Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.
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| 8. |
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| 9. |
- Kjölhede, P., et al.
(författare)
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Individualized treatment for ovarian cancer may become possible
- 2015
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Ingår i: Läkartidningen. - 0023-7205. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered.
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| 10. |
- Nordahl, Emma, et al.
(författare)
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Domain 5 of high molecular weight kininogen is antibacterial.
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:41, s. 34832-34839
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides are important effectors of the innate immune system. These peptides belong to a multifunctional group of molecules that apart from their antibacterial activities also interact with mammalian cells and glycosaminoglycans and control chemotaxis, apoptosis, and angiogenesis. Here we demonstrate a novel antimicrobial activity of the heparin-binding and cell-binding domain 5 of high molecular weight kininogen. Antimicrobial epitopes of domain 5 were characterized by analysis of overlapping peptides. A peptide, HKH20 (His(479) - His(498)), efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and the Gram-positive Enterococcus faecalis. Fluorescence microscopy and electron microscopy demonstrated that HKH20 binds to and induces breaks in bacterial membranes. Furthermore, no discernible hemolysis or membrane-permeabilizing effects on eukaryotic cells were noted. Proteolytic degradation of high molecular weight kininogen by neutrophil-derived proteases as well as the metalloproteinase elastase from P. aeruginosa yielded fragments comprising HKH20 epitopes, indicating that kininogen-derived antibacterial peptides are released during proteolysis.
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