| 1. |
- Margolin, Sara, et al.
(författare)
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A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.
- 2011
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.
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| 2. |
- Matikas, Alexios, et al.
(författare)
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Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 168:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs. The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up. A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up. In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.
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| 3. |
- Bergh, Jonas, et al.
(författare)
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Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer : A randomised trial
- 2000
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 356:9239, s. 1384-1391
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. Methods: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. Findings: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. Interpretation: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.
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| 4. |
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| 5. |
- Zou, Zhiyuan V., et al.
(författare)
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Antioxidants promote intestinal tumor progression in mice.
- 2021
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Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.
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| 6. |
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| 7. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Prevalence and Duration of PTSD in Survivors Six Years After a Natural Disaster
- 2013
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Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 27:3, s. 347-352
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to examine the prevalence of posttraumatic stress disorder (PTSD) in survivors with low levels of risk factors for PTSD. The sample included 142 adults (58% women, 54% university education, 93% employed/students/retired) on vacation in Southeast Asia during the 2004 Indian Ocean disaster. Semi-structured clinical interviews (SCID-I) were performed after 6 years including PTSD, depression, specific phobia, and alcohol abuse. The 6-year prevalence of PTSD was 11.3% and the current prevalence was 4.2%, with onset mainly within 1 month and remission within 3 years post-disaster. Suicidal ideation and comorbidity were common in PTSD cases. Lifetime prevalence of depression was 19%, specific phobia 7%, and alcohol abuse 4%. The findings suggest elevated levels of PTSD but not other disorders as compared with general population samples, but still lower levels than other disaster samples. Despite benign circumstances, however, the course and burden of PTSD were comparable to similar studies.
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| 8. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Properties of Swedish Posttraumatic Stress Measures after a Disaster
- 2014
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Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 28:4, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the properties of Swedish versions of self-report measures of posttraumatic stress disorder (PTSD), with emphasis on the Impact of Event Scale–Revised (IES-R). Survey data from adult survivors 1, 3, and 6 years after the 2004 Indian Ocean tsunami (n = 1506) included the IES-R (from which the IES-6 was derived) and the 12-item General Health Questionnaire (GHQ-12). The PTSD Checklist (PCL) was included in one survey. A structured clinical interview was performed after 6 years (n = 142). Factor analyses of the IES-R and PCL indicated that a dysphoric-arousal model provided good fit invariant across assessments. Both measures were accurate in excluding PTSD while all measures provided poorer positive predictive values. The IES-R, but not the IES-6 and GHQ-12, evidenced stability across assessments. In conclusion, the Swedish IES-R and PCL are sound measures of chronic PTSD, and the findings illustrate important temporal aspects of PTSD assessment.
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| 9. |
- Attaye, Ilias, et al.
(författare)
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Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes
- 2023
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Ingår i: ISCIENCE. - 2589-0042. ; 26:8
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Tidskriftsartikel (refereegranskat)abstract
- High-protein diets are promoted for individuals with type 2 diabetes (T2D). How-ever, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized -controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and-derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure.
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| 10. |
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| 11. |
- Bergh Johannesson, Kerstin, 1949-, et al.
(författare)
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Impact of Exposure to Trauma on Posttraumatic Stress Disorder Symptomatology in Swedish Tourist Tsunami Survivors
- 2009
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Ingår i: Journal of Nervous and Mental Disease. - 0022-3018 .- 1539-736X. ; 197:5, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to examine long-term mental health and posttraumatic stress symptomatology in a Swedish tourist population after exposure to the 2004 Southeast Asian tsunami. Data from 4822 returned questionnaires 14 months after the disaster were analyzed. Respondents were categorized into 3 subgroups: (1) danger-to-life exposure group (having been caught or chased by the waves), (2) nondanger-to-life exposure group (exposed to other disaster-related stressors), and (3) low exposure group. Main outcome measures were General Health Questionnaire-12 and Impact of Event Scale-22-Revised. Danger-to-life exposure was an important factor in causing more severe posttraumatic stress symptoms and in affecting mental health. Female gender, single status, and former trauma experiences were associated with greater distress. Other factors related to more severe symptoms were loss of relatives, physical injuries, viewing many dead bodies, experiencing life threat, and showing signs of cognitive confusion. Disaster exposure has a substantial impact on survivors, which stresses the need for long-lasting support.
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| 12. |
- Bergh Johannesson, Kerstin, 1949-, et al.
(författare)
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Krisstöd vid allvarlig händelse
- 2017. - 2
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Ingår i: Traumatologi. - : Liber. - 9789147114238
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Prolonged Grief Among Traumatically Bereaved Relatives Exposed and Not Exposed to a Tsunami
- 2011
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 24:4, s. 456-464
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies on the mental health consequences of traumatic exposure to a disaster compare those exposed to those not exposed. Relatively few focus on the effect of the death of a close relative caused by the disaster-suffering a traumatic bereavement. This study compared the impact on 345 participants who lost a close relative in the 2004 Indian Ocean tsunami, but who were themselves not present, to 141 who not only lost a relative, but also were themselves exposed to the tsunami. The focus was on psychological distress assessed during the second year after the sudden bereavement. Findings were that exposure to the tsunami was associated with prolonged grief (B = 3.81) and posttraumatic stress reactions (B 665), and doubled the risk for impaired mental health. Loss of children increased the risk for psychological distress (prolonged grief B = 692; The Impact of Event Scale-Revised: B = 610; General Health Questionnaire-12: OR = 2.34). Women had a higher frequency of prolonged grief For men, loss of children presented a higher risk for prolonged grief in relation to other types of bereavement (B = 636 vs. loss of partner). Further long-term follow-up could deepen the understanding of how recovery after traumatic loss is facilitated.
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| 14. |
- Bergh Johannesson, Kerstin, 1949-, et al.
(författare)
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Psychological Crisis Support in Major Incidents
- 2012
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Ingår i: Medical Responses to Major Incidents and Disasters. - Berlin Heidelberg : Springer London. - 9783642218941 ; , s. 363-377
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
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| 16. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Svenskarna som överlevde tsunamin mår relativt bra : Uppföljning sex år efter katastrofen 2004
- 2012
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:37, s. 1607-1609
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Tidskriftsartikel (refereegranskat)abstract
- Hälsoläget i hela den undersökta populationen av överlevande svenskar sex år efter flodvågskatastrofen 2004 ter sig relativt gott.Jämfört med den förra undersökningen tre år efter tsunamin finns indikationer på en viss fortsatt återhämtning.Kvinnor visar besvär i något större utsträckning än män.En minoritet har fortfarande problem, i synnerhet de som var utsatta för livshot. Fördjupade studier kommer att belysa faktorer av betydelse för olika vägar till återhämtning.
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| 17. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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The effect of Traumatic Bereavement on Tsunami-Exposed Survivors
- 2009
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 22:6, s. 497-504
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen months after the 2004 tsunami, mental health outcome was assessed in 187 bereaved relatives, 308 bereaved friends, and in 3,020 nonbereaved Swedish survivors. Of the bereaved relatives, 41% reported posttraumatic stress reactions and 62% reported impaired general mental health. Having been caught or chased by the tsunami in combination with bereavement was associated with increased posttraumatic stress reactions. Complicated grief reactions among relatives were almost as frequent as posttraumatic stress reactions. The highest levels of psychological distress were found among those who had lost children. Traumatic bereavement, in combination with exposure to life danger, is probably a risk factor for mental health sequelae after a natural disaster.
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| 18. |
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| 19. |
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| 20. |
- Bergh Johannesson, Kerstin, 1949-
(författare)
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Traumatic Exposure, Bereavement and Recovery among Survivors and Close Relatives after Disasters
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- International studies of disasters indicate the risk for developing posttraumatic stress reactions among survivors is high. Modern life implicates increased traveling. During the last decades a large number of Swedish citizens were confronted with disasters taking place outside of their country. The prevalence of trauma reactions in a population that does not normally experience natural disasters, but are able to return to a community unaffected by the catastrophe, is not well studied. In addition, the effects of bereavement after traumatic circumstances have not been satisfactorily explored. Longitudinal studies on the effects of natural disasters are underrepresented and there are few studies investigating the course of recovery after traumatic exposure. The aim for this thesis was to examine long-term post-traumatic stress reactions, mental health, and complicated grief after disaster exposure and traumatic bereavement. Data from returned questionnaires were analysed from bereaved Italian and Swedish relatives 18 months after the Linate airplane disaster 2001, and at 14 months and three years from Swedish travelers returning from Southeast Asia after the 2004 tsunami disaster, and from home staying bereaved relatives within the second year after the tsunami disaster. The main outcome measures were GHQ-12, IES-R and Inventory of Complicated Grief. The findings indicated many survivors were resilient and had ability to recover, but severe exposure to a disaster had considerable impact on psychological distress. Life threat was associated with higher levels of post-traumatic stress reactions, and increased the risk for affected mental health and suicidal ideation. Loss in combination with severe life threat exposure indicated a further increased risk of posttraumatic stress reactions and for complicated grief; this should be considered a substantial risk factor for general mental health. Loss of close relatives, especially loss of children, was associated with higher levels of posttraumatic stress and created a greater risk for complicated grief. Many survivors recovered over time; however, severe exposure and traumatic loss appeared to slow the recovery process. The findings have implications for government and health agencies, regarding the importance of knowledge and awareness of these risks for health, and for organizational structure, training, and accessibility of support and adequate treatment.
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| 21. |
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| 22. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Tsunami-exposed tourist survivors : Signs of recovery in an 3-year perspective
- 2011
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Ingår i: Journal of Nervous and Mental Disease. - 0022-3018 .- 1539-736X. ; 199:3, s. 162-169
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Tidskriftsartikel (refereegranskat)abstract
- Long-term follow-up after disaster exposure indicates increased rates of psychological distress. However, trajectories and rates of recovery in large samples of disaster-exposed survivors are largely lacking. A group of 3457 Swedish survivors temporarily on vacation in Southeast Asia during the 2004 tsunami were assessed by postal questionnaire at 14 months and 3 years after the tsunami regarding post-traumatic stress reactions (IES-R) and general mental health (GHQ-12). There was a general pattern of resilience and recovery 3 years postdisaster. Severe exposure and traumatic bereavement were associated with increased post-traumatic stress reactions and heightened risk for impaired mental health. The rate of recovery was lower among respondents exposed to life threat and among bereaved. Severe trauma exposure and bereavement seem to have considerable long-term impact on psychological distress and appear to slow down the recovery process. Readiness among health agencies for identification of symptoms and provision of interventions might facilitate optimal recovery.
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| 23. |
- Dyster-Aas, Johan, et al.
(författare)
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Impact of physical injury on mental health after the 2004 Southeast Asia tsunami
- 2012
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 66:3, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- Background : The risk of developing enduring post-traumatic stress reactions and mental health problems in the aftermath of disasters is substantial. However, there are inconsistencies regarding the contribution of physical injury as an independent risk factor for developing psychiatric morbidity after disasters. Aims : The aim was to assess whether physical injury was associated with post-traumatic stress reactions and general mental health after adjusting for perceived life-threat in the aftermath of the 2004 tsunami. Methods : A sample of 1501 highly exposed survivors from the 2004 Southeast Asia tsunami was selected from a cohort of Swedish survivors surveyed 14 and 36 months after the event. The impact of physical injury on post-traumatic stress and general mental health was assessed by regression models accounting for subjective life-threat. Results : Physical injury was associated with higher levels of post-traumatic stress reactions and poorer general mental health. These associations were observed at both 14 and 36 months after the disaster. Conclusions : Physical injury has a specific contribution to the association between traumatic experience and both post-traumatic stress reactions and general mental health in victims of the 2004 tsunami. The effect is stable over several years.
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| 24. |
- Edlund, Per, et al.
(författare)
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Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-1
- 2011
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer. Patients and methods. After a first standard dosed FEC course (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/mg(2) and cyclophosphamide 600 mg/m(2)), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2 7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered). Results. Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III-IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. Conclusion. Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.
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| 25. |
- Einarsson, Snorri, 1973, et al.
(författare)
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Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.
- 2017
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:8, s. 1621-1630
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Tidskriftsartikel (refereegranskat)abstract
- Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women?An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF.Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women.A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included.Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only.In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found.The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2.The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results.The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose.ClinicalTrials.gov number, NCT01566929.23-03-2012.05-10-2010.
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| 26. |
- Ejlertsen, Bent, et al.
(författare)
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Similar efficacy for ovarian ablation compared with cyclophosphamide, methotrexate, and fluorouracil: from a randomized comparison of premenopausal patients with node-positive, hormone receptor-positive breast cancer
- 2006
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Ingår i: J Clin Oncol. - : American Society of Clinical Oncology (ASCO). - 1527-7755. ; 24:31, s. 4956-4962
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Tidskriftsartikel (refereegranskat)abstract
- To compare the efficacy of ovarian ablation versus chemotherapy in early breast cancer patients with hormone receptor–positive disease. Patients and Methods We conducted an open, randomized, multicenter trial including premenopausal breast cancer patients with hormone receptor–positive tumors and either axillary lymph node metastases or tumors with a size of 5 cm or more. Patients were randomly assigned to ovarian ablation by irradiation or to nine courses of chemotherapy with intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) administered every 3 weeks. Results Between 1990 and May 1998, 762 patients were randomly assigned, and the present analysis is based on 358 first events. After a median follow-up time of 8.5 years, the unadjusted hazard ratio for disease-free survival in the ovarian ablation group compared with the CMF group was 0.99 (95% CI, 0.81 to 1.22). After a median follow-up time of 10.5 years, overall survival (OS) was similar in the two groups, with a hazard ratio of 1.11 (95% CI, 0.88 to 1.42) for the ovarian ablation group compared with the CMF group. Conclusion In this study, ablation of ovarian function in premenopausal women with hormone receptor–positive breast cancer had a similar effect to CMF on disease-free and OS. No significant interactions were demonstrated between treatment modality and hormone receptor content, age, or any of the well-known prognostic factors.
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| 27. |
- Gejervall, Ann-Louise, 1963, et al.
(författare)
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Electro-acupuncture versus conventional analgesia: a comparison of pain levels during oocyte aspiration and patients' experiences of well-being after surgery
- 2005
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Ingår i: Hum Reprod. ; 20:3, s. 728-35
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The primary aims were to compare the pain-relieving effect and post-operative well-being between electro-acupuncture analgesia (EA) and conventional analgesia (CA) comprising opiates. Further aims were to compare time for mobilization, and costs for time and drug consumption. METHODS: In all, 160 women undergoing IVF were randomized, according to a computer-generated list, to EA or CA. Well-being was evaluated with the State Trait Anxiety Inventory (STAI). Pain and subjective expectations and experiences were recorded on a visual analogue scale (VAS). Time and drug consumption were recorded. RESULTS: Although VAS pain ratings were significantly higher at oocyte aspiration (P < 0.0001) and after retrieval (P < 0.01) in the EA than in the CA group, they were similar 60 min after surgery. Both groups had similar STAI well-being scores. The EA group was significantly less tired and confused than the CA group after oocyte aspiration. No significant differences in time and costs for drug consumption were noted. CONCLUSION: EA cannot generally be recommended as a pain-relieving method at oocyte aspiration but might be an alternative for women desiring a non-pharmacological method. An advantage of EA is less post-operative tiredness and confusion compared with CA.
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| 28. |
- Haange, S. B., et al.
(författare)
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Ring Trial on Quantitative Assessment of Bile Acids Reveals a Method- and Analyte-Specific Accuracy and Reproducibility
- 2022
-
Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:7
-
Tidskriftsartikel (refereegranskat)abstract
- Bile acids are a key mediator of the molecular microbiome-host interaction, and various mass spectrometry-based assays have been developed in the recent decade to quantify a wide range of bile acids. We compare existing methodologies to harmonize them. Methodology for absolute quantification of bile acids from six laboratories in Europe were compared for the quantification of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) and conjugated products glycocholic acid (GCA) and taurocholic acid (TCA). For the bacterially modified secondary bile acids, the quantification of deoxycholic acid (DCA) and lithocholic acid (LCA) was compared. For the murine bile acids, we used the primary muricholic acids (alpha-MCA and, beta-MCA) and the intestinally produced secondary bile acid muricholic (omega-MCA). The standards were spiked into methanol:water (1:1) mix as well as in human and murine serum at either low concentration range (150-3000 nM) or high concentration range (1500-40,000 nM). The precision was better for higher concentrations. Measurements for the hydrophobic unconjugated bile acids LCA and omega-MCA were the most challenging. The quality assessments were generally very similar, and the comprehensive analyses demonstrated that data from chosen locations can be used for comparisons between studies.
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| 29. |
- Heir, Trond, et al.
(författare)
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Tsunami-affected Scandinavian tourists : Disaster exposure and post-traumatic stress symptoms
- 2011
-
Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:1, s. 9-15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of short- and long-term mental effects of natural disasters have reported a high prevalence of post-traumatic stress. Less is known about disaster-exposed tourists repatriated to stable societies. Aims: To examine the association between exposure to the 2004 Southeast Asian tsunami and symptoms of post-traumatic stress in three Scandinavian tourist populations. Methods: Postal survey of Norwegian, Danish and Swedish Southeast Asia tourists registered by the police when arriving at national airports. Follow-up time was 6 (Norway), 10 (Denmark) and 14 months (Sweden) post-disaster; 6772 individuals were included and categorized according to disaster exposure: danger exposed (caught or chased by the waves), non-danger exposed (other disaster-related stressors) and non-exposed. Outcome measures were the Impact of Event Scale-Revised (IES-R) and Post Traumatic Stress Disorder Check List (PCL). Results: Danger exposed reported more post-traumatic stress than non-danger exposed, and the latter reported more symptoms than non-exposed (each P<0.001). Comparison of the Norwegian and Swedish data suggested that symptoms were attenuated at 14 months follow-up (P<0.001). Female gender and low education, but not age, predicted higher levels of symptoms. Conclusions: Disaster-exposed tourists repatriated to unaffected home environments show long-term post-traumatic stress disorder symptoms related to the severity of exposure.
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| 30. |
- Karlström, Per Olof, et al.
(författare)
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Reducing the number of embryos transferred in Sweden-impact on delivery and multiple birth rates
- 2007
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 22:8, s. 2202-2207
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reduction of the number of embryos transferred has been introduced to decrease the multiple birth rates (MBRs) after IVF and the associated risks for the children. The aim of this report is to present the effect of two steps in reduction of the number of embryos transferred, when applied in the majority of the patients, on national data for delivery and MBR after IVF in Sweden. Methods: This observational study is based on annual reports from all IVF clinics in Sweden to the National Board of Health and Welfare for the time period 1991-2004. Results: The main finding is that despite a successive reduction in the number of embryos transferred, delivery rates were maintained at around 26% while MBR decreased dramatically, from about 35% to around 5%. The same pattern was noticed, independent of age, for all women below 40. In comparison with the USA, lower delivery and MBR were noted for Sweden whereas a higher 'birth per embryo transferred' was found. Conclusions: Single embryo transfer (SET) results in satisfactory delivery rates and a dramatic decrease in the MBRs, also when applied on a broad scale. The experience from Sweden ought to encourage other countries to introduce SET more widely.
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| 31. |
- Koh, Ara, et al.
(författare)
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Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1
- 2018
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 175:4
-
Tidskriftsartikel (refereegranskat)abstract
- Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38 gamma MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
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| 32. |
- Koopen, A., et al.
(författare)
-
Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study
- 2022
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:8, s. 1577-1587
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.
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| 33. |
- Laudette, Marion, et al.
(författare)
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Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function
- 2023
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1537-1552
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Tidskriftsartikel (refereegranskat)abstract
- Aims Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CMPcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. Methods and results Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. Conclusion PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
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| 34. |
- Lindahl, Olof A, et al.
(författare)
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A tactile resonance sensor for prostate cancer detection – evaluation on human prostate tissue
- 2021
-
Ingår i: Biomedical Engineering & Physics Express. - : Institute of Physics (IOP). - 2057-1976. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer surgery risks erectile problems and incontinence for the patient. An instrument for guiding surgeons to avoid nerve bundle damage and ensure complete cancer removal is desirable. We present a tactile resonance sensor made of PZT ceramics, mounted in a 3D motorized translation stage for scanning and measuring tissue stiffness for detecting cancer in human prostate. The sensor may be used during surgery for guidance, scanning the prostate surface for the presence of cancer, indicating migration of cancer cells into surrounding tissue. Ten fresh prostates, obtained from patients undergoing prostate cancer surgery, were cut into 0.5 cm thick slices. Each slice was measured for tissue stiffness at about 25 different sites and compared to histology for validation cancer prediction by stiffness. The statistical analysis was based on a total of 148 sites with non-cancer and 40 sites with cancer. Using a generalized linear mixed model (GLMM), the stiffness data predicted cancer with an area under the curve of 0.74, after correcting for overfitting using bootstrap validation. Mean prostate stiffness on the logarithmic scale (p = 0.015) and standardized Z-scores (p = 0.025) were both significant predictors of cancer. This study concludes that stiffness measured by the tactile resonance sensor is a significant predictor of prostate cancer with potential for future development towards a clinical instrument for surgical guidance.
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| 35. |
- Makki, Kassem, et al.
(författare)
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6 alpha-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice
- 2023
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 72:2, s. 314-324
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet. Design To assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects. Results We show that oligofructose sustains the production of 6 alpha-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6 alpha-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6 alpha-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism. Conclusion Modulation of the gut microbiota with oligofructose enriches bacteria involved in 6 alpha-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.
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| 36. |
- Mardinoglu, Adil, 1982, et al.
(författare)
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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
- 2018
-
Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 27:3
-
Tidskriftsartikel (refereegranskat)abstract
- A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
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| 37. |
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| 38. |
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| 39. |
- Michel, Per-Olof
(författare)
-
Psykotraumatologi
- 2018. - 3
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Människosläktet har genom årtusenden exponerats för olyckor och naturkatastrofer. Transportolyckor och andra tekniska katastrofer, krig och flyktingtrauman, terrorhändelser liksom interpersonellt våld och traumatiska övergrepp under uppväxten kan utgöra påfrestningar under människors liv samt leda till svåra hälsoeffekter.Denna tredje upplaga av Psykotraumatologi riktar sitt fokus mot den utveckling som skett under senaste decenniet när det gäller forskningen inom området. Sålunda beskrivs hur människor reagerar på hot och på faktorer som både kan öka risken för och motverka utvecklingen av traumatisk stress. Komplicerade sorgereaktioner och traumarelaterade tillstånd beskrivs ingående både när det gäller barn och vuxna. Vidare är avsnitten om neurobiologi, krisstöd i akutfas och behandling uppdaterade.Syftet med Psykotraumatologi är att utgöra en samlad kunskapskälla för den som behöver det i sin utbildning och fortbildning. På så sätt kan alla som i sin profession kommer i kontakt med potentiellt traumatiserade individer, till exempel inom hälso- och sjukvården, skolväsendet samt inom kommunernas socialtjänst ha nytta av boken.
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| 40. |
- Michel, Per-Olof, et al.
(författare)
-
Psykotraumatologi
- 2010. - 2:1
-
Bok (övrigt vetenskapligt/konstnärligt)
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| 41. |
- Michel, Per-Olof, et al.
(författare)
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Överlevande svenskar efter tsunamin : 3-årsuppföljning visar relativt god hälsa – men många har problem
- 2009
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 41:106, s. 2604-2606
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The mental health situation among the population of Swedish tsunami survivors investigated three years after the disaster was relatively good, and appeared to have improved compared to the earlier investigation in spring 2006, 14-months post-tsunami. Women appeared to suffer from reactions and discomfort more than men did. Even though the health situation was good for the majority of participants, there were still a considerable minority with problems after the tsunami, for instance, the most seriously stricken who were exposed to a life-threatening situation or who had lost loved ones. Further studies will determine how their health develops.
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| 42. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 43. |
- Molinaro, Antonio, et al.
(författare)
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Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality
- 2023
-
Ingår i: JACC: Heart Failure. - 2213-1779 .- 2213-1787. ; 11:7, s. 810-821
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure. Objectives: The authors aimed to explore whether ImP is associated with heart failure and mortality. Methods: ImP serum measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates. Results: ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01). Conclusions: The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.
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| 44. |
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| 45. |
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| 46. |
- Nordenskjöld, Bo, 1940-, et al.
(författare)
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Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: results from a randomized trial
- 2005
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Ingår i: J Natl Cancer Inst. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 97:21, s. 1609-10
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Tidskriftsartikel (refereegranskat)abstract
- From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94; P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed.
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| 47. |
- Papakonstantinou, Antroula, et al.
(författare)
-
Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer : Results from the phase 3 PANTHER trial
- 2020
-
Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 126:6, s. 1175-1182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse–free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up. Results: There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P =.231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups. Conclusions: The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.
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| 48. |
- Pennisi, Grazia, et al.
(författare)
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ANGPTL3 Downregulation Increases Intracellular Lipids by Reducing Energy Utilization.
- 2024
-
Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636.
-
Tidskriftsartikel (refereegranskat)abstract
- ANGPTL3 (angiopoietin-like protein 3) is a circulating protein with a key role in maintaining lipoprotein homeostasis. A monoclonal antibody against ANGPTL3 is an approved and well-tolerated treatment to reduce lipoproteins in familial hypercholesterolemia homozygotes. However, the reduction of hepatic ANGPTL3 synthesis using an antisense oligonucleotide unexpectedly resulted in a dose-dependent increase in liver lipid content and circulating transaminases, resulting in the termination of the clinical trial. Meanwhile, the use of silencing RNAs remains an area of active investigation. Our study sought to investigate whether intracellular downregulation of ANGPTL3 may lead to a primary increase in neutral lipids within the hepatocyte.We downregulated ANGPTL3 by silencing RNA in primary human hepatocytes 3-dimensional spheroids, HepG2/LX-2 3-dimensional spheroids, and in HepG2, Hep3B2, and Huh7 cultured in 2 dimensions.ANGPTL3 downregulation increased neutral lipids in all models investigated. Interestingly, ANGPTL3 induced lower intracellular deiodinase type 1 protein levels resulting in a reduction in beta-oxidation and causing an increase in triglycerides stored in lipid droplets.In conclusion, intracellular ANGPTL3 downregulation by silencing RNA led to an increase in triglycerides content due to a reduction in energy substrate utilization resembling a primary intracellular hepatocyte hypothyroidism.
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| 49. |
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Psykotraumatologi : bedömning, bemötande och behandling av stresstillstånd
- 2010. - 2
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Nya allvarliga händelser drabbar kontinuerligt människor runt om i världen och även i vårt land. Det gör att ämnet psykotraumatologi ständigt är aktuellt och som följd av att kunskapsmängden inom området har ökat under senare år har det blivit nödvändigt att sammanfatta det psykotraumatologiska fältet på nytt.I denna omarbetade och utökade upplaga har författarna behållit utgångspunkten med det psykiska traumat sett ur ett historiskt och socialt sammanhang, grundat på ett holistiskt synsätt. Vi beskriver hur den normala och den traumatiska stressen påverkar människan. Faktorer som kan verka skyddande och sådana som kan bidra till att utveckla psykiska störningar skildras även. Vi beskriver ingående krisstöd i akutfas och riktlinjer för modern traumafokuserad behandling.Syftet med boken är att utgöra en samlad kunskapskälla på svenska språket för den som behöver det i sin utbildning och fortbildning. De som på så sätt kan ha nytta av boken är personal i hälso- och sjukvården, kuratorer, läkare, psykologer, skötare inom vuxen-, barn- och ungdomspsykiatrin, primärvården och företagshälsovården samt även befattningshavare inom kommunernas krisstödsorganisation. Andra som kan ha nytta av boken är alla som i sin profession kommer i kontakt med traumatiserade individer.Boken kan med fördel användas både som lärobok och uppslagsbok.
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| 50. |
- Ruiz, Mario, 1984, et al.
(författare)
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Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cells and organisms require proper membrane composition to function and develop. Phospholipids are the major component of membranes and are primarily acquired through the diet. Given great variability in diet composition, cells must be able to deploy mechanisms that correct deviations from optimal membrane composition and properties. Here, using lipidomics and unbiased proteomics, we found that the embryonic lethality in mice lacking the fluidity regulators Adiponectin Receptors 1 and 2 (AdipoR1/2) is associated with aberrant high saturation of the membrane phospholipids. Using mouse embryonic fibroblasts (MEFs) derived from AdipoR1/2-KO embryos, human cell lines and the model organism C. elegans we found that, mechanistically, AdipoR1/2-derived sphingosine 1-phosphate (S1P) signals in parallel through S1PR3-SREBP1 and PPARγ to sustain the expression of the fatty acid desaturase SCD and maintain membrane properties. Thus, our work identifies an evolutionary conserved pathway by which cells and organisms achieve membrane homeostasis and adapt to a variable environment.
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