| 1. |
- Blomqvist, Fredrik Lennart Rune, 1947, et al.
(författare)
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Platelet aggregation in healthy women during normal pregnancy - a longitudinal study.
- 2019
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Ingår i: Platelets. - : Informa UK Limited. - 1369-1635 .- 0953-7104. ; 30:4, s. 438-444
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Tidskriftsartikel (refereegranskat)abstract
- Increased platelet activation is involved in obstetric complications such as preeclampsia and intrauterine growth retardation. It is of interest to study platelet aggregation during pregnancy, since increased aggregation theoretically could be a mechanism associated with placenta-mediated complications, which possibly could be prevented by drugs inhibiting platelet aggregation. There are, however, few robust studies describing platelet aggregation during normal pregnancy. The present longitudinal study was performed in order to study platelet aggregation during normal pregnancy resulting in a healthy child, during the puerperium and in nonpregnant, fertile women. Healthy, nonsmoking, pregnant women (n=104), aged under 39years and with BMI <35, were followed during pregnancy and postpartum. Twenty-seven nonpregnant, non-puerperal, fertile women were studied for comparison. Platelet aggregation was determined with multiple electrode impedance aggregometry and analyzed at inclusion, 4 times during pregnancy and after at least 3 months postpartum. Platelet aggregation postpartum was compared with gestational weeks 8-15 and 37-40, respectively, and with nonpregnant, fertile women. Hemoglobin, leucocyte count, platelet count, prothrombin time, and activated partial thromboplastin time were determined at inclusion in order to verify normal hemostasis. Activation of platelets by arachidonic acid, adenosine diphosphate (ADP), and thrombin receptor activating peptide (trap-6) resulted in less aggregation during pregnancy, compared with postpartum (p<0.03-<0.001). Platelet aggregation following activation by collagen was unchanged. A minor increase in aggregation as pregnancy continued was found related to ADP (p<0.021). Positive correlations were found between platelet counts and platelet aggregation. Postpartum platelet aggregation after activation with arachidonic acid, collagen, and trap-6 was lower than in the non-puerperal fertile state. Other hemostatic analyses were normal. In conclusion, there is a minor decrease in platelet aggregation after activation with arachidonic acid, trap-6, and ADP, measured with multiple electrode impedance aggregometry during normal pregnancy resulting in healthy babies, compared with the postpartum period. The small changes in platelet aggregation may be a consequence of a minor decrease in platelet count and probably lack clinical significance under normal conditions. Interindividual variations at certain time-points are substantial, which limits the usefulness of the multiple electrode impedance aggregometry for determining minor changes in platelet function.
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| 2. |
- Blomqvist, Lennart, 1947, et al.
(författare)
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Acetylsalicylic acid does not prevent first-trimester unexplained recurrent pregnancy loss: A randomized controlled trial
- 2018
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:11, s. 1365-1372
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Recurrent pregnancy loss occurs in about 1% of fertile couples. Without proper evidence for an effect, different treatments have been used when no etiological factor has been detected. The present trial is the first randomized trial to compare 75 mg acetylsalicylic acid with placebo for women with recurrent pregnancy loss. Material and methods: This randomized, double-blind, placebo-controlled trial was conducted at a single center between 2008 and 2015. Recurrent pregnancy loss was defined as at least 3 consecutive first-trimester miscarriages within the couple. Women < 40 years old with a body mass index < 35 kg/m(2) were eligible if the workup was negative. Randomization was through a third party, who manufactured and delivered the study drugs, and occurred when fetal heartbeat was detected, to either 75 mg acetylsalicylic acid or placebo; 200 women in each group. Group allocation was concealed until all the study participants had a pregnancy outcome registered. All women attended the same control program. Primary outcome was live birth. Statistical analyses were according to intention-to-treat. Results: All 400 women completed the follow up. Live birth rate was 83.0% (n=166) and 85.5% (n=171) for the acetylsalicylic acid and placebo groups, respectively (P=0.58). The difference was -2.5% (95% CI -10.1% to 5.1%). The risk ratio was 0.97 (95% CI 0.89-1.06). Conclusions: Treatment with acetylsalicylic acid did not prevent recurrent miscarriage in women with at least three consecutive miscarriages in the first trimester, of unknown reasons and in the same relationship. The fertility prognosis is very good, the live birth rate being > 80% with or without acetylsalicylic acid.
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| 3. |
- Blomqvist, Lennart, 1947
(författare)
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Recurrent unexplained first-trimester miscarriage. Effects of acetylcalicylic acid, platelet aggregation and thyroid disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recurrent unexplained first-trimester miscarriage. Effects of acetylsalicylic acid, platelet aggregation and thyroid disease. Lennart Blomqvist, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden, 2019. Background/Aims: Recurrent pregnancy loss (RPL) occurs in 1-2% of fertile couples and about 50% of cases are unexplained. Impaired placental circulation, increased platelet aggregation, immunological factors and thyroid autoimmunity have been suggested to be involved. Other placenta-mediated complications have been reduced by inhibition of platelet aggregation with acetylsalicylic acid (ASA). The effect of ASA on RPL has been unclear. These studies aimed at investigating the effect of ASA treatment on RPL and arachidonic acid (AA)-induced platelet aggregation in women with RPL, as well as the effect of thyroid function by analyzing Thyroid Stimulating Hormone (TSH) and thyroid peroxidase antibodies (TPO-ab). Methods: Women (n=640) with at least three unexplained first-trimester miscarriages were screened for inclusion in a single-center, randomized, placebo-controlled trial (the ASA-RCT, Paper I). Four hundred women were given either 75 mg ASA or placebo daily, beginning at gestational week (gw) 6-7, when fetal heartbeat was detected by vaginal ultrasound. Treatment ended at the latest at gw 36. Treatment compliance was determined by analysis of AA-induced platelet aggregation using multiple electrode impedance aggregometry. All women underwent the same follow-up. Primary outcome was live birth rate (LBR). In order to define reference values for the multiple electrode impedance aggregometry (the Multiplate analyzer), a longitudinal study was conducted including 79 healthy, non-smoking pregnant women with normal pregnancies (Paper II). Platelet aggregation induced by AA, adenosine diphosphate (ADP), thrombin receptor activating peptide 6 (TRAP) and collagen (COL) were determined four times during pregnancy and three months postpartum. From the randomized population, 176 and 177 women, respectively, with normal AA-induced platelet aggregation before pregnancy and treated with ASA or placebo, were studied (Paper III). Platelet aggregation was determined before and during pregnancy and results in the randomized groups were compared with one another, as well as with those in the healthy controls from Paper II. From the screened and eligible population, 495 women with complete thyroid test analyses [thyroid stimulating hormone (TSH), free thyroxine (T4) and thyroid peroxidase antibodies TPO-ab] before pregnancy were included. Risk factors for a new miscarriage were studied, in particular associations with TPO-ab and TSH in the upper normal range. Results: In the ASA-RCT, all 400 randomized women completed the follow-up. LBR were 83.0% and 85.5% in the ASA and placebo groups, respectively. The mean difference was -2.5% (95% CI to -10.1% to 5.1%). The risk ratio was 0.97 (95% CI 0.89 to 1.06). In the longitudinal study of platelet aggregation during normal pregnancy, activation of platelets by AA, ADP and TRAP resulted in a minor decrease in platelet aggregation during pregnancy, compared with postpartum. COL-induced platelet aggregation was unchanged. A minor increase in platelet aggregation as pregnancy continued was found related to ADP. There were no significant differences in AA-induced platelet aggregation when placebo-treated women with RPL were compared with healthy women with normal pregnancies. ASA treatment significantly reduced platelet aggregation during pregnancy, compared with before pregnancy. Gradually increased platelet aggregation was seen in the majority of ASA-treated women as pregnancy progressed. There were only two complete non-responders to ASA. Miscarriage occurred more often in women with than without TPO-ab (25.7% vs 17.5%). There was no association between TSH in the upper normal range and a new miscarriage. Potential risk factors for a new miscarriage were age, number of previous miscarriages and presence of TPO-ab. Conclusions: ASA does not prevent a new miscarriage in women with at least three previous first-trimester miscarriages. AA-induced platelet aggregation seems to be similar in women with RPL and in healthy women with normal pregnancies. ASA, 75 mg daily, decreases AA-induced platelet aggregation in most women during pregnancy, but the effect diminishes as pregnancy progresses. TPO-ab, but not TSH in the upper normal range, may be associated with an increased risk of a new miscarriage.
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| 4. |
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| 5. |
- Bratt, Ola, et al.
(författare)
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Satsa på MRT för diagnostik av prostatacancer.
- 2015
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 1652-7518 .- 0023-7205. ; 112:Apr 20, s. DFZ3-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- D'Souza, Nigel, et al.
(författare)
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Definition of the Rectum An International, Expert-based Delphi Consensus
- 2019
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Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 270:6, s. 955-959
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Tidskriftsartikel (refereegranskat)abstract
- Background: The wide global variation in the definition of the rectum has led to significant inconsistencies in trial recruitment, clinical management, and outcomes. Surgical technique and use of preoperative treatment for a cancer of the rectum and sigmoid colon are radically different and dependent on the local definitions employed by the clinical team. A consensus definition of the rectum is needed to standardise treatment. Methods: The consensus was conducted using the Delphi technique with multidisciplinary colorectal experts from October, 2017 to April, 2018. Results: Eleven different definitions for the rectum were used by participants in the consensus. Magnetic resonance imaging (MRI) was the most frequent modality used to define the rectum (67%), and the preferred modality for 72% of participants. The most agreed consensus landmark (56%) was "the sigmoid take-off,'' an anatomic, image-based definition of the junction of the mesorectum and mesocolon. In the second round, 81% of participants agreed that the sigmoid take-off as seen on computed tomography or MRI achieved consensus, and that it could be implemented in their institution. Also, 87% were satisfied with the sigmoid take-off as the consensus landmark. Conclusion: An international consensus definition for the rectumis the point of the sigmoid take-off as visualized on imaging. The sigmoid take-off can be identified as the mesocolon elongates as the ventral and horizontal course of the sigmoid on axial and sagittal views respectively on cross-sectional imaging. Routine application of this landmark during multidisciplinary team discussion for all patients will enable greater consistency in tumour localisation.
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| 7. |
- Elliot, Anders H., et al.
(författare)
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An audit of performance, interpretation, and influence of pretherapeutic MRI in rectal cancer : a Swedish population-based cohort study
- 2019
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Ingår i: Acta Radiologica. - : SAGE PUBLICATIONS LTD. - 0284-1851 .- 1600-0455. ; 60:8, s. 955-961
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Tidskriftsartikel (refereegranskat)abstract
- Background: The performance of magnetic resonance imaging (MRI) interpretation and communication of findings and its implication on treatment decisions has not fully been explored in rectal cancer.Purpose: To investigate in a region the adherence to MRI protocol standards and the relation between MRI interpretation and selection to preoperative therapy in rectal cancer.Material and Methods: Data on consecutive patients who underwent elective rectal cancer surgery in the region from January to June 2010 were obtained from the National Colorectal Cancer Registry. Pretherapeutic MRI images were re-evaluated. Agreement between the original reports and the re-evaluation was compared using Cohen's kappa coefficient.Results: Among the 94 patients included, 81 (86%) had pretherapeutic MRI in accordance with defined imaging guidelines. In 34% of the original MR reports, data on extramural venous invasion (mrEMVI) and mrT category were not reported. Complete tumor staging was not possible because of missing data in 33 (35%) of the patients. The agreement between the original MR reports and the re-evaluation regarding tumor stage was moderate (kappa = 0.48). For decided treatment compared to recommended preoperative treatment according to the re-evaluation, the agreement was fair (kappa = 0.33).Conclusion: Established MRI protocol standards were not universally applied. Missing data and inadequacies in original MRI reports resulted in moderate agreement between the original report and the re-evaluation indicating a risk of inappropriate treatment selection. The results call for further educational efforts in rectal cancer MRI acquisition and repeated audits of image protocol adherence and interpretation quality.
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| 8. |
- Gustafsson, Mats, et al.
(författare)
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Att överväga geologin. En idéskrift om geovetenskapliga värden i vägplaneringen
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Landskapets geologi, former och andra naturgivna egenskaper har en förhållandevis undanskymd roll i dagens infrastrukturplanering jämfört med den vikt som läggs vid biologiska och ekologiska företeelser och egenskaper. Många gånger är det dessutom endast extremföreteelser som lyfts fram i samband med infrastrukturplaneringen medan det så kallade vardagslandskapet får träda tillbaka, trots att det har en viktig roll för förståelsen av landskapet. Föreliggande rapport visar ett angreppssätt där geovetenskapliga värden inom ett givet geografiskt område definieras i olika teman utifrån en kombination av fältstudier samt historiska och moderna kartor. De tema som används i rapporten baseras delvis på begreppet geodiversitet och omfattar geovetenskapliga egenvärden/pedagogiska värden, ekologiska geovärden, kulturhistoriska geovärden samt geovärden med betydelse för fritid och rekreation. Arbetet har utförts inom det geologiska kartbladet Linköping NV.
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| 9. |
- Herter, Eva K., et al.
(författare)
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WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines
- 2019
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Ingår i: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 139:6, s. 1373-1384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic wounds represent a major and growing health and economic burden worldwide. A better understanding of molecular mechanisms of normal as well as impaired wound healing is needed to develop effective treatment. Herein we studied the potential role of long noncoding RNA LOC100130476 in skin wound repair. LOC100130476 is an RNA polymerase IIeencoded polyadenylated transcript present in both cytoplasm and nucleus. We found that its expression was lower in wound-edge keratinocytes of human chronic wounds compared to normal wounds of healthy donors and intact skin. In cultured keratinocytes, LOC100130476 expression was induced by TGF-beta signaling. By reducing LOC100130476 expression with antisense oligos or activating its transcription with CRISPR/Cas9 Synergistic Activation Mediator system, we showed that LOC100130476 restricted the production of inflammatory chemokines by keratinocytes, while enhancing cell migration. In line with this, knockdown of LOC100130476 impaired re-epithelization of human ex vivo wounds. Based on these results, we named LOC100130476 wound and keratinocyte migration-associated long noncoding RNA 2 (WAKMAR2). Moreover, we identified a molecular network that may mediate the biological function of WAKMAR2 in keratinocytes using microarray. In summary, our data suggest that WAKMAR2 is an important regulator of skin wound healing and its deficiency may contribute to the pathogenesis of chronic wounds.
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| 10. |
- Jäderling, Fredrik, et al.
(författare)
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Accuracy in local staging of prostate cancer by adding a three-dimensional T2-weighted sequence with radial reconstructions in magnetic resonance imaging
- 2018
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Ingår i: Acta Radiologica Open. - : Sage Publications. - 2058-4601. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting the use of magnetic resonance imaging (MRI) in prostate cancer detection has been established, but its accuracy in local staging is questioned. Purpose: To investigate the additional value of multi-planar radial reconstructions of a three-dimensional (3D) T2-weighted (T2W) MRI sequence, intercepting the prostate capsule perpendicularly, for improving local staging of prostate cancer. Material and Methods: Preoperative, bi-parametric prostate MRI examinations in 94 patients operated between June 2014 and January 2015 where retrospectively reviewed by two experienced abdominal radiologists. Each patient was presented in two separate sets including diffusion-weighted imaging, without and with the 3D T2W set that included radial reconstructions. Each set was read at least two months apart. Extraprostatic tumor extension (EPE) was assessed according to a 5-point grading scale. Sensitivity and specificity for EPE was calculated and presented as receiver operating characteristics (ROC) with area under the curve (AUC), using histology from whole-mount prostate specimen as gold standard. Inter-rater agreement was calculated for the two different reading modes using Cohen's kappa. Results: The AUC for detection of EPE for Readers 1 and 2 in the two-dimensional (2D) set was 0.70 and 0.68, respectively, and for the 2D+3D set 0.62 and 0.65, respectively. Inter-rater agreement (Reader 1 vs. Reader 2) on EPE using Cohen's kappa for the 2D and 2D+3D set, respectively, was 0.42 and 0.17 (i.e. moderate and poor agreement, respectively). Conclusion: The addition of 3D T2W MRI with radial reconstructions did not improve local staging in prostate cancer.
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