| 1. |
- Hardell, Elin, et al.
(author)
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Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas
- 2017
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In: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 41:9, s. 1231-1237
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Journal article (peer-reviewed)abstract
- Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.
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| 2. |
- Krarup, Anne L., et al.
(author)
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Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain.
- 2013
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In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:3, s. 274-84
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Journal article (peer-reviewed)abstract
- Abstract Objective. Many patients with nonerosive reflux disease (NERD) have insufficient relief on proton pump inhibitors (PPIs). Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 (TRPV1) antagonists. Aim. To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients. Material and methods. Enrolled patients had NERD and a partial PPI response (moderate-to-severe heartburn or regurgitation ≥3 days/week before enrolment despite ≥6 weeks' PPI therapy). Fourteen patients (21-69 years, 9 women) were block-randomized into this placebo-controlled, double-blinded, crossover study examining efficacy of a single dose (95 mg) of AZD1386. On treatment days, each participant's esophagus was stimulated with heat, distension, and electrical current at teaching hospitals in Denmark and Sweden. Heat and pressure pain served as somatic control stimuli. Per protocol results were analyzed. Results. Of 14 randomized patients, 12 were treated with AZD1386. In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [-3%, 95% confidence interval (CI), -22;20%], distension (-11%, 95% CI, -28;10%), or electrical current (6%, 95% CI, -10;25%). Mean cutaneous heat tolerance increased by 4.9°C (95% CI, 3.7;6.2°C). AZD1386 increased the maximum body temperature by a mean of 0.59°C (95% CI, 0.40-0.79°C), normalizing within 4 h. Conclusions. AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response, whereas it increased cutaneous heat tolerance. TRPV1 does not play a major role in heat-, mechanically and electrically evoked esophageal pain in these patients. ClinicalTrials.gov identifier: D9127C00002.
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| 3. |
- Amanullah, Rahman, et al.
(author)
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Diversity in extinction laws of Type Ia supernovae measured between 0.2 and 2 μm
- 2015
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 453:3, s. 3300-3328
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Journal article (peer-reviewed)abstract
- We present ultraviolet (UV) observations of six nearby Type Ia supernovae (SNe Ia) obtained with the Hubble Space Telescope, three of which were also observed in the near-IR (NIR) with Wide-Field Camera 3. UV observations with the Swift satellite, as well as ground-based optical and NIR data provide complementary information. The combined data set covers the wavelength range 0.2-2 mu m. By also including archival data of SN 2014J, we analyse a sample spanning observed colour excesses up to E(B - V) = 1.4 mag. We study the wavelength-dependent extinction of each individual SN and find a diversity of reddening laws when characterized by the total-to-selective extinction R-V. In particular, we note that for the two SNe with E(B - V) greater than or similar to 1 mag, for which the colour excess is dominated by dust extinction, we find R-V = 1.4 +/- 0.1 and R-V = 2.8 +/- 0.1. Adding UV photometry reduces the uncertainty of fitted R-V by similar to 50 per cent allowing us to also measure R-V of individual low-extinction objects which point to a similar diversity, currently not accounted for in the analyses when SNe Ia are used for studying the expansion history of the Universe.
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| 4. |
- Andell, Pontus, et al.
(author)
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Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone
- 2017
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In: Circulation. Cardiovascular Interventions. - : Lippincott Williams & Wilkins. - 1941-7640 .- 1941-7632. ; 10:5
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Journal article (peer-reviewed)abstract
- Background: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study.Methods and Results: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80).Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.
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| 5. |
- Aneheim, Emma, 1982, et al.
(author)
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Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates
- 2016
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In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1520-4812 .- 1043-1802. ; 27:3, s. 688-97
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Journal article (peer-reviewed)abstract
- Effective treatment of metastasis is a great challenge in the treatment of different types of cancers. Targeted alpha therapy utilizes the short tissue range (50-100 μm) of α particles, making the method suitable for treatment of disseminated occult cancers in the form of microtumors or even single cancer cells. A promising radioactive nuclide for this type of therapy is astatine-211. Astatine-211 attached to tumor-specific antibodies as carrier molecules is a system currently under investigation for use in targeted alpha therapy. In the common radiolabeling procedure, astatine is coupled to the antibody arbitrarily on lysine residues. By instead coupling astatine to disulfide bridges in the antibody structure, the immunoreactivity of the antibody conjugates could possibly be increased. Here, the disulfide-based conjugation was performed using a new coupling reagent, maleimidoethyl 3-(trimethylstannyl)benzamide (MSB), and evaluated for chemical stability in vitro. The immunoconjugates were subsequently astatinated, resulting in both high radiochemical yield and high specific activity. The MSB-conjugate was shown to be stable with a long shelf life prior to the astatination. In a comparison of the in vivo distribution of the new immunoconjugate with other tin-based immunoconjugates in tumor-bearing mice, the MSB conjugation method was found to be a viable option for successful astatine labeling of different monoclonal antibodies.
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| 6. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 7. |
- Bergman, Sofia, et al.
(author)
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Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors : a VALIDATE-SWEDEHEART Substudy
- 2021
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In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:18
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Journal article (peer-reviewed)abstract
- Background: The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications.Methods and Results: The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P<0.001).Conclusions: IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.
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| 8. |
- Callesen, Katrine T., et al.
(author)
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Characterization of Mast Cells from Healthy and Varicose Human Saphenous Vein
- 2022
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:5
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Journal article (peer-reviewed)abstract
- Mast cells (MCs) are distributed in tissues throughout the body and are highly involved in many physiological and pathophysiological processes. The potential and involvement of different MC phenotypes are still not well understood. MCs are present in blood vessel walls, but their specific phenotypic features are unknown. We aimed at characterizing MCs from human saphenous veins for localization, mediator content, and receptor expression. This was done in MCs from both healthy and varicose human saphenous veins (hSV and vSV, respectively). For both vSV and hSV, we found that vein MCs are mainly present in the tunica adventitia (99% MCs in adventitia) and that the population consists of both MCT and MCTC phenotypes (vSV: 55% MCT, hSV: 64% MCT). The vein MCs contained high levels of histamine (vSV: 27 pg/MC, hSV: 55 pg/MC) and tryptase (vSV: 98 pg/MC, hSV: 111 pg/MC), indicating a strong potential for regulatory effects on blood vessels. The receptor expression of FcɛRI, MRGPRX2, PTAFR, C3aR, and C5aR was found, even though the percentage of positive cells differed between vSV and hSV MCs. We conclude that vein MCs from the blood vessel wall have a high potential to affect the tissue around them.
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| 9. |
- Castro-Espin, Carlota, et al.
(author)
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Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis : results from a cohort study
- 2023
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In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 128, s. 1301-1310
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Journal article (peer-reviewed)abstract
- Background: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival.Methods: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.Results: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality.Conclusions: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.
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| 10. |
- Castro-Tirado, A. J., et al.
(author)
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GRB 030227 : The first multiwavelength afterglow of an INTEGRAL GRB
- 2003
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 411:1, s. 315-319
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Journal article (peer-reviewed)abstract
- We present multiwavelength observations of a gamma-ray burst detected byINTEGRAL (GRB 030227) between 5.3 hours and ~ 1.7days after the event. Here we report the discovery of a dim opticalafterglow (OA) that would not have been detected by many previoussearches due to its faintess (R ~ 23). This OA was seen to declinefollowing a power law decay with index alpha R = -0.95 +/-0.16. The spectral index beta_ opt/NIR yielded -1.25 +/- 0.14. Thesevalues may be explained by a relativistic expansion of a fireball (withp = 2.0) in the cooling regime. We also find evidence for inverseCompton scattering in X-rays.Based on observations with INTEGRAL, an ESA project with instruments andscience data centre funded by ESA member states (especially the PIcountries: Denmark, France, Germany, Italy, Switzerland, Spain), CzechRepublic and Poland, and with the participation of Russia and the USA.Also partially based on observations collected by the Gamma-Ray BurstCollaboration at ESO (GRACE) at the European Southern Observatory, Chile(ESO Large Programme 165.H-0464).
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