| 51. |
- Graves, J R, et al.
(författare)
-
Survivors of out of hospital cardiac arrest: their prognosis, longevity and functional status.
- 1997
-
Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 35:2, s. 117-21
-
Tidskriftsartikel (refereegranskat)abstract
- This paper reports, consistent with Utstein Style definitions, 13 years experience observing out-of-hospital cardiac arrest survivors' prognosis, longevity and functional status. We report for all patients, available outcome information for out-of-hospital cardiac arrest survivors in Göteborg Sweden between 1980 and 1993. Patients were followed for at least 1 year and some for over 14 years. From 1980 to 1993 Göteborg EMS treated 3754 out-of-hospital cardiac arrests. 9% (n = 324) were discharged from the hospital alive. Survivors' median age was 67 and 21% (n = 67) were women. Mortality rate was: 21% (n = 61) at 1 year; 56% (n = 78) by 5 years; and 82% (n = 32) by 10 years following the arrest. During the first 3 years, 16% (n = 46) experienced another cardiac arrest, 19% (n = 53) had an acute myocardial infraction and a total of 81% (n = 232) were rehospitalized for various conditions. 14% (n = 40) returned to previous employment, and 74% (n = 229) had retired before their arrest occurred. Cerebral performance categories (CPC) scores were: At hospital discharge N = 324; Data available for 320-1 = 53% (n = 171), 2 = 21% (n = 66), 3 = 24% (n = 77), 4 = 2% (n = 6). One year post arrest N = 263; Data available for 212-1 = 73% (n = 156), 2 = 9% (n = 18), 3 = 17% (n = 36), 4 = 1% (n = 2). Overall, 21% (n = 61) of cardiac arrest survivors died during the first year, and an additional 16% (n = 46) experienced another arrest. 73% of those patients who were still alive after 1 year returned to pre-arrest function.
|
|
| 52. |
- Hamadani, Mehdi, et al.
(författare)
-
Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation
- 2014
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1729-1736
-
Tidskriftsartikel (refereegranskat)abstract
- The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P < .001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
|
|
| 53. |
|
|
| 54. |
- Holmberg, Carl Jacob, et al.
(författare)
-
The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
- 2022
-
Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
|
|
| 55. |
|
|
| 56. |
|
|
| 57. |
|
|
| 58. |
- Kujala, M, et al.
(författare)
-
Expression of ion transport-associated proteins in human efferent and epididymal ducts
- 2007
-
Ingår i: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 133:4, s. 775-784
-
Tidskriftsartikel (refereegranskat)abstract
- Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na+/H+exchanger 3 (NHE3), the Cl−channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na+/H+exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted.
|
|
| 59. |
- Landin-Olsson, Mona, et al.
(författare)
-
Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
-
Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
|
|
| 60. |
|
|
| 61. |
- Lindman, Henrik, et al.
(författare)
-
A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1)
- 2018
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 94, s. 79-86
-
Tidskriftsartikel (refereegranskat)abstract
- Study aim: Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). Methods: Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). Patients with nadir leukopenia grade 0–2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75–90 mg/m2, C 900–1200 mg/m2) or fixed treatment with 6 standard FEC. Patients with grade 3–4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). Results: The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC (N = 524) or standard FEC (N = 528), whereas 401 patients with leukopenia grade 3–4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67–1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57–1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. Conclusions: The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment.
|
|
| 62. |
- Liu, RN, et al.
(författare)
-
HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5093-
-
Tidskriftsartikel (refereegranskat)abstract
- The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant forM. tuberculosiscontrol.Vhl cKOmice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
|
|
| 63. |
|
|
| 64. |
|
|
| 65. |
|
|
| 66. |
|
|
| 67. |
- McClune, Brian L., et al.
(författare)
-
Allotransplantation for Patients Age >= 40 Years with Non-Hodgkin Lymphoma : Encouraging Progression-Free Survival
- 2014
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:7, s. 960-968
-
Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age >= 40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age >= 65; P = .0008). Fewer patients aged >= 65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age >= 65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age >= 65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age >= 55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age >= 55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.
|
|
| 68. |
|
|
| 69. |
|
|
| 70. |
- Sanjeevi, Carani B., et al.
(författare)
-
The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
-
Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
|
|
| 71. |
- Sedimbi, S. K., et al.
(författare)
-
SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
-
Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
-
Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
|
|
| 72. |
- Simpkin, Andrew J., et al.
(författare)
-
Prostate-specific antigen patterns in US and European populations : comparison of six diverse cohorts
- 2016
-
Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:6, s. 911-918
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether there are differences in prostate-specific antigen (PSA) levels at diagnosis or changes in PSA levels between US and European populations of men with and without prostate cancer (PCa).SUBJECTS AND METHODS: We analysed repeated measures of PSA from six clinically and geographically diverse cohorts of men: two cohorts with PSA-detected PCa, two cohorts with clinically detected PCa and two cohorts without PCa. Using multilevel models, average PSA at diagnosis and PSA change over time were compared among study populations.RESULTS: The annual percentage PSA change of 4-5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7 ng/mL lower in a US cohort of men with PSA-detected PCa (95% confidence interval 1.3-2.0 ng/mL), compared with a UK cohort of men with PSA-detected PCa, but there was no evidence of a different rate of PSA change between these populations.CONCLUSION: We found that PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without PCa. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies.
|
|
| 73. |
|
|
| 74. |
- Sun, Chengjun, et al.
(författare)
-
CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
-
Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
|
|
| 75. |
|
|
| 76. |
- Uhlén, Fredrik, et al.
(författare)
-
Damage investigation on tungsten and diamond diffractive optics at a hard x-ray free-electron laser
- 2013
-
Ingår i: Optics Express. - : Optical Society America. - 1094-4087. ; 21:7, s. 8051-8061
-
Tidskriftsartikel (refereegranskat)abstract
- Focusing hard x-ray free-electron laser radiation with extremely high fluence sets stringent demands on the x-ray optics. Any material placed in an intense x-ray beam is at risk of being damaged. Therefore, it is crucial to find the damage thresholds for focusing optics. In this paper we report experimental results of exposing tungsten and diamond diffractive optics to a prefocused 8.2 keV free-electron laser beam in order to find damage threshold fluence levels. Tungsten nanostructures were damaged at fluence levels above 500 mJ/cm(2). The damage was of mechanical character, caused by thermal stress variations. Diamond nanostructures were affected at a fluence of 59 000 mJ/cm(2). For fluence levels above this, a significant graphitization process was initiated. Scanning Electron Microscopy (SEM) and mu-Raman analysis were used to analyze exposed nanostructures.
|
|
| 77. |
|
|
| 78. |
- Uttervall, K., et al.
(författare)
-
The Use of Novel Drugs Can Effectively Improve Response, Delay Relapse and Enhance Overall Survival in Multiple Myeloma Patients with Renal Impairment
- 2014
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor. Aim: To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response. Methods: The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m(2). Result: The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients. Conclusion: High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.
|
|
| 79. |
- Wallgren, Arne, 1940, et al.
(författare)
-
Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.
- 2003
-
Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 21:7, s. 1205-13
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.
|
|
| 80. |
|
|
| 81. |
|
|
| 82. |
|
|
| 83. |
- Andersson, M, et al.
(författare)
-
Isospin resolved double pion production in the reaction p+d -> He-3+2 pi
- 2000
-
Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 485:4, s. 327-333
-
Tidskriftsartikel (refereegranskat)abstract
- Neutral and charged two-pion production in p + d --> He-3 + 2 pi reactions has been studied at CELSIUS at a proton beam energy of 477 MeV. The total cross section for double pion production is 0.22 +/- 0.03 mu b. The ratio of the cross sections for the pr
|
|
| 84. |
|
|
| 85. |
- Andersson, M, et al.
(författare)
-
The exclusive p plus d -> He-3+2 pi reaction at CELSIUS
- 2000
-
Ingår i: ACTA PHYSICA POLONICA B. - : ACTA PHYSICA POLONICA B, JAGELLONIAN UNIV, INST PHYSICS. ; , s. 2123-2126
-
Konferensbidrag (refereegranskat)abstract
- Neutral and charged two-pion production in p + d --> He-3 --> 2 pi reactions has been studied at a proton beam energy of 477 MeV. The total cross section for double pion production is 0.22 +/- 0.03 mub. The ratio of the cross sections for the production o
|
|
| 86. |
- Aune, S, et al.
(författare)
-
Improvement in the hospital organisation of CPR training and outcome after cardiac arrest in Sweden during a 10-year period
- 2011
-
Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 82:4, s. 431-435
-
Tidskriftsartikel (refereegranskat)abstract
- Aim To describe (a) changes in the organisation of training in cardiopulmonary resuscitation (CPR) and the treatment of cardiac arrest in hospital in Sweden and (b) the clinical achievement, i.e. survival and cerebral function, among survivors after in-hospital cardiac arrest (IHCA) in Sweden. Methods Aspects of CPR training among health care providers (HCPs) and treatment of IHCA in Sweden were evaluated in 3 national surveys (1999, 2003 and 2008). Patients with IHCA are recorded in a National Register covering two thirds of Swedish hospitals. Results The proportion of hospitals with a CPR coordinator increased from 45% in 1999 to 93% in 2008. The majority of co-ordinators are nurses. The proportions of hospitals with local guidelines for acceptable delays from cardiac arrest to the start of CPR and defibrillation increased from 48% in 1999 to 88% in 2008. The proportion of hospitals using local defibrillation outside intensive care units prior to arrival of rescue team increased from 55% in 1999 to 86% in 2008. During the past 4 years in Sweden, survival to hospital discharge has been 29%. Among survivors, 93% have a cerebral performance category (CPC) score of I or II, indicating acceptable cerebral function. Conclusion During the last 10 years, there was a marked improvement in CPR training and treatment of IHCA in Sweden. During the past 4 years, survival after IHCA is high and the majority of survivors have acceptable cerebral function.
|
|
| 87. |
- Axelsson, Åsa B., 1955, et al.
(författare)
-
Factors surrounding cardiopulmonary resuscitation influencing bystanders' psychological reactions.
- 1998
-
Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 37:1, s. 13-20
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of Sweden's out-of-hospital cardiac arrests averages 10000 annually. Each year bystanders initiate cardiopulmonary resuscitation (CPR) approximately 2000 times prior to arrival of emergency medical service (EMS). The aim of this study was to identify factors influencing the bystanders psychological reactions to performing CPR. We mailed a questionnaire to all bystanders who reported performing CPR to the CPR Centre of Sweden from autumn 1992 to 1995. The study included 544 bystander reports. Nine factors were found to be associated with bystanders experience in a univariate analysis. Among these were victim outcome (p < 0.0001), CPR duration (p = 0.0009) and their experience of the attitude of the EMS personnel (p = 0.004). In a multivariate logistic regression model, lack of debriefing following the intervention (p = 0.0001) and fatal victim outcome (p = 0.03) were independent predictors of a negative bystander psychological reaction. The importance of having someone to talk to following an intervention and the EMS personnel concern for the rescuer should be emphasised. The goal should be that critical incident debriefing is available to every bystander following his or her CPR attempt.
|
|
| 88. |
|
|
| 89. |
|
|
| 90. |
|
|
| 91. |
|
|
| 92. |
|
|
| 93. |
|
|
| 94. |
- Bolin, Sara, 1988-, et al.
(författare)
-
Dormant SOX9-positive cells behind MYC-driven medulloblastoma recurrence
-
Tidskriftsartikel (refereegranskat)abstract
- Tumor recurrence is a slow biological process involving therapy resistance, immune escape, and metastasis and is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. By studying paired primary-recurrent patient samples and patient-derived xenografts we identified a significant accumulation of SOX9-positive cells in relapses and metastases. They exist as rare, quiescent cells in Group 3 and Group 4 patients that constitute two-thirds of medulloblastoma. To follow relapse at the single-cell level we developed an inducible dual Tet model of MYC-driven MB, where MYC can be directed from treatment-sensitive bulk cells to resistant, dormant SOX9-positive cells by doxycycline. SOX9 promoted immune es-cape, DNA repair suppression and was essential for recurrence. Tumor cell dormancy was non-hierarchical, migratory, and depended on MYC suppression by SOX9 to promote relapse. By using computational modeling and treatment we further showed how doxorubicin and MGMT inhibitors are specifically targeting relapsing cells.
|
|
| 95. |
- Borgenvik, Anna, 1987-, et al.
(författare)
-
Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
- 2022
-
Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 82:24, s. 4586-4603
-
Tidskriftsartikel (refereegranskat)abstract
- Relapse is the leading cause of death in patients with medulloblas-toma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.Significance: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
|
|
| 96. |
- Born, D. -P, et al.
(författare)
-
Circadian variation of salivary immunoglobin A, alpha-amylase activity and mood in response to repeated double-poling sprints in hypoxia
- 2016
-
Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 116:1, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess the circadian variations in salivary immunoglobin A (sIgA) and alpha-amylase activity (sAA), biomarkers of mucosal immune function, together with mood during 2 weeks of repeated sprint training in hypoxia (RSH) and normoxia (RSN). Methods: Over a 2-week period, 17 competitive cross-country skiers performed six training sessions, each consisting of four sets of five 10-s bouts of all-out double-poling under either normobaric hypoxia (FiO2: 13.8 %, 3000 m) or normoxia. The levels of sIgA and sAA activity and mood were determined five times during each of the first (T1) and sixth (T6) days of training, as well as during days preceding (baseline) and after the training intervention (follow-up). Results: With RSH, sIgA was higher on T6 than T1 (P = 0.049), and sAA was increased on days T1, T6, and during the follow-up (P < 0.01). With RSN, sIgA remained unchanged and sAA was elevated on day T1 only (P = 0.04). Similarly, the RSH group demonstrated reduced mood on days T1, T6, and during the follow-up, while mood was lowered only on T1 with RSN (P < 0.01). Conclusions: The circadian variation of sIgA and sAA activity, biomarkers of mucosal immune function, as well as mood were similar on the first day of training when repeated double-poling sprints were performed with or without hypoxia. Only with RSH did the levels of sIgA and sAA activity rise with time, becoming maximal after six training sessions, when mood was still lowered. Therefore, six sessions of RSH reduced mood, but did not impair mucosal immune function. © 2015, Springer-Verlag Berlin Heidelberg.
|
|
| 97. |
- Buervenich, Silvia, et al.
(författare)
-
A rare truncating mutation in ADH1C (G78Stop) shows significant association with Parkinson disease in a large international sample.
- 2005
-
Ingår i: Archives of neurology. - : American Medical Association (AMA). - 0003-9942. ; 62:1, s. 74-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. PATIENTS: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. RESULTS: The previously identified association with an ADH class IV allele remained significant (P<.02) in the extended Swedish study. Furthermore, in the international collaboration, the G78stop mutation in ADH1C was found in 22 (2.0%) of the PD patients but only in 6 controls (0.6%). This association was statistically significant (chi(2)(1) = 7.5; 2-sided P = .007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. CONCLUSION: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.
|
|
| 98. |
- Carlsson, Sigrid, 1982, et al.
(författare)
-
No excess mortality after prostate biopsy: results from the European Randomized Study of Screening for Prostate Cancer.
- 2011
-
Ingår i: BJU international. - 1464-410X. ; 107:12, s. 1912-1917
-
Tidskriftsartikel (refereegranskat)abstract
- Study Type - Harm (RCT)Level of Evidence1b OBJECTIVES: To assess possible excess mortality associated with prostate biopsy among screening participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC). SUBJECTS AND METHODS: From three centres in the ERSPC (Finland, The Netherlands and Sweden) 50194 screened men aged 50.2-78.4 years were prospectively followed. A cohort of 12959 first-time screening-positive men (i.e. with biopsy indication) was compared with another cohort of 37235 first-time screening-negative men. Overall mortality rates (i.e. other cause than prostate cancer mortality) were calculated and the 120-day and 1-year cumulative mortality were calculated by the Kaplan-Meier method, with a log-rank test for statistical significance. Incidence rate ratios (RR) and statistical significance were evaluated using Poisson regression analyses, adjusting for age, total PSA level, screening centre and whether a biopsy indication was present, or whether a biopsy was actually performed or not. RESULTS: There was no statistically significant difference in cumulative 120-day other cause mortality between the two groups of men: 0.24% (95% CI, 0.17-0.34) for screening-positive men vs 0.24% (95% CI, 0.20-0.30) for screening-negative men (P= 0.96). This implied no excess mortality for screening-positive men. Screening-positive men who were not biopsied (n= 1238) had a more than fourfold risk of other cause mortality during the first 120 days compared to screening-negative men: RR, 4.52 (95% CI, 2.63-7.74) (P < 0.001), adjusted for age, whereas men who were actually biopsied (n= 11721) had half the risk: RR, 0.41 (95% CI, 0.23-0.73) (P= 0.002), adjusted for age. Only 14/31 (45%) of the screening-positive men who died within 120 days were biopsied and none died as an obvious complication to the biopsy. CONCLUSIONS: Prostate biopsy is not associated with excess mortality and fatal complications appear to be very rare.
|
|
| 99. |
- Carter, H Ballentine, et al.
(författare)
-
Early detection of prostate cancer : AUA Guideline
- 2013
-
Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 190:2, s. 419-426
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.MATERIALS AND METHODS:A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).RESULTS:Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.CONCLUSIONS:The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.
|
|
| 100. |
- Cheng, Arthur J., et al.
(författare)
-
Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle
- 2017
-
Ingår i: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 595:24, s. 7413-7426
-
Tidskriftsartikel (refereegranskat)abstract
- Key points: We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of ˜ 38°C than when they were cooled to as low as 15°C, which suggested that recovery of exercise performance in humans is dependent on muscle temperature. Mechanisms underlying the temperature-dependent effect on recovery were studied in intact single mouse muscle fibres where we found that recovery of submaximal force and restoration of fatigue resistance was worsened by cooling (16-26°C) and improved by heating (36°C). Isolated whole mouse muscle experiments confirmed that cooling impaired muscle glycogen resynthesis. We conclude that skeletal muscle recovery from fatigue-induced by endurance exercise is impaired by cooling and improved by heating, due to changes in glycogen resynthesis rate.Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by 2 h recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca2+] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole flexor digitorum brevis muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.
|
|
