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1.	Björkman, Kristoffer, et al. (författare) Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia 2022 Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9). Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
2.	Lewerin, Catharina, 1961, et al. (författare) Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden. 2014 Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140 Tidskriftsartikel (refereegranskat)abstract In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
3.	Bin Kaderi, Mohamed Arifin, 1978- (författare) Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the GNAS1, BCL2 and MDM2 genes and the RNA expression levels of the LPL, ZAP70, TCL1, CLLU1 and MCL1 genes were suggested as novel prognostic markers in CLL. In papers I-III, we performed genotyping analyses of the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL. In paper IV, we measured the RNA expression levels of LPL, ZAP70, TCL1, CLLU1 and MCL1 in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except MCL1, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for LPL and CLLU1 expression. Among the RNA-based markers, multivariate analysis revealed LPL expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results. In summary, data from papers I-III could not verify the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that LPL expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize LPL quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.
4.	Lundin, Anna-Carin (författare) Tendinosis in Trigger Finger 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
5.	Norberg, Maria, 1976- (författare) In Vitro Drug Sensitivity and Apoptosis in Chronic Lymphocytic Leukemia 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy displaying varying clinical outcome, where molecular markers today can divide patients into prognostic subgroups. Despite the introduction of new agents for treatment, remissions are usually not sustained in CLL and resistance towards treatment can partly be explained by aberrant apoptosis. The aim of this thesis was to find new drugs for CLL patients resistant to conventional therapy and to analyze genes involved in apoptosis within different prognostic subgroups. In paper I-II, the in vitro activity of substances was investigated using the fluorometric microculture cytotoxicity assay (FMCA). When evaluating rapamycin (paper I), an inhibitor of mTOR, in 97 tumor samples from different entities, CLL was found to be one of the most sensitive tumor types. Combination experiments on patient CLL cells indicated that rapamycin acted synergistically with the CLL drugs vincristine and chlorambucil. An investigation of 20 anti-cancer agents in cells from 40 CLL patients (paper II) revealed that prednisolone and rolipram displayed high activity in poor-prognostic patients, in particular IGHV unmutated CLL. Furthermore, when used in combination these agents were found to produce a synergistic effect. In paper III, the anti-apoptotic BCL2 family member BFL1 was evaluated in 37 CLL cases. Levels of BFL1 were higher in fludarabine-resistant patients compared to fludarabine-sensitive patients. In addition, the high expression of BFL1 inversely correlated to fludarabine-induced apoptosis in CLL cells. A single nucleotide polymorphism in the anti-apoptotic BCL2 gene (-938C>A) has been suggested as a novel poor-prognostic marker in CLL. In paper IV, we investigated this BCL2 polymorphism in 268 CLL patients and correlated genotypes to clinical data. However, no association could be confirmed between this polymorphism and clinical outcome or established prognostic markers. In conclusion, this thesis has shown that rapamycin is a potential drug for treatment in CLL. Furthermore, prednisolone and rolipram were identified as interesting candidates for treatment of poor-prognostic patients. Finally, the anti-apoptotic protein BFL1 may contribute to chemoresistance and hence represents a potential therapeutic target in CLL, whereas from our data, the BCL2 -938C>A polymorphism does not appear to have any prognostic significance.
6.	Lindgren, Marie, 1971, et al. (författare) Survival and risk of vascular complications in myelofibrosis—A population-based study from the Swedish MPN group 2022 Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 109:4, s. 336-342 Tidskriftsartikel (refereegranskat)abstract Objective: To gain knowledge of underlying risk factors for vascular complications and their impact on life expectancy in myelofibrosis. Methods: From a cohort of 392 myelofibrosis patients registered in the Swedish MPN registry 58 patients with vascular complications during follow-up were identified. Patients with vascular complications were compared with both 1:1 matched controls and the entire myelofibrosis cohort to explore potential risk factors for vascular complications and their impact on survival. Results: Incidence of vascular complications was 2.8 events per 100 patient-years and the majority of complications were thrombotic. Patients with complications were significantly older and had lower hemoglobin when compared to the entire cohort. In the case–control analysis, no significant risk factor differences were observed. The major cause of death was vascular complications and median survival was significantly impaired in patients with vascular complications (48 months) compared to controls (92 months). Inferior survival in patients with vascular complications was found to be dependent on IPSS risk category in a Cox regression model. Conclusion: Vascular complications have a considerable impact on survival in MF. At diagnosis, risk assessment by IPSS does not only predict survival but is also associated with the risk of vascular complications.
7.	Slind Olsen, Renate (författare) Circulating and genetic factors in colorectal cancer : Potential factors for establishing prognosis? 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression.In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis.The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment.To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment.The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation.In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.
8.	Halldórsdóttir, Anna Margrét, 1973- (författare) Genetic and Epigenetic Profiling of Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) both belong to the group of mature B-cell malignancies. However, MCL is typically clinically aggressive while the clinical course of CLL varies. CLL can be divided into prognostic subgroups based on IGHV mutational status and into multiple subsets based on closely homologous (stereotyped) B-cell receptors. In paper I we investigated 31 MCL cases using high-density 250K single-nucleotide polymorphism arrays and gene expression arrays. Although most copy-number aberrations (CNAs) were previously reported in MCL, a novel deletion was identified at 20q (16%) containing the candidate tumor suppressor gene ZFP64. A high proliferation gene expression signature was associated with poor prognosis, large CNAs, 7p gains and 9q losses. Losses at 1p/8p/13q/17p were associated with increased genomic complexity. In paper II we sequenced exons 4 to 8 of the TP53 gene in 119 MCL cases. 17p copy-number status was known from previous studies or determined by real-time quantitative polymerase chain reaction. TP53 mutations were detected in 14% of cases and were strongly associated with poor survival while 17p deletions were more common (32%) but did not predict survival. In papers III and IV we applied high-resolution genomic 27K methylation arrays to 20 MCL and 39 CLL samples. In paper III MCL displayed a homogenous methylation profile without correlation with the proliferation signature whereas MCL was clearly separated from CLL. Gene ontology analysis revealed enrichment of developmental genes, in particular homeobox transcription factor genes, among targets methylated in MCL. In paper IV we compared three different stereotyped CLL subsets: #1 (IGHV unmutated), #2 (IGHV3-21) and #4 (IGHV mutated). Many genes were differentially methylated between each two subsets and immune response genes (e.g. CD80 and CD86) were enriched among genes methylated in subset #1 but not in subsets #2/#4.In summary, CNAs were frequent and not random in MCL. Specific CNAs correlated with a high proliferation gene expression signature or genomic complexity. TP53 mutations predicted short survival whereas 17p deletions did not. A high proliferation signature was not associated with differential DNA methylation in MCL, which demonstrated a homogeneous methylation pattern. In contrast, genomic methylation patterns differed between MCL and CLL and between stereotyped CLL subsets.
9.	Walladbegi, Java, et al. (författare) Innovative intraoral cooling device better tolerated and equally effective as ice cooling. 2017 Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 80:5, s. 965-972 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Most of the patients who receive myeloablative therapy prior to stem cell transplantation develop oral mucositis (OM). This adverse reaction manifests as oral mucosal erythema and ulcerations and may require high doses of morphine for pain alleviation. OM may also interfere with food intake and result in weight loss, a need for parenteral nutrition, and impaired quality of life. To date, there have been very few studies of evidence-based interventions for the prevention of OM. Cryotherapy, using ice chips, has been shown to reduce in an efficient manner the severity and extent of OM, although clinical applications are still limited due to several shortcomings, such as adverse tooth sensations, problems with infectious organisms in the water, nausea, and uneven cooling of the oral mucosa. The present proof-of-concept study was conducted to compare the tolerability, temperature reduction, and cooling distribution profiles of an intra-oral cooling device and ice chips in healthy volunteers who did not receive myeloablative treatment, and therefore, did not experience the symptoms of OM.METHODS: Twenty healthy volunteers used the cooling device and ice chips for a maximum of 60 min each, using a cross-over design. The baseline and final temperatures were measured at eight intra-oral locations using an infra-red thermographic camera. The thermographic images were analysed using two digital software packages. A questionnaire was used to assess the tolerability levels of the two interventions.RESULTS: The intra-oral cooling device was significantly better tolerated than the ice-chips (p = 0.0118). The two interventions were equally effective regarding temperature reduction and cooling distribution.CONCLUSIONS: The intra-oral cooling device shows superior tolerability in healthy volunteers. Furthermore, this study shows that temperature reduction and cooling distribution are achieved equally well using either method.
10.	Hofving, Tobias, 1989, et al. (författare) 177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition 2019 Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 26:4, s. 437-449 Tidskriftsartikel (refereegranskat)abstract Lu-177-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The Lu-177-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the Lu-177-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate < 3.2 x 10(-11)). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of Lu-177-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of Lu-177-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of Lu-177-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.
11.	Juliusson, Gunnar, et al. (författare) Age and acute myeloid leukemia : real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry 2009 Ingår i: Blood. - Washington D.C. : American Society of Haematology. - 0006-4971 .- 1528-0020. ; 113:18, s. 4179-4187 Tidskriftsartikel (refereegranskat)abstract Acute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (nonacute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.
12.	Wennergren, Göran, 1947 (författare) Medicinarminnen som fängslar 2019 Ingår i: Läkartidningen. - 0023-7205. ; 116 Recension (övrigt vetenskapligt/konstnärligt)
13.	Toporski, Jacek, et al. (författare) High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. 2009 Ingår i: Biology of Blood and Marrow Transplantation. - : Elsevier BV. - 1083-8791. ; 15:9, s. 1077-1085 Tidskriftsartikel (refereegranskat)abstract We evaluated the feasibility and efficacy of using high-dose iodine-131-metaiodobenzylguanidine ((131)I-MIBG) followed by reduced-intensity conditioning (RIC) and transplantation of T cell-depleted haploidentical peripheral blood stem cells (designated haplo-SCT) to treat relapsing/refractory neuroblastoma (RRNB). Five RRNB patients were enrolled: 4 with relapse (3 after autologous SCT) and 1 with induction therapy failure. The preparative regimen included high-dose (131)I-MIBG on day -20, followed by fludarabine (Flu), thiotepa, and melphalan (Mel) from day -8 to -1. Granulocyte-colony stimulating factor (G-CSF)-mobilized, T cell-depleted haploidentical paternal stem cells were infused on day 0 together with cultured donor mesenchymal stem cells. A single dose of rituximab was given on day +1. After cessation of short immunosuppression (mycophenolate, OKT3), 4 children received donor lymphocyte infusion (DLI). (131)I-MIBG infusion and RIC were well tolerated. All patients engrafted. No primary acute graft-versus-host disease (aGVHD) was observed. Four children developed aGVHD after DLI and were successfully treated. Analysis of immunologic recovery showed fast reappearance of potentially immunocompetent natural killer (NK) and T cells, which might have acted as effector cells responsible for the graft-versus-tumor (GVT) effect. Two children are alive and well, with no evidence of disease 40 and 42 months after transplantation. One patient experienced late progression with new bone lesions (sternum) 38 months after haplo-SCT, and is being treated with local irradiation and reinstituted DLI. One patient rejected the graft, was rescued with autologous backup, and died of progressive disease 5 months after transplantation. Another child relapsed 7 months after transplantation and died 5 months later. High-dose (131)I-MIBG followed by RIC and haplo-SCT for RRNB is feasible and promising, because 2 of 5 children on that regimen achieved long-lasting remission. Further studies are needed to evaluate targeted therapy and immune-mediated tumor control in high-risk neuroblastoma.
14.	Wilhelmsson, Mari, et al. (författare) Hospitalizations in long-term survivors of childhood AML treated with allogeneic HCT—An Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study 2021 Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 96 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
15.	Maasfeh, Lujain, et al. (författare) Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission 2021 Ingår i: Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 12:4, s. 1415-1432 Tidskriftsartikel (refereegranskat)abstract BACKGROUND & AIMS: Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. METHODS: Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. RESULTS: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4(+) T-cell activation and interferon gamma secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. CONCLUSIONS: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.
16.	Robinson, Yohan, 1977, et al. (författare) Intravascular hemolysis and mean red blood cell age in athletes. 2006 Ingår i: Medicine and science in sports and exercise. - : Ovid Technologies (Wolters Kluwer Health). - 0195-9131 .- 1530-0315. ; 38:3, s. 480-3 Tidskriftsartikel (refereegranskat)abstract Since the observation that mechanical stress causes red blood cell (RBC) destruction, foot-strike hemolysis has been used to explain sports anemia and RBC rejuvenation in athletes. Recently gained knowledge questions the importance of mechanical RBC trauma on RBC hemolysis in athletes.Male athletes (N = 90) and untrained male controls (N = 58) were investigated for aerobic performance, hematological parameters, serum erythropoietin concentration (EPO), soluble transferrin receptor concentration (sTFR), and erythrocyte aspartate aminotransferase activity (eAST).On hard floor running disciplines (HFR, N = 26, short- and long-distance runners, triathletes) showed a lower eAST (P < 0.001) and thus no younger RBC population than not on hard floor running athletes (NHFR, N = 64, cyclists, soccer players, others) or the untrained control group (N = 58). HFR had higher but still normal EPO (P < 0.01) and no higher sTFR.Because intravascular hemolysis occurs in swimmers, cyclists, and runners, and mean RBC age is not reduced in runners, mechanisms other than foot-strike hemolysis have to be considered as well. Possible reasons are intramuscular destruction, osmotic stress, and membrane lipid peroxidation caused by free radicals released by activated leukocytes. Intravascular hemolysis can even be regarded as physiological means to provide heme and proteins for muscle growth.
17.	Deribe, Leul, et al. (författare) Stress and coping strategies among parents of children with cancer at Tikur Anbessa Specialized Hospital paediatric oncology unit, Ethiopia: a phenomenological study 2023 Ingår i: BMJ. British Medical Journal. - : BMJ. - 0959-8146. ; 13:e065090, s. 1-13 Tidskriftsartikel (refereegranskat)abstract Objective This study explores sources of stress, conditions that help reduce stress levels and coping strategies among parents of children with cancer receiving chemotherapy at Tikur Anbessa Specialized Hospital (TASH) in Ethiopia. Design A qualitative phenomenological approach was used. Setting Parents of children receiving chemotherapy at the TASH paediatric oncology unit. Participants Fifteen semistructured in-depth interviews were conducted with nine mothers and six fathers of children with cancer from November 2020 to January 2021. Results Sources of stress related to child’s health condition as the severity of the child’s illness, fear of treatment side effects and loss of body parts were identified. Parents mentioned experiencing stress arising from limited access to health facilities, long waiting times, prolonged hospital stays, lack of chemotherapy drugs, and limited or inadequate information about their child’s disease condition and treatment. Other sources of stress were insufficient social support, stigmatisation of cancer and financial problems. Conditions decreasing parents’ stress included positive changes in the child’s health, receiving cancer treatment and access to drugs. Receiving counselling from healthcare providers, getting social support and knowing someone who had a positive treatment outcome also helped reduce stress. Coping strategies used by parents were religious practices including prayer, crying, accepting the child’s condition, denial and communication with health providers. Conclusion The main causes of stress identified by parents of children with cancer in Ethiopia were the severity of their child’s illness, expectations of poor treatment outcomes, unavailability of cancer treatment services and lack of social/financial support. Measures that should be considered to reduce parents’ stress include providing psycho-oncological care for parents and improving the counselling available to parents concerning the nature of the child’s illness, its treatment, diagnostic procedures and treatment side effects. It may also be helpful to establish and strengthen family support groups and parent-to-parent communication, improve the availability of chemotherapy drugs and offer more education on coping strategies.
18.	Bryl-Górecka, Paulina, et al. (författare) Bilberry Supplementation after Myocardial Infarction Decreases Microvesicles in Blood and Affects Endothelial Vesiculation 2020 Ingår i: Molecular Nutrition & Food Research. - : Wiley-VCH Verlagsgesellschaft. - 1613-4125 .- 1613-4133. ; 64:20 Tidskriftsartikel (refereegranskat)abstract Scope: Diet rich in bilberries is considered cardioprotective, but the mechanisms of action are poorly understood. Cardiovascular disease is characterized by increased proatherogenic status and high levels of circulating microvesicles (MVs). In an open-label study patients with myocardial infarction receive an 8 week dietary supplementation with bilberry extract (BE). The effect of BE on patient MV levels and its influence on endothelial vesiculation in vitro is investigated.Methods and results: MVs are captured with acoustic trapping and platelet-derived MVs (PMVs), as well as endothelial-derived MVs (EMVs) are quantified with flow cytometry. The in vitro effect of BE on endothelial extracellular vesicle (EV) release is examined using endothelial cells and calcein staining. The mechanisms of BE influence on vesiculation pathways are studied by Western blot and qRT-PCR. Supplementation with BE decreased both PMVs and EMVs. Furthermore, BE reduced endothelial EV release, Akt phosphorylation, and vesiculation-related gene transcription. It also protects the cells from P2X(7)-induced EV release and increase in vesiculation-related gene expression.Conclusion: BE supplementation improves the MV profile in patient blood and reduces endothelial vesiculation through several molecular mechanisms related to the P2X(7)receptor. The findings provide new insight into the cardioprotective effects of bilberries.
19.	Einarsdottir, Sigrun, et al. (författare) Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity. 2022 Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730 Tidskriftsartikel (refereegranskat)abstract Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
20.	Geisler, Christian H., et al. (författare) The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT) 2010 Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:8, s. 1530-1533 Tidskriftsartikel (refereegranskat)abstract Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPI(B) (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPI(B) is feasible.
21.	Hjalgrim, Henrik, et al. (författare) HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma 2010 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:14, s. 6400-6405 Tidskriftsartikel (refereegranskat)abstract A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A01 and HLA-A02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60-2.88] were associated with increased and HLA-A02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A01 and HLA-A02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV-related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV-related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL.
22.	Li, Xiangyu, et al. (författare) Classification of clear cell renal cell carcinoma based on PKM alternative splicing 2020 Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2 Tidskriftsartikel (refereegranskat)abstract Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
23.	Singh, Sukhi, 1990, et al. (författare) Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers 2019 Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 119:5, s. 735-743 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo.METHODS: Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step.RESULTS: = 0.007).CONCLUSION: Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT03441412.
24.	Kaderi, Mohd Arifin, et al. (författare) LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia 2011 Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:8, s. 1153-1160 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers.DESIGN AND METHODS:Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome.RESULTS:High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients.CONCLUSIONS:LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.
25.	Berntorp, Erik, et al. (författare) Centraliserad vård grundläggande i vårdprogram för blödarsjuka 1999 Ingår i: Läkartidningen. - 0023-7205. ; 96:15, s. 1849-1852 Tidskriftsartikel (refereegranskat)abstract Haemophilia is a rare and potentially life-threatening disease. In Sweden, with a population of approximately 8.5 million, about 350 people suffer from the more severe forms of haemophilia or von Willebrand disease. Meticulous management is important if the patients are to be spared chronic disability and serious treatment complications. The disease is lifelong and affects psychosocial aspects of life among patients and their families. With the help of a grant from the Swedish Board of Halth and Welfare, a care programme has been designed to guarantee Swedish haemophiliacs comparable and optimal care. The programme has been drawn up by representatives of the three haemophilia centres in Sweden (at University Hospital, Malmo, Sahlgrenska University Hospital, Gothenburg, and Karolinska Hospital, Stockholm) in co-operation with the World Federation of National Haemophilia Organisations. To ensure optimal individual application of the programme, individualised management strategies and patient information leaflets have been prepared.
26.	Gulati, Sasha, et al. (författare) Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study 2015 Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 4 Tidskriftsartikel (refereegranskat)abstract Background A wide range of antithrombotic medications can be used in the prevention and treatment of thrombosis. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage may have particularly devastating consequences with high morbidity, disability and mortality rates. The incidence and risks of intracranial hemorrhage in patients on antithrombotic treatments from regular clinical practice outside clinical trials remain largely unknown. It is not known if results from clinical trials can be extrapolated to everyday clinical practice. We will conduct a nationwide study to investigate the risks and incidence rates of intracranial hemorrhage in users oral antithrombotic drugs in Norway from 2008 through 2014. Methods and design The aim of this nationwide study is to investigate the incidence rates of intracranial hemorrhage requiring hospitalization in users of oral antithrombotic drugs. The study will be conducted within the approximately 4.7 million inhabitants of Norway from January 1st, 2008, to December 31st, 2014. Treatment and outcome data are obtained from the Norwegian patient registry and the Norwegian prescription database.
27.	Nozohoor, Shahab, et al. (författare) ABO blood group does not impact incidence or outcomes of surgery for acute type A aortic dissection 2020 Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 54:2, s. 124-129 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD).Design: A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality.Results: There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups.Conclusions: In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.
28.	Wändell, Per, et al. (författare) Association between antithrombotic treatment and hemorrhagic stroke in patients with atrial fibrillation—a cohort study in primary care 2017 Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 73:2, s. 215-221 Tidskriftsartikel (refereegranskat)abstract Objective: The objective of this study was to study the association between antithrombotic treatment and risk of hemorrhagic stroke (HS) in patients with atrial fibrillation (AF) treated in primary health care. Methods: Study population included all adults (n = 12,215) 45 years and older diagnosed with AF at 75 primary care centers in Sweden 2001–2007. Outcome was defined as a first hospital episode with a discharge episode of HS after the AF diagnosis. Association between HS and persistent treatment with antithrombotic agents (warfarin, acetylsalicylic acid (ASA), clopidogrel) was explored using Cox regression analysis, with hazard ratios (HRs) and 95 % CIs. Adjustment was made for age, socioeconomic status, and co-morbid cardiovascular conditions. Results: During a mean of 5.8 years (SD 2.4) of follow-up, 162 patients (1.3 %; 67 women and 95 men) with HS were recorded. The adjusted risk associated with persistent warfarin treatment compared to no antithrombotic treatment consistently showed no increased HS risk, HR for women 0.53 (95 % CI 0.23–1.27) and for men 0.55 (95 % CI 0.29–1.04); corresponding HRs for ASA were, for women, 0.45 (95 % CI 0.14–1.44) and, for men, 0.56 (95 % CI 0.24–1.29). Conclusions: In this clinical setting, we found no evidence pointing to an increased risk of HS with antithrombotic treatment.
29.	Ärnlöv, Johan, 1970-, et al. (författare) Serum Endostatin and Risk of Mortality in the Elderly Findings From 2 Community-Based Cohorts 2013 Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 33:11, s. 2689-2695 Tidskriftsartikel (refereegranskat)abstract Objective Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk. Approach and Results Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]). Conclusions High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.
30.	Berglund, Eva Caroline, et al. (författare) A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias 2022 Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9 Tidskriftsartikel (refereegranskat)abstract Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care. Clinical Trial Registration: [https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].
31.	Klein, Kim, et al. (författare) Characteristics and Outcomes of Pediatric Patients with t(16;16)-AML: Results of a Case Series By the International BFM Study Group 2017 Ingår i: Blood. 130 (Supplement 1), 2671.. - 0006-4971 .- 1528-0020. Konferensbidrag (refereegranskat)
32.	Petridou, Eleni Th., et al. (författare) In vitro fertilization and risk of childhood leukemia in Greece and Sweden 2012 Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 58:6, s. 930-936 Tidskriftsartikel (refereegranskat)abstract Background Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. Methods. The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1: 1 matched controls). The Swedish casecontrol study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. Results. Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR 2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR 1.77; 95% CI: 1.062.95) with no sufficient evidence of excess risk for other leukemias (OR 1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.4912.37) before age 2 years. Conclusions. IVF seems to be associated with increased risk of early onset ALL in the offspring.
33.	Robinson, Yohan, 1977, et al. (författare) Erythropoiesis in multiply injured patients. 2006 Ingår i: The Journal of trauma. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5282 .- 1529-8809. ; 61:5, s. 1285-91 Forskningsöversikt (refereegranskat)abstract Posttraumatic anemia in multiply injured patients is caused by hemorrhage, reduced red blood cell survival, and impaired erythropoiesis. Trauma-induced hyperinflammation causes impaired bone-marrow function by means of blunted erythropoietin (EPO) response, reduced iron availability, suppression and egress of erythroid progenitor cells. To treat posttraumatic anemia in severely injured patients, symptomatic therapy by blood transfusion is not sufficient. Furthermore, EPO, iron, and the use of red cell substitutes should be considered. The posttraumatic systemic inflammatory response syndrome (SIRS) induces posttraumatic anemia. Thus, a worsening of SIRS by a "second-hit" through blood transfusion ought to be avoided.
34.	Van De Munckhof, Anita, et al. (författare) Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase 2022 Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210 Tidskriftsartikel (refereegranskat)abstract Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization.Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization).Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed).Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
35.	Jönsson, Sofia, et al. (författare) [Hypereosinophilic syndrome--difficult-to-catch diagnosis. Targeted molecular diagnostics and treatment now possible thanks to gene discovery] : Hypereosinofilt syndrom--svårfångad diagnos. Genupptäckt ger nu möjlighet till riktad molekylär diagnostik och terapi. 2006 Ingår i: Läkartidningen. - 0023-7205. ; 103:36, s. 2556-9 Tidskriftsartikel (refereegranskat)
36.	Zainuddin, Norafiza, 1978-, et al. (författare) Quantitative evaluation of p16INK4a promoter methylation using pyrosequencing in de novo diffuse large B-cell lymphoma 2011 Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 35:4, s. 438-443 Tidskriftsartikel (refereegranskat)abstract The p16INK4a tumor suppressor gene can be inactivated by a variety of events including promoter hypermethylation. In diffuse large B-cell lymphoma (DLBCL), p16INK4a methylation has been associated with advanced disease stage and higher IPI. The prognostic impact of p16INK4a methylation in DLBCL remains unclear; however, it has been suggested to correlate with inferior outcome. To further investigate the clinical impact of p16INK4a methylation in DLBCL, promoter methylation of this gene was assessed quantitatively by pyrosequencing. Forty-two of 113 (37%) DLBCL patients with methylation level above 5% were categorized as methylated and subsequently divided into low, intermediate and high methylation categories. Overall, no association was shown between the extent of p16INK4a methylation and patients’ clinical characteristics, except disease stage (P=0.049). Moreover, we could not reveal any impact of p16INK4a methylation on lymphoma-specific survival. Although >25% of p16INK4a methylation correlated with a better progression-free survival (P=0.048), the significance of this finding, if any, needs to be further investigated. In conclusion, our finding questions the role of p16INK4a promoter methylation as a negative prognostic factor in DLBCL.
37.	Aurelius, Johan, 1980, et al. (författare) Anthracycline-based consolidation may determine outcome of post-consolidation immunotherapy in AML 2019 Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:11, s. 2771-2778 Tidskriftsartikel (refereegranskat)abstract Consolidation chemotherapy in acute myeloid leukemia (AML) aims at eradicating residual leukemic cells and mostly comprises high-dose cytarabine with or without the addition of anthracyclines, including daunorubicin. Immunogenic cell death (ICD) may contribute to the efficacy of anthracyclines in solid cancer, but the impact of ICD in AML is only partly explored. We assessed aspects of ICD, as reflected by calreticulin expression, in primary human AML blasts and observed induction of surface calreticulin upon exposure to daunorubicin but not to cytarabine. We next assessed immune phenotypes in AML patients in complete remission (CR), following consolidation chemotherapy with or without anthracyclines. These patients subsequently received immunotherapy with histamine dihydrochloride (HDC) and IL-2. Patients who had received anthracyclines for consolidation showed enhanced frequencies of CD8(+) T-EM cells in blood along with improved survival. We propose that the choice of consolidation therapy prior to AML immunotherapy may determine clinical outcome.
38.	Mansouri, Larry, et al. (författare) Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma 2016 Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. 2666-2670 Tidskriftsartikel (refereegranskat)abstract We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases, 27.3%). NFKBIE-deleted PMBL patients were more often therapy-refractory (P=.022) and displayed inferior outcome compared to wildtype patients (5-year survival: 59% vs. 78%; P=.034); however they appeared to benefit from radiotherapy (P=.022) and rituximab-containing regimens (P=.074). NFKBIEaberrations remained an independent factor in multivariate analysis (P=.003), also when restricting to immunochemotherapy-treated patients (P=.008). Whole-exome sequencing and gene expression-profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
39.	Simard, Julia F, et al. (författare) Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes 2013 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:11, s. 2659-2666 Tidskriftsartikel (refereegranskat)abstract Lifestyle factors and medical history are known to influence risk of non-Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all-cause and lymphoma-related mortality was assessed in a population-based cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma Etiology study in 1999-2002. Participants contributed time from NHL diagnosis until death or October 1, 2010, with virtually complete follow-up through linkage to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using stratified and multivariable-adjusted Cox regression models. During a median follow-up of 8.8 years, 670 patients (44%) died, with the majority of deaths attributed to lymphoma (86%). Current versus never smoking at diagnosis was associated with increased rate of all-cause death for all NHL (HR = 1.5, 1.2-1.8) and diffuse large B-cell lymphoma (HR = 1.8, 1.2-2.7). Low educational level (HR = 1.3, 1.1-1.7, <9 vs. >12 years) and NHL risk-associated autoimmune disease (HR = 1.4, 1.0-1.8) were associated with death for all NHL combined. However, evidence of an association with lymphoma-related death was limited. Body mass index, recent sunbathing and family history of hematopoietic malignancy were not consistently associated with death after NHL or its specific subtypes. These results add to the evidence that cigarette smoking, socioeconomic status and certain autoimmune diseases affect survival after NHL. Further investigations are needed to determine how these factors should be incorporated into clinical prognostic assessment.
40.	Sandström, Göran, et al. (författare) Helicobacter pylori Antibodies and Iron Deficiency in Female Adolescents. 2014 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11 Tidskriftsartikel (refereegranskat)abstract Iron deficiency (ID) is a common clinical problem worldwide, affecting primarily females. Helicobacter pylori (HP) infection has been shown to be associated with ID. The objective of this study was to define the prevalence of HP antibodies in female adolescents, and to find out if there was a correlation between HP infection and ID. The secondary aim was to study if regularly performed sporting activity, have any association to HP infection, in itself.
41.	Donnér, Isabella, et al. (författare) IL-6 as a possible marker of high risk neutropenia 2017 Ingår i: NOPHO Annual Meeting Abstracts, 19-23 May 2017 Stockholm, PO-16. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
42.	Zainuddin, Norafiza, 1978- (författare) Molecular Genetic Analysis in B-cell Lymphomas : A Focus on the p53 Pathway and p16INK4a 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The presence of TP53 mutations has been associated with inferior outcome in diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). In DLBCL, the impact of the TP53 codon 72 polymorphism and MDM2 SNP309 has not been clearly elucidated, whereas MDM2 SNP309 was suggested as a poor-prognostic marker in CLL. In addition, p16INK4a promoter hypermethylation has been implicated as a negative prognostic factor in DLBCL. The aim of this thesis was to further evaluate these molecular markers in well-characterised materials of DLBCL and CLL. In paper I, we investigated the prognostic role of TP53 mutation, codon 72 polymorphism and MDM2 SNP309 in DLBCL (n=102). The presence of TP53 mutations (12.7%) correlated with a poor lymphoma-specific and progression-free survival, and a particularly pronounced effect was observed in the germinal center subtype. Neither the MDM2 SNP309 nor the TP53 codon 72 polymorphism had an impact on age of onset or survival. In paper II, we applied pyrosequencing to measure the level of p16INK4a methylation in DLBCL (n=113). Thirty-seven percent of cases displayed p16INK4a methylation; however, no clear association could be observed between degree of methylation and clinical characteristics or lymphoma-specific survival. In papers III–IV, we investigated the prognostic role of MDM2 SNP309 (n=418) and TP53 mutation (n=268) in CLL. No correlation was observed between any particular MDM2 SNP309 genotype and time to treatment and overall survival. Furthermore, no association was found between the different MDM2 SNP309 genotypes and established CLL prognostic markers. TP53 mutations were detected in 3.7% of CLL patients; where the majority showed a concomitant 17p-deletion and only three carried TP53 mutations without 17p-deletion. We confirmed a significantly shorter overall survival and time to treatment in patients with both TP53 mutation and 17p-deletion. Altogether, our studies could confirm the negative prognostic impact of TP53 mutations in DLBCL, whereas MDM2 SNP309 and TP53 codon 72 polymorphisms appear to lack clinical relevance. We also question the role of p16INKa methylation as a poor-prognostic factor in DLBCL. Finally, the presence of TP53 mutation in CLL appears to be rare at disease onset and instead arise during disease progression.
43.	Dahlberg, Johan, 1988- (författare) Genetic Cartography at Massively Parallel Scale 2018 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Massively parallel sequencing (MPS) is revolutionizing genomics. In this work we use, refine, and develop new tools for the discipline.MPS has led to the discovery of multiple novel subtypes in Acute Lymphoblastic Leukemia (ALL). In Study I we screen for fusion genes in 134 pediatric ALL patients, including patients without an assigned subtype. In approximately 80% of these patients we detect novel or known fusion gene families, most of which display distinct methylation and expression patterns. This shows the potential for improvements in the clinical stratification of ALL. Large sample sizes are important to detect recurrent somatic variation. In Study II we investigate if a non-index overlapping pooling schema can be used to increase sample size and detect somatic variation. We designed a schema for 172 ALL samples and show that it is possible to use this method to call somatic variants.Around the globe there are many ongoing and completed genome projects. In Study III we sequenced the genome of 1000 Swedes to create a reference data set for the Swedish population. We identified more than 10 million variants that were not present in publicly available databases, highlighting the need for population-specific resources. Data, and the tools developed during this study, have been made publicly available as a resource for genomics in Sweden and abroad.The increased amount of sequencing data has created a greater need for automation. In Study IV we present Arteria, a computational automation system for sequencing core facilities. This system has been adopted by multiple facilities and has been used to analyze thousands of samples. In Study V we developed CheckQC, a program that provides automated quality control of Illumina sequencing runs. These tools make scaling up MPS less labour intensive, a key to unlocking the full future potential of genomics.The tools, and data presented here are a valuable contribution to the scientific community. Collectively they showcase the power of MPS and genomics to bring about new knowledge of human health and disease.
44.	Hedbrant, Johan, 1959-, et al. (författare) Ny mätmetod för käkmuskulaturen kan finna orsaken till tinnitus : Slutrapport Nutek 92-11904 1997 Rapport (övrigt vetenskapligt/konstnärligt)abstract Tinnitus är en åkomma som i lindrigare eller allvarligare former drabbar 17% av västvärldens befolkning. Ca 85 000 svenskar har tinnitus på invalidiserande nivå. Förutom mänskligt lidande orsakar tinnitus samhällskostnader på ca 1.5 miljard kr årligen. Orsaken är till största delen okänd.Vissa tecken tyder på ett samband mellan tinnitus och funktionsstörning i en käkmuskel. Några olika icke–invasiva metoder för mätning av muskelstörning i M Pterygoideus Lateralis har utvärderas. Två av dessa är intressanta för fortsatta studier.Termografi användes för att diagnosticera muskelstörningar på ytligt liggande muskler. Vi såg åtskilliga varma områden på ytliga käk– och nackmuskler på de patienter som hade käkledsstörningar, samt möjligen tecken på onormal värme från M Pterygoideus Lateralis. Mätförhållandena var dock ej ideala.En metod att mäta EMG med adaptiv noise cancelling provades. EMG från en ryggmuskel, stört av en “EKG–signal” från hjärtat användes. Metoden fungerade bra. Fortsatt metodutveckling på t.ex. ryggmuskler borde göras.
45.	Lovgren, M., et al. (författare) Bereaved Siblings' Advice to Health Care Professionals Working with Children with Cancer and their Families 2015 Ingår i: Pediatric Blood & Cancer. - 1545-5009 .- 1545-5017. ; 62:Suppl. 4, s. S349-S349 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
46.	Nordlund, Jessica (författare) Gene Expression and DNA Methylation in Acute Lymphoblastic Leukemia 2012 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Pediatric acute lymphoblastic leukemia (ALL) is the most common malignancy in children, which results from the malignant transformation of progenitor cells in the bone marrow into leukemic cells. The precise mechanisms for this transformation are not well defined, however recent studies suggest that aberrant regulation of gene expression or DNA methylation may play an important role. Hence, the aim of this thesis was to use novel methods to investigate genome-wide gene expression and DNA methylation patterns in a large collection of primary ALL cells from pediatric patients. With these studies, we aimed to increase the understanding of factors that regulate gene expression and DNA methylation in ALL.In the first study of the thesis we found that data obtained from genome-wide digital gene expression analysis enabled excellent cytogenetic subtype-specific classification of ALL cells and revealed new features of gene expression within the disease, such as prevalent antisense transcription and alternative polyadenylation. In the second study we used technology developed for large-scale single nucleotide polymorphism (SNP) genotyping for quantitative analysis of allele-specific gene expression (ASE), revealing widespread ASE in ALL cells. Analysis of DNA methylation in promoter regions of the genes displaying ASE using DNA-microarrays revealed frequent regulation of gene expression by DNA methylation. In the third study, using the same DNA methylation array, we identified differences in the DNA methylation patterns in ALL cells at diagnosis compared to healthy mononuclear cells from the bone marrow of the same children at remission. In the fourth study we measured the DNA methylation of >450,000 CpG sites across the genome in a large collection of ALL samples and non-leukemic control cells. We found that ALL cells displayed highly divergent DNA methylation patterns depending on their cytogenetic subtype and widespread regions of differential methylation were enriched for repressive histone marks. DNA methylation levels at distinct regions in the genome were substantially increased at relapse compared to matched cells from diagnosis.Collectively, the results presented in this thesis provide new insights into the patterns of gene expression and epigenetic changes in ALL and further increase our understanding of the development and progression of the disease, which will hopefully lead to better treatment options in the future.
47.	Sandström, Göran, et al. (författare) Increased Level of Serum Hepcidin in Female Adolescent Athletes. 2018 Ingår i: Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. - 1536-3724. ; 28:2, s. 180-183 Tidskriftsartikel (refereegranskat)abstract To determine the serum hepcidin concentration and standard hematological parameters in a group of female adolescent athletes, compared with a group of nonathlete females.A case-control study.A senior high school for athletes in Gothenburg, Sweden.All female athletes (70), at the school were offered to take part. Fifty-six athletes accepted. From a random sample of age-matched nonathletes, 71 students were recruited to the control group.Iron deficiency (ID) was determined by levels of serum iron, total iron-binding capacity, transferrin saturation (TS), and ferritin. Serum hepcidin was determined by a mass spectrometry method. All samples were taken at least 12 hours after training.The main result was the finding of a significantly elevated serum hepcidin level in the athlete group, 4.7 nmol/L compared with 3.3 nmol/L (P < 0.001) in the nonathlete group. In the athlete group, the serum iron concentration was significantly lower, 14.0 μmol/L compared with 17.6 μmol/L (P = 0.003) in the nonathlete group. No difference was found regarding TS, total iron binding capacity, and ferritin. There was no difference in the occurrence of ID or iron deficiency anaemia (IDA).These findings show an increase in serum hepcidin in a large group of female athletes. The elevated hepcidin levels may affect the iron balance of the athletes, adding to the traditional explanation of dietary intake/iron loss balance.
48.	Thomas, Owain, et al. (författare) Monitoring Low Molecular Weight Heparins at Therapeutic Levels: Dose-Responses of, and Correlations and Differences between aPTT, Anti-Factor Xa and Thrombin Generation Assays. 2015 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Low molecular weight heparins (LMWH's) are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.
49.	Boknäs, Niklas, et al. (författare) Response: Platelets do not generate activated factor XII-how inappropriate experimental models have led to misleading conclusions. 2014 Ingår i: Blood. - Wahington, USA : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:10, s. 1692-4 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
50.	Sadik, May, 1970, et al. (författare) Artificial Intelligence Increases the Agreement among Physicians Classifying Focal Skeleton/Bone Marrow Uptake in Hodgkin's Lymphoma Patients Staged with F-18 FDG PET/CT-a Retrospective Study 2023 Ingår i: Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1869-3474 .- 1869-3482. ; 57:2, s. 110-116 Tidskriftsartikel (refereegranskat)abstract Purpose Classification of focal skeleton/bone marrow uptake (BMU) can be challenging. The aim is to investigate whether an artificial intelligence-based method (AI), which highlights suspicious focal BMU, increases interobserver agreement among a group of physicians from different hospitals classifying Hodgkin's lymphoma (HL) patients staged with [F-18]FDG PET/CT. Methods Forty-eight patients staged with [F-18]FDG PET/CT at Sahlgenska University Hospital between 2017 and 2018 were reviewed twice, 6 months apart, regarding focal BMU. During the second time review, the 10 physicians also had access to AI-based advice regarding focal BMU. Results Each physician's classifications were pairwise compared with the classifications made by all the other physicians, resulting in 45 unique pairs of comparisons both without and with AI advice. The agreement between the physicians increased significantly when AI advice was available, which was measured as an increase in mean Kappa values from 0.51 (range 0.25-0.80) without AI advice to 0.61 (range 0.19-0.94) with AI advice (p = 0.005). The majority of the physicians agreed with the AI-based method in 40 (83%) of the 48 cases. Conclusion An AI-based method significantly increases interobserver agreement among physicians working at different hospitals by highlighting suspicious focal BMU in HL patients staged with [F-18]FDG PET/CT.

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