| 61. |
- Paulsson, Kajsa, et al.
(författare)
-
High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols.
- 2013
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 98:9, s. 1424-1432
-
Tidskriftsartikel (refereegranskat)abstract
- Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age was lower in the patients with 'classic' high hyperdiploidy than in those with translocation-positive high hyperdiploidy (P<0.001). Cases with triple trisomies (+4, +10, +17), comprising 50%, had higher modal numbers than the triple trisomy-negative cases (P<0.0001). The probabilities of event-free survival and overall survival were lower for those with white blood cell counts ≥50 x 109/L (P=0.017/P=0.009), ≥5% bone marrow blasts at day 29 (P=0.001/0.002), and for high risk patients (P<0.001/P=0.003), whereas event-free, but not overall, survival, was higher for cases with gains of chromosomes 4 (P<0.0001), 6 (P<0.003), 17 (P=0.010), 18 (P=0.049), and 22 (P=0.040), triple trisomies (P=0.002), and modal numbers >53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same patient subgroup characterized by a particularly favorable outcome.
|
|
| 62. |
- Peng, Xiang, et al.
(författare)
-
The neutrophil serine protease PR3 induces shape change of platelets via the Rho/Rho kinase and Ca2+ signaling pathways
- 2014
-
Ingår i: Thrombosis Research. - Oxon, United Kingdom : Elsevier. - 0049-3848 .- 1879-2472. ; 134:2, s. 418-425
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proteinase 3 (PR3) is released from neutrophil azurophilic granules and exerts complex effects on the inflammatory process. PR3 catalyzes the degradation of a number of macromolecules, but the consequences on blood cells are less well defined. In the present study, the effect of PR3 on human platelets was thoroughly investigated.Methods: The experiments were performed on washed platelets freshly isolated from blood donated by healthy human volunteers. Platelets shape change and aggregation was measured on a Chrono-Log aggregometer. The phosphorylated form of MYPT1 was visualized by immunostaining. Platelet activation was further evaluated by flow cytometry.Results: PR3 induced platelet shape change but not aggregation. Flow cytometry analysis showed that PR3 induced no P-selectin expression or binding of fibrinogen to the platelets, and it did not change the activation in response to PAR1- or PAR4-activating peptides or to thrombin. Furthermore, Fura-2 measurement and immuno-blotting analysis, respectively, revealed that PR3 stimulated small intracellular Ca2+ mobilization and Thr696-specific phosphorylation of the myosin phosphatase target subunit 1 (MYPT1). Separate treatment of platelets with the Rho/Rho kinase inhibitor Y-27632 and the intracellular Ca2+ chelator BAPTA/AM reduced the shape change induced by PR3 whereas concurrent treatment completely inhibited it.Conclusion: The data shows that the neutrophil protease PR3 is a direct modulator of human platelets and causes shape change through activation of the Rho/Rho kinase and Ca2+ signaling pathways. This finding highlights an additional mechanism in the complex interplay between neutrophils and platelets.
|
|
| 63. |
- Walinder, Göran, et al.
(författare)
-
Outcome and characteristics of non-measurable myeloma : A cohort study with population-based data from the Swedish Myeloma Registry
- 2020
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 104:5, s. 376-382
-
Tidskriftsartikel (refereegranskat)abstract
- Objective We describe survival in patients with oligo- and non-secretory multiple myeloma (MM). We refer to the whole group as non-measurable MM and compare it with secretory MM. Methods Oligo-secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non-secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio. Results Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008-2016 eligible for the study, 389 patients (9%) had non-measurable MM. Out of these, 253 patients (6%) had oligo-secretory and 136 (3%) had non-secretory MM. Median survival for secretory MM was 42.7 months, non-measurable MM 40.2 months, oligo-secretory MM 38.6 months, and non-secretory MM 44.6 months. Difference in overall observed survival was non-significant for all groups when compared with secretory MM. Within non-secretory MM, stem cell transplantation (SCT), 95% being auto-SCT, was significant for superior survival in multivariate analysis (HR 0.048. P = .0015). Conclusion In this population-based study, we found no difference in survival between oligo- or non-secretory MM when compared with secretory MM. SCT appears to be important also for patients with non-secretory disease.
|
|
| 64. |
- Danielsson, H., et al.
(författare)
-
Blood protein profiles related to preterm birth and retinopathy of prematurity
- 2022
-
Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 91:4, s. 937-946
-
Tidskriftsartikel (refereegranskat)abstract
- Background Nearly one in ten children is born preterm. The degree of immaturity is a determinant of the infant's health. Extremely preterm infants have higher morbidity and mortality than term infants. One disease affecting extremely preterm infants is retinopathy of prematurity (ROP), a multifactorial neurovascular disease that can lead to retinal detachment and blindness. The advances in omics technology have opened up possibilities to study protein expressions thoroughly with clinical accuracy, here used to increase the understanding of protein expression in relation to immaturity and ROP. Methods Longitudinal serum protein profiles the first months after birth in 14 extremely preterm infants were integrated with perinatal and ROP data. In total, 448 unique protein targets were analyzed using Proximity Extension Assays. Results We found 20 serum proteins associated with gestational age and/or ROP functioning within mainly angiogenesis, hematopoiesis, bone regulation, immune function, and lipid metabolism. Infants with severe ROP had persistent lower levels of several identified proteins during the first postnatal months. Conclusions The study contributes to the understanding of the relationship between longitudinal serum protein levels and immaturity and abnormal retinal neurovascular development. This is essential for understanding pathophysiological mechanisms and to optimize diagnosis, treatment and prevention for ROP. Impact Longitudinal protein profiles of 14 extremely preterm infants were analyzed using a novel multiplex protein analysis platform combined with perinatal data. Proteins associated with gestational age at birth and the neurovascular disease ROP were identified. Among infants with ROP, longitudinal levels of the identified proteins remained largely unchanged during the first postnatal months. The main functions of the proteins identified were angiogenesis, hematopoiesis, immune function, bone regulation, lipid metabolism, and central nervous system development. The study contributes to the understanding of longitudinal serum protein patterns related to gestational age and their association with abnormal retinal neuro-vascular development.
|
|
| 65. |
- Haider, Zahra, et al.
(författare)
-
An integrated transcriptome analysis in T-cell acute lymphoblastic leukemia links DNA methylation subgroups to dysregulated TAL1 and ANTP homeobox gene expression
- 2019
-
Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 8:1, s. 311-324
-
Tidskriftsartikel (refereegranskat)abstract
- Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.
|
|
| 66. |
- Haider, Zahra, 1988-
(författare)
-
DNA methylation signatures in precursor lymphoid neoplasms : with focus on clinical implications & the biology behind
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Precursor lymphoid neoplasms, namely acute lymphoblastic leukemias (ALL) and lymphoblastic lymphomas (LBL), are characterized by an aggressive proliferation of malignant progenitor B- or T-cells. To improve risk classification at diagnosis, better prognostic and treatment stratifying biomarkers are needed. Altered DNA methylation pattern is a hallmark of neoplastic transformation, and has been employed as a molecular prognostic and predictive marker in various cancers, including hematological malignancies. Our research group previously identified a CpG island methylator phenotype (CIMP) panel that classified pediatric T-ALL patients into prognostic subgroups.The aim of this thesis was to evaluate distinct DNA methylation signatures in precursor lymphoid neoplasms, and to validate the prognostic value of CIMP classification in separate patient cohorts. Additionally, the biological mechanisms underlying the distinct CIMP methylation signatures in these malignancies were investigated.The prognostic relevance of CIMP classification was validated in an independent Nordic cohort of pediatric T-ALL patients. Combination of CIMP status with minimal residual disease (MRD) status, could further dissect the high-risk MRD positive T-ALL patients into two CIMP subgroups with significantly distinct outcomes. Furthermore, CIMP classification at diagnosis was shown to predict overall survival in relapsed BCP-ALL patients. CIMP methylation signatures were also identified in T-LBL patients, indicating a broader relevance of CIMP based classification in lymphoid malignancies. Investigating the biology behind CIMP methylation signatures showed the association of CIMP status with the proliferative history of the leukemic cells. A differential transcriptomic analysis revealed a correlation of CIMP subgroups with known T-ALL drivers, as well as with novel genes in T-ALL biology. Finally, we identified distinct DNA methylation patterns and genetic aberrations in T-ALL and T-LBL that might contribute to the different clinical presentation of these two diseases. In conclusion, we validated the prognostic significance of CIMP methylation signature in precursor lymphoid malignancies and identified transcriptomic profiles that associated with the subgroups. DNA methylation is a strong candidate for further risk classification in lymphoid neoplasms and our findings can contribute to the identification of new potential targets for treatment.
|
|
| 67. |
|
|
| 68. |
- Holmqvist, Jacob, et al.
(författare)
-
Patterns and determinants of blood transfusion in intensive care in Sweden between 2010 and 2018: A nationwide, retrospective cohort study
- 2022
-
Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 62:6, s. 1188-1198
-
Tidskriftsartikel (refereegranskat)abstract
- Background Intensive care unit (ICU) patients are transfused with blood products for a number of reasons, from massive ongoing hemorrhage, to mild anemia following blood sampling, combined with bone marrow depression due to critical illness. There's a paucity of data on transfusions in ICUs and most studies are based on audits or surveys. The aim of this study was to provide a complete picture of ICU-related transfusions in Sweden. Methods We conducted a register based retrospective cohort study with data on all adult patient admissions from 82 of 84 Swedish ICUs between 2010 and 2018, as recorded in the Swedish Intensive Care Register. Transfusions were obtained from the SCANDAT-3 database. Descriptive statistics were computed, characterizing transfused and nontransfused patients. The distribution of blood use comparing different ICUs was investigated by computing the observed proportion of ICU stays with a transfusion, as well as the expected proportion. Results In 330,938 ICU episodes analyzed, at least one transfusion was administered for 106,062 (32%). For both red-cell units and plasma, the fraction of patients who were transfused decreased during the study period from 31.3% in 2010 to 24.6% in 2018 for red-cells, and from 16.6% in 2010 to 9.4% in 2018 for plasma. After adjusting for a range of factors, substantial variation in transfusion frequency remained, especially for plasma units. Conclusion Despite continuous decreases in utilization, transfusions remain common among Swedish ICU patients. There is considerable unexplained variation in transfusion rates. More research is needed to establish stronger critiera for when to transfuse ICU patients.
|
|
| 69. |
- Skagerlind, Malin, 1975-, et al.
(författare)
-
An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis
- 2018
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 74:3, s. 267-274
-
Tidskriftsartikel (refereegranskat)abstract
- Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.
|
|
| 70. |
- Bhaskar, S., et al.
(författare)
-
Delay of late-venous phase cortical vein filling in acute ischemic stroke patients: Associations with collateral status
- 2017
-
Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 37:2, s. 671-682
-
Tidskriftsartikel (refereegranskat)abstract
- Evaluation of the venous system may be useful in stroke prognostication and patient selection for acute intervention strategies. We report a novel phenomenon, delayed-late venous phase cortical vein filling, observed on dynamic computed tomography angiography obtained using multidetector computed tomography scanner, in acute ischemic stroke patients. The aim of this study was to examine the frequency of delayed-late venous phase cortical vein filling and assess its association to baseline collateral status. Dynamic computed tomography angiography images of acute ischemic stroke patients, being assessed for reperfusion therapy, were prospectively studied. Delayed-late venous phase cortical vein filling was defined by late venous phase opacification of cortical veins despite contrast clearance from contralateral cortical veins on dynamic computed tomography angiography. Time to peak of maximum arterial enhancement was recorded. A total of 117 patients (mean age = 70.6 +/- 13.3 years; males = 48%) with hemispheric ischemic stroke who underwent acute dynamic computed tomography angiography were included in the study. Overall, 56 (48%) demonstrated delayed-late venous phase cortical vein filling. Poor collateralization (OR = 13.50; 95% CI = (4.2, 43); p <= 0.0001) and longer time to peak of maximum arterial enhancement (OR = 3.2; 95% CI = (1.96, 5.3); p <= 0.0001) were positively associated with delayed-late venous phase cortical vein filling. Delayed-late venous phase cortical vein filling was independently associated with poor baseline collateral status (75% vs. 15%, p <= 0.0001; OR = 14.38; 95% CI = (4.33, 47.8); p <= 0.0001). Delayed-late venous phase cortical vein filling is frequently seen in patients with acute ischemic stroke and is associated with poor baseline collateralization.
|
|
