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- Bernson, Elin, 1987, et al.
(författare)
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Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia
- 2018
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Ingår i: Cancer Immunology Research. - : American Association for Cancer Research (AACR). - 2326-6066 .- 2326-6074. ; 6:9, s. 1110-1119
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Tidskriftsartikel (refereegranskat)abstract
- Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to affect favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The impact of CMV infection and adaptive-like NK cells on relapse and survival of patients with AML not receiving allo-SCT remains unknown. We assayed CMV IgG serostatus to determine past CMV infection in 81 nontransplanted AML patients who were receiving relapse-prevention immunotherapy comprising histamine dihydrochloride and low-dose interleukin-2 (HDC/IL2; NCT01347996). CMV seropositivity correlated negatively with leukemia-free and overall survival of patients receiving HDC/IL2, but did not correlate with outcomes in a contemporary control cohort. Analysis of outcome after stratification of patients based on concordant or discordant killer immunoglobulin-like receptor (KIR) and HLA genotypes implied that the negative impact of CMV seropositivity was restricted to patients lacking a ligand to inhibitory KIRs (iKIR). Previous CMV infection was also associated with fewer NK cells expressing only nonself iKIRs (NS-iKIR). We propose that CMV-driven NK cell education depletes the population of NS-iKIR NK cells, which in turn reduces the clinical benefit of relapse-preventive immunotherapy in AML.
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- Johansson, Junko, 1989, et al.
(författare)
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Presence of tumor-infiltrating CD8(+) T cells and macrophages correlates to longer overall survival in patients undergoing isolated hepatic perfusion for uveal melanoma liver metastasis
- 2020
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Ingår i: OncoImmunology. - : Informa UK Limited. - 2162-402X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Uveal melanoma is a malignant tumor of the eye that often metastasizes to the liver conferring poor prognosis. When comparing immune profiles in peripheral blood of untreated patients with uveal melanoma liver metastasis and healthy blood donors, it was observed that immune cells of uveal melanoma patients carried immunosuppressive features. Patient blood contained an increased content of CD14(+)HLA-DR-/low M-MDSCs and inflammatory CD16(+) monocytes, while their dendritic cells expressed lower levels of activation markers. Melanoma patients also harbored an enhanced fraction of CD4(+)Foxp3(+) regulatory T cells, while their effector T cells expressed lower levels of the activation marker HLA-DR. Biopsies from liver metastases were obtained from patients with uveal melanoma that subsequently underwent hyperthermic isolated hepatic perfusion (IHP) with melphalan. There were trends indicating a positive correlation between a high infiltration of CD8(+) T cells in metastases and an activated immune cell profile in blood. High metastatic infiltration of CD8(+) T cells and CD68(+) macrophages, but not of immunosuppressive CD163(+) macrophages, correlated to a longer overall survival in patients treated with IHP. Hence, while the immune system of patients with uveal melanoma shows signs of immunosuppression, the presence of activated immune cells may correlate to a longer survival, at least following IHP treatment.
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- Lundberg, J F, et al.
(författare)
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Dopamine or norepinephrine infusion during thoracic epidural anesthesia? Differences in hemodynamic effects and plasma catecholamine levels.
- 2005
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Ingår i: Acta Anaesthesiol Scand. - : Wiley. - 0001-5172. ; 49:7, s. 962-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During thoracic epidural anesthesia, an intravenous dopamine infusion augments the systemic pressure response and modifies plasma catecholamine levels. If such an altered response occurs when norepinephrine is infused is not clear. Therefore, dopamine and norepinephrine induced circulatory and catecholamine responses were studied before and during thoracic epidural anesthesia. METHODS: Nine chloralose-anesthetized dogs were equipped with thoracic epidural catheters. Dopamine (5, 10, and 20 microg kg(-1) min(-1)), and norepinephrine (0.1, 0.25, and 0.5 microg kg(-1) min(-1)) were infused before and during epidural anesthesia, while cardiovascular performance and plasma catecholamine changes were studied. RESULTS: Thoracic epidural anesthesia decreased arterial pressure, and cardiac contractility. The systemic pressure response induced by dopamine was augmented during epidural anesthesia. Norepinephrine did not increase arterial pressure and myocardial contractility as markedly as dopamine, and cardiac output was not altered. Thoracic epidural anesthesia attenuated the plasma norepinephrine level. Plasma dopamine levels were augmented by the dopamine infusion during epidural anesthesia, while plasma norepinephrine levels were attenuated. In contrast, norepinephrine augmented the plasma norepinephrine levels during epidural anesthesia. In general, plasma norepinephrine levels were three to six times higher during a norepinephrine infusion compared to a dopamine infusion. CONCLUSION: The cardiovascular response to a graded dopamine infusion is augmented during thoracic epidural anesthesia, while norepinephrine-induced effects are unaltered. The modified plasma catecholamine levels may contribute to the hemodynamic differences between dopamine and norepinephrine infusions during thoracic epidural anesthesia.
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- Martner, Jan, 1946, et al.
(författare)
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Apnoea and bradycardia from submersion in "chronically" decerebrated cats.
- 1977
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Ingår i: Acta physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 101:4, s. 476-80
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Tidskriftsartikel (refereegranskat)abstract
- In "chronically" but not in acutely decerebrated cats, submersion of the head caused apnoea and marked bradycardia, associated with a maintained or slightly raised arterial pressure. Since these reflex adjustments, though very reproducible, occurred with a varying latency and could be induced also by nasal injection of water, they appeared to be, at lest in part, elicited from the upper respiratory passages. Thus, a terrestrial mammal, reputed to shun any form of immersion, can exhibit adjustments during head submersion, similar to those in habitually diving species. This response pattern is basically organized at the lower brainstem level.
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- Nielsen, Niklas, et al.
(författare)
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Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design
- 2012
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 163:4, s. 541-548
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Tidskriftsartikel (refereegranskat)abstract
- Background Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32 degrees C to 34 degrees C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. less thanbrgreater than less thanbrgreater thanMethods The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33 degrees C or 36 degrees C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. less thanbrgreater than less thanbrgreater thanDiscussion The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
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- Strand, Kristian, et al.
(författare)
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Variations in the length of stay of intensive care unit nonsurvivors in three scandinavian countries
- 2010
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Ingår i: CRITICAL CARE. - : BioMed Central. - 1466-609X .- 1364-8535. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The length of stay (LOS) in intensive care unit (ICU) nonsurvivors is not often reported, but represents an important indicator of the use of resources. LOS in ICU nonsurvivors may also be a marker of cultural and organizational differences between units. In this study based on the national intensive care registries in Finland, Sweden, and Norway, we aimed to report intensive care mortality and to document resource use as measured by LOS in ICU nonsurvivors. Methods: Registry data from 53,305 ICU patients in 2006 were merged into a single database. ICU nonsurvivors were analyzed with regard to LOS within subgroups by univariate and multivariate analysis (Cox proportional hazards regression). Results: Vital status at ICU discharge was available for 52,255 patients. Overall ICU mortality was 9.1%. Median LOS of the nonsurvivors was 1.3 days in Finland and Sweden, and 1.9 days in Norway. The shortest LOS of the nonsurvivors was found in patients older than 80 years, emergency medical admissions, and the patients with the highest severity of illness. Multivariate analysis confirmed the longer LOS in Norway when corrected for age group, admission category, sex, and type of hospital. LOS in nonsurvivors was found to be inversely related to the severity of illness, as measured by APACHE II and SAPS II. Conclusions: Despite cultural, religious, and educational similarities, significant variations occur in the LOS of ICU nonsurvivors among Finland, Norway, and Sweden. Overall, ICU mortality is low in the Scandinavian countries.
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- Törnell, Andreas, 1994, et al.
(författare)
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CYBA allelic variants are associated with severity and recovery in Guillain-Barré syndrome
- 2023
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Ingår i: Journal of the peripheral nervous system. - 1085-9489. ; 28:3, s. 407-414
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent Campylobacter jejuni infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22phox) on acute severity, axonal damage, and recovery in adult GBS patients. Methods: Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within CYBA using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years. Results: CYBA genotypes linked to reduced formation of ROS, i.e. rs1049254/G and rs4673/A, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying CYBA alleles associated with high formation of ROS. Interpretation: These findings implicate NOX-derived ROS in GBS pathophysiology and CYBA alleles as biomarkers of severity.
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