| 1. |
- Obers, Niels A., et al.
(författare)
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Quantum gravity phenomenology at the dawn of the multi-messenger era—A review
- 2022
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Ingår i: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410 .- 1873-2224. ; 125
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Forskningsöversikt (refereegranskat)abstract
- The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.
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| 2. |
- Abolhassani, H, et al.
(författare)
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Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1032358-
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Tidskriftsartikel (refereegranskat)abstract
- The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.
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| 3. |
- Pang, Ian, et al.
(författare)
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Letermovir prophylaxis for cytomegalovirus reactivation in allogeneic hematopoietic cell transplant recipients : Single center Canadian data
- 2024
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Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 112:2, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes.Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV-seropositive and met criteria for high risk of CMV reactivation.Results: Median start of letermovir was 21 days post-alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p < .001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p = .54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p = .69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p = .27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR.Conclusions: Letermovir prophylaxis started at day +21 post-alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes.
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| 4. |
- Carreira, Abel Santos, et al.
(författare)
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Bloodstream Infections and Outcomes Following Allogeneic Hematopoietic Cell Transplantation : A Single-Center Study
- 2022
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 28:1, s. 50.e1-50.e8
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the single-center incidence and risk factors for bloodstream infections (BSIs) in 651 adults who underwent allogeneic hematopoietic cell transplantation (alloHCT) between 2015 and 2019 and explored the impact of these BSIs on post-transplantation outcomes. Antibiotic prophylaxis with ciprofloxacin was given during the aplastic phase. Overall, the median patient age was 57 years, 79.7% of patients received an alternative donor graft, and 68.7% received post-transplantation cyclophosphamide (PTCy) as part of their graft-versus-host disease (GVHD) prophylaxis. Of the 651 patients, 358 (55.0%) had at least 1 episode of BSI, and the overall mortality rate secondary to this complication was 7.5% (12.6% among those diagnosed with at least 1 episode of BSI). BSI was more often diagnosed during the first 30 days (58.7%), and gram-positive bacteria were the most prevalent microorganisms isolated during the entire post-transplantation follow-up (62%). A high Disease Risk Index (hazard ratio [HR], 1.47; P < .029) and receipt of PTCy-based GVHD prophylaxis (HR, 3.33; P < .001) were identified as risk factors for BSI. Additionally, univariate analysis showed that patients diagnosed with a BSI during post-transplantation follow-up had worse overall survival (HR, 2.48; P < .001) and higher nonrelapse mortality (HR, 2.68; P < .001) than those without BSI. In conclusion, alloHCT recipients with a BSI had a higher risk of mortality compared with those who did not develop BSI. The inclusion of PTCy as part of GVHD prophylaxis was identified as an independent risk factor for BSI during early post-transplantation follow-up. Single-center analyses focused on reporting the incidence and risk factors for BSI highlight the need for active implementation of preemptive strategies to decrease BSI incidence in the alloHCT setting.
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| 5. |
- Carreira, Abel Santos, et al.
(författare)
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Interaction Between High-Dose Intravenous Busulfan and Post-Transplantation Cyclophosphamide on Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplantation
- 2023
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 29:9, s. 581.e1-581.e8
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo- hematopoietic stem cell transplantation. Two hundred fifty-two (26.5%) patients received myeloablative conditioning regimens, and 81.4% received high-dose intravenous busulfan (HD Bu). Six hundred ninety-five (72.4%) patients received post-transplantation cyclophosphamide (PTCY)-based prophylaxis, and 91.4% additionally received anti-thymocyte globulin (ATG) and Cyclosporine A (CsA) (PTCY-ATG-CsA). Two hundred twenty-eight (23.8%) patients developed HC. The day 100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (hazard ratio [HR] = 1.97, P = .035), and HD BU combined with ATG-PTCY-CsA increased this 4 times (HR = 4.06, P < .001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV acute graft-versus-host disease and grade 2-4 HC (HR = 2.10, P < .001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year overall survival (HR = 1.51, P = .009) and higher non-relapse mortality (HR = 2.31, P < .001), and patients with BK-NEG grade 2-4 HC had comparable post-transplantation outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased 4-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory because its presence significantly increases the risk for mortality.
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| 6. |
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| 7. |
- Novitzky‐Basso, Igor, et al.
(författare)
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Anti‐thymocyte Globulin and Post‐Transplant Cyclophosphamide do not abrogate the inferior outcome risk conferred by human leukocyte antigen‐A and ‐B mismatched donors
- 2022
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 108:4, s. 288-297
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Tidskriftsartikel (refereegranskat)abstract
- In donor selection for allogeneic stem cell transplant, several factors are considered for potential impact on transplant outcome. Previous publications suggested single HLA-mismatched unrelated donors (MMUD) may be equivalent to 10/10 matched unrelated donors (MUDs). We retrospectively examined factors affecting outcome in a single-center study using ATG followed by post-transplant cyclophosphamide, termed ATG-PTCy, GvHD prophylaxis. Fifty-two patients who received grafts from MMUD and 188 patients transplanted from MUD between January 2015 and December 2019, at Princess Margaret Cancer Centre, Canada, were enrolled. All patients received reduced-intensity conditioning. Overall survival for 9/10 recipients at 2 years was significantly worse, 37.2% versus 68.5% for 10/10 MUDs, p < .001, as were NRM at 1 year 39.5% versus 11.7%, p < .001, and GRFS at 2 years 29.8% versus 58.8%, p < .001, respectively, potentially due to higher incidence of infections including CMV. By multivariable analysis, factors correlating with survival negatively were DRI, and MMUD, whereas for NRM MMUD and increasing age were unfavorable. For GRFS significant unfavorable factors included donor age ≤32 years, female donor to male recipient, DRI high-very high and MMUD. These data suggest that MMUD, primarily HLA-A and HLA-B MMUD, confer significantly inferior outcome despite use of ATG-PTCy. Further development of novel conditioning regimens and GvHD prophylaxis is needed to mitigate these risks.
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| 8. |
- Novitzky‐Basso, Igor, et al.
(författare)
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Anti‐thymocyte globulin and post‐transplant cyclophosphamide predisposes to inferior outcome when using cryopreserved stem cell grafts
- 2021
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Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:1, s. 61-72
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Tidskriftsartikel (refereegranskat)abstract
- During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.
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| 9. |
- Pereira, Mariana Pinto, et al.
(författare)
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Choosing Between Older Matched Sibling Donor and Younger Matched Unrelated Donor in Allogeneic Hematopoietic Cell Transplantation : Comparison of Clinical Outcomes in Acute Myeloid Leukemia and Myelodysplastic Syndrome
- 2023
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 29:11
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Tidskriftsartikel (refereegranskat)abstract
- The choice between an older matched sibling donor (MSD) and a younger matched unrelated donor (MUD) in allogeneic hematopoietic cell transplantation (HCT) remains a subject of ongoing debate. In this single-center retrospective study of 377 patients who received peripheral blood stem cell (PBSC) transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), we compared outcomes of 85 patients who received grafts from MSDs age >60 years and 292 patients who received grafts from MUDs age <30 years. Compared to recipients of MSD transplants, recipients of MUD transplants were younger and more likely to receive dual T cell depletion (TCD), a higher CD34(+) cell dose, and a fresh graft. Recipients of MSD transplants were maintained on immunosuppressive therapy longer than those who received MUD grafts. We found no differences in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free and relapse-free survival, nonrelapse mortality, relapse, engraftment, graft failure, and acute GVHD between recipients of MSD grafts and recipients of MUD grafts. We report a higher 30-day incidence, but not 1-year incidence, of bloodstream infections among recipients of MUD transplants compared to subjects who received their grafts from a MSD. The incidence of moderate-severe chronic GVHD was higher in MSD graft recipients compared with MUD graft recipients in univariate analysis, but not in multivariate analysis. Although this difference could reflect the greater use of dual TCD, known to be associated with very low rates of chronic GVHD in MUD transplant recipients, the incidence of moderate-severe chronic GVHD was no different between MSD and MUD transplant recipients following propensity score matching, suggesting that other variables could be responsible. Taken together, our data suggest that in patients with AML or MDS who receive PBSC transplants, such factors as convenience, ease of access, and costs should be considered when selecting an older MSD over a younger MUD.
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| 10. |
- Ruperto, N., et al.
(författare)
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The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus : prospective validation of the definition of improvement
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 55:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.RESULTS: The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.CONCLUSION: PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.
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